No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
When winning is everything
Abstract
In the heat of competition, executives can easily become obsessed with beating their rivals. This adrenaline-fueled emotional state, which the authors call competitive arousal, often leads to bad decisions. Managers can minimize the potential for competitive arousal and the harm it can inflict by avoiding certain types of interaction and targeting the causes of a win-at-all-costs approach to decision making. Through an examination of companies such as Boston Scientific and Paramount, and through research on auctions, the authors identified three principal drivers of competitive arousal: intense rivalry, especially in the form of one-on-one competitions; time pressure, found in auctions and other bidding situations, for example; and being in the spotlight--that is, working in the presence of an audience. Individually, these factors can seriously impair managerial decision making; together, their consequences can be dire, as evidenced by many high-profile business disasters. It's not possible to avoid destructive competitions and bidding wars completely. But managers can help prevent competitive arousal by anticipating potentially harmful competitive dynamics and then restructuring the deal-making process. They can also stop irrational competitive behavior from escalating by addressing the causes of competitive arousal. When rivalry is intense, for instance, managers can limit the roles of those who feel it most. They can reduce time pressure by extending or eliminating arbitrary deadlines. And they can deflect the spotlight by spreading the responsibility for critical competitive decisions among team members. Decision makers will be most successful when they focus on winning contests in which they have a real advantage--and take a step back from those in which winning exacts too high a cost.
... Research to-date shows that the desire to win, heightened by competitive arousal, and time pressures associated with auctions have a significant impact on bidding behaviours (Malhotra et al. 2008). This often causes bidders to focus on beating their opponents rather than maximising their profit, resulting in overbidding (Malhotra et al. 2008). ...
... Research to-date shows that the desire to win, heightened by competitive arousal, and time pressures associated with auctions have a significant impact on bidding behaviours (Malhotra et al. 2008). This often causes bidders to focus on beating their opponents rather than maximising their profit, resulting in overbidding (Malhotra et al. 2008). Note though that the aforementioned studies focused on ascending auction formats, and it is yet unknown whether and to what extent these effects come into play in descending auctions such as Dutch auctions. ...
... In post testing interviews, some participants reported they were excited by the competitive nature of the task. Future research may look into physiological measures, to assess arousal and how it affects bidding behaviour (a-la Malhotra et al. 2008). ...
In a Dutch auction, an item is offered for sale at a set maximum price. The price is then gradually lowered over a fixed interval of time until a bid is made, securing the item for the bidder at the current price. Bidders must trade-off between certainty and price: bid early to secure the item and you pay a premium; bid later at a lower price but risk losing to another bidder. These properties of Dutch auctions provide new opportunities to study competitive decision-making in a group setting. We developed a novel computerised Dutch auction platform and conducted a set of experiments manipulating volatility (fixed vs varied number of items for sale) and price reduction interval rate (step-rate). Triplets of participants ( $$N=66$$ N = 66 ) competed with hypothetical funds against each other. We report null effects of step-rate and volatility on bidding behaviour. We developed a novel adaptation of prospect theory to account for group bidding behaviour by balancing certainty and subjective expected utility. We show the model is sensitive to variation in auction starting price and can predict the associated changes in group bid prices that were observed in our data.
... In electronic auctions, only one bidder can win the auction while all others lose (Malhotra, Ku, & Murnighan, 2008). Hence, electronic auctions are characterized by an inherent "social competition" (Delgado et al., 2008(Delgado et al., , p. 1849. ...
... Hence, electronic auctions are characterized by an inherent "social competition" (Delgado et al., 2008(Delgado et al., , p. 1849. During the auction process, this social competition causes increased overall arousal and a "desire to win" (Malhotra et al., 2008). The immediate emotions triggered in response to winning or losing an auction are usually referred to as the joy of winning and the frustration of losing, respectively (Astor et al., 2013;Delgado et al., 2008;Ding et al., 2005) 3 . ...
... Thus, winner regret, loser regret, and the winner's curse are negligible in our study. 4 Here, we assume that winning an auction is related to emotions with positive valence and that losing an auction is related to emotions with negative valence ( Previous research has demonstrated that, due to such interpersonal comparisons (i.e., the "social nature of auctions"; van den Bos et al., 2008), utility derived from succeeding in peer competition may even outweigh the monetary incentives (Cooper & Fang, 2008), which eventually causes auction participants to overbid and pay more for an item than it is actually worth to them (Malhotra et al., 2008). In this sense, high agency causes market interaction to be seen as a "play-to-win game" (Stafford & Stern, 2002, p. 44) 5 in which "people enjoy winning-especially against their rivals-even at a price" (Malhotra et al., 2008, p. 80). ...
The presence of computerized agents has become pervasive in everyday live. In this paper, we examine the impact of agency on human bidders’ affective processes and bidding behavior in an electronic auction environment. In particular, we use skin conductance response and heart rate measurements as proxies for the immediate emotions and overall arousal of human bidders in a lab experiment with human and computerized counterparts. Our results show that computerized agents mitigate the intensity of bidders’ immediate emotions in response to discrete auction events, such as submitting a bid and winning or losing an auction, as well as the bidders’ overall arousal levels during the auction. Moreover, bidding behavior and its relation to overall arousal are affected by agency: whereas overall arousal and bids are negatively correlated when competing against human bidders, this relationship is not observable for computerized agents. In other words, lower levels of agency yield less emotional behavior. The results of our study have implications for the design of electronic auction platforms and markets that include both human and computerized actors.
... This may increase the pressure to raise the stakes and continue with brinkmanship behavior. When adversaries feel that they must win at all costs, participants experience heightened emotions and this can lead to poor decisions (Malhotra, Ku, & Murnighan, 2008). In their study of hypercompetitive environments such as auctions, Massimo and Zaldokas (2016) find that time pressures force decisions to be taken quickly and lead to an over reliance on simple heuristics. ...
... Another direction for future research is to investigate whether the understanding of organizational brinkmanship developed in this article is appropriate for other types of organizations such as large, publicly listed companies with diverse top management teams and diffuse ownership, or how organizational brinkmanship plays out in social ventures driven by a strong ideological purpose if key actors perceive this purpose to be threatened. Engaging in organizational brinkmanship is likely to incur costs for a family firm irrespective of whether a final resolution is satisfactory or not (Henderson, 1967;Malhotra et al., 2008;Smith, 2016). This is because it consumes resources and diverts focus away from the business. ...
The role of brinkmanship in politics and international affairs has captured headlines and popular attention around the globe. It is a behavioral phenomenon whereby to gain concessions actors like states and governments take actions that may not only harm their adversaries, but also themselves. However, hidden from view, and far less understood is its role in business and management. This is an important oversight not only because stakes can be high in business, but also because how members of a firm's dominant coalition respond to existential threats can be critical for organizational outcomes. We introduce the notion of organizational brinkmanship and outline how the process unfolds in a context where family engagement in the business can also serve to heighten potential stakes. With our focus on family business we unravel circumstances where the propensity to maintain historical and current family control over the business can increase susceptibility to engaging in organizational brinkmanship. The cornerstone of our contribution is to develop a conceptual model that explains how the process of brinkmanship can unfold in a family business. We also offer a future research agenda to guide scholarly attention on this important yet under-explored area of research and suggest propositions. This work is particularly timely in light of increasing environmental instability around the globe.
... Similarly, action visibility to external observers may affect the nature of their relationship with firm performance. For example, highly visible actions may provoke swift and meaningful competitive responses (Malhotra, Ku, & Murnighan, 2008), as competitors might respond via actions of their own, reducing value generated and captured from such actions. Last, firms do not act in a vacuum, and an action's degree of conformity to social and institutional norms may affect its performance (Deephouse, 1999). ...
... One potential reason is that many leveraging actions are highly visible to outsiders. As a result, they may provoke swift and meaningful competitive responses (Malhotra et al., 2008), as competitors might respond via leveraging actions of their own (e.g., entering similar markets or developing aggressive marketing campaigns). By doing so, competitors can reduce a firm's ability to extract substantial value from such actions (Coff, 1999). ...
Understanding why some firms outperform others is central to strategy research. The resource-based view (RBV) suggests that competitive advantages arise due to possessing strategic resources (i.e., assets that are valuable, rare, nonsubstitutable, and inimitable), and researchers have extended this logic to explain performance differences. However, RBV is relatively silent about the actions managers could use to create or capitalize on a resource-based advantage. Enriching RBV, the resource orchestration framework describes specific managerial actions that use such resources to realize performance gains. After reviewing the conceptual evolution of these two literature streams as well as related streams, we use meta-analytic structural equation modeling to aggregate evidence from 255 samples involving 111,614 observations to answer outstanding research questions regarding the strategic resources–actions–performance pathway. The results show strong complementarity and interdependence between their logics. Additional inquiry drawing on their complementarity is a clear path toward enhancing scholars’ understanding of how and why some firms outperform others. We build on our findings to lay a foundation for such inquiry, including a call for theorizing centered on the interdependence of resources and actions, as well as new theoretical terrain that can help resource-based inquiry continue to evolve.
... In the public sector, these outcomes can also be budgets, agreed policies, price points or concessions. Intangible outcomes are for instance the felt need to win or have the upper hand in negotiations (Malhotra, Ku, & Murnighan, 2008) or to keep a good reputation for constituents or opponents (Tinsley, O'Connor, & Sullivan, 2002). ...
... This in turn could put private sector negotiators at a strategic disadvantage. Negotiation literature has for example focused on contextual factors such as time pressure and the way it impacts how negotiators make decisions and thus what negotiation outcomes are achieved (Malhotra et al., 2008). Other contextual factors that have been studied are cultural aspects of organizations and the effect of the differences in ideologies when negotiators are from various countries (Salacuse, 1988). ...
Negotiation knowledge is primarily based on research that focuses on the private sector. However, in the public sector, employees from the EU, ministries and municipalities negotiate with the private sector and, for instance, railway companies. As the public and private sector are known to differ in terms of employee aims and behaviour, this research studies if and the extent to which negotiation outcomes differ when these negotiations are carried out by public sector versus private sector-oriented individuals.
The results show that individuals oriented towards the public sector behave more cooperatively in negotiations. Moreover, accountability – a central mechanism in democracies - results in lower negotiation outcomes, while the reduced discretion for public sector negotiators means that outcomes differ. The individual differences between public and private sector negotiators are reduced by contextual factors such as when negotiators are held accountable.
... The question of which type of experience can best help people to learn to address competitive escalation situations is therefore of both practical and economic relevance, as such situations occur frequently in the strategic and competitive environments in which managers operate (Malhotra et al., 2008). Finding cheaper and more efficient ways of learning can help organizations and society to reap the benefits of competition, without paying the costs. ...
... The purpose of Experiment 1b was thus to underline the external validity of the paradigm by replicating some of the results from Experiment 1a with experienced executives, who are typically embedded in competitive environments (Garcia & Tor, 2007;Malhotra et al., 2008). ...
Competitive escalation occurs frequently in managerial environments, when decisions create sunk costs and decision makers compete under time pressure. In a series of experiments using a minimal dollar auction paradigm, we test interventions to prevent competitive escalation. Without any intervention, most people, including experienced managers, escalate and lose money by bidding more than the price is worth (e.g., more than 10 € for 10 €). We test several interventions, in which we provide individuals with different types of experience: direct experience in structurally identical and in structurally similar situations, as well as direct experience in similarly competitive situations (lacking the escalation dimension). We also study indirect experience based on vicariously learning about the situation's consequences (experienced by others) and based on mental simulation by setting oneself a limit regarding where to exit the competition. In 3 experiments (N = 1,229), we find that direct experience in exactly the same or a structurally similar situation allows individuals to prevent subsequent escalation, whereas direct experience in a similar situation without escalation does not. Indirect experience based on vicarious learning successfully reduces competitive escalation, whereas a goal‐setting intervention that has proven instrumental in reducing classic escalation of commitment is not effective. This pattern of variation in the effectiveness of different interventions is consistent with the theory of a hot‐cold empathy gap that prevents people from anticipating how they will experience a competitive situation before entering it. As a methodological contribution, we developed a deception‐free computer‐player dollar‐auction for online participants and a dynamic chicken game.
... In addition, because this competitiveness stems from a motivation to deny the superior knowledge of the advisor, it is likely to be associated with an increase in confidence on the part of the decision maker. Previous research has found that competitive arousal increases decision biases, such as feelings of optimism and illusions of control (Ku, Malhotra, & Murnighan, 2005;Malhotra, Ku, & Murnighan, 2008). Similarly, we expect that competitive arousal felt by high power individuals will increase optimism and illusions of control, leading to greater feelings of confidence. ...
... This type of reassurance could occur by training advisors to affirm the knowledge and experience of the decision maker as a step to making their advice more impactful. At the same time, the goal of diminishing feelings of competitiveness could also be accomplished by choosing decision makers who are relatively more self-assured and who feel the effects of competitive arousal less acutely (Malhotra et al., 2008). ...
Existing research provides considerable insight into what motivates people to seek and use advice. However, we know surprisingly little about what motivates people to give advice. In this paper, we examine the relationship between the psychological experience of power and the practice of giving advice to others. We argue that the psychological experience of power leads individuals to feel more competent relative to those around them and also motivates them to demonstrate that superior competence by providing advice. At the same time, the very act of demonstrating superior competence through advice giving sustains individuals’ psychological experience of power. Thus, the psychological experience of power and the provision of advice are mutually reinforcing phenomena. Three laboratory experiments and one field study provide support for our hypotheses. We discuss implications for theory and practice.
... The question of which type of experience can best help people to learn to address competitive escalation situations is therefore of both practical and economic relevance, as such situations occur frequently in the strategic and competitive environments in which managers operate (Malhotra et al., 2008). Finding cheaper and more efficient ways of learning can help organizations and society to reap the benefits of competition, without paying the costs. ...
... The purpose of Experiment 1b was thus to underline the external validity of the paradigm by replicating some of the results from Experiment 1a with experienced executives, who are typically embedded in competitive environments (Garcia & Tor, 2007;Malhotra et al., 2008). ...
Escalation of commitment, the tendency to increase one’s investment in a losing course of action even after negative feedback is well known for its adverse consequences. In this paper, we investigate a situation in which escalation of commitment occurs in the context of competitive settings. Based on Shubik’s (1971) original game, we introduce a ‘minimal’ dollar auction paradigm, which allows us to study competitive escalation in small anonymous groups in the lab. In three experiments, students and experienced executives bid more than 10 CHF for a prize of 10 CHF. In addition, we test two interventions to prevent competitive escalation: a ‘goal setting’ intervention, which has been successful in reducing classic escalation of commitment, is not effective in the competitive situation, whereas a ‘vicarious learning’ intervention prevents escalation successfully. The result is consistent with the assumption/theory of a cold-hot ‘empathy gap’, which impedes individuals from correctly anticipating their experience of the competitive situation before entering it.
... Individuals who do not perceive themselves as being competitive may consider the characteristic as either genetic or, simply, annoying, but it is physically driven by an adrenaline-fuelled emotional state known as competitive arousal. A review of case studies in which overbidding at auctions was analysed, participants acknowledged that the decision to overbid, or to stop bidding, was made not from data but from the emotional state from which their bids made (Malhotra, Ku & Murnighan, 2008). Though self-perception may not exist during the competitive event itself, the fundamental desire to live is the most common expression of competitiveness found among all (Darwin, 1859;Maslow, 1943). ...
... The increasing arousal caused in a competitive environment, coupled with a decreasing ability to apply and find relative information to make rational decisions, leads to an overreliance on heuristics (Malhotra et al., 2008). Application of a speculative framework to guide decisions results in decisions being made, but not, necessarily, in good decisions being made. ...
... While the optimal outcome for both parties would be cooperation, the inherent distrust and fear of exploitation often lead to scenarios where one or both prisoners betray each other, resulting in suboptimal outcomes for both parties. This also applies to real-world negotiations, where business partners, similarly confronted with uncertain conditions and high stakes [6,7], may resort to unethical negotiation tactics such as false promises, deception, or threats to compensate for potential losses or gains. ...
As the landscape of negotiation ethics continues to evolve, it reflects significant shifts in societal attitudes and organizational priorities. A mere decade ago, the prevailing sentiment toward the legitimacy of unethical negotiation tactics was more lenient, with a common acceptance of occasional lies and deceptions as commonplace. However, the contemporary perspective on this matter is notably more nuanced. As companies increasingly embrace ethical considerations through compliance and corporate social responsibility, the scrutiny of negotiation tactics for their ethical correctness has intensified. To address this societal and, as a consequence, organizational change, our study presents the concept of priming as a strategic tool for promoting ethical conduct in organizational practice. By strategically activating memory content related to ethics, the research seeks to enhance ethical awareness in business negotiations. Through a systematic literature review, the study explores the suitability of different forms of priming in various negotiation contexts and examines practical ways of priming for ethical negotiation behavior. The findings suggest that ethics-based priming in negotiations holds promise for fostering fairness and honesty, presenting viable pathways for integration into negotiation practices.
... Another relevant stream of research concerns the performance and intensity of emotional reactions and emotional arousal (Fisher, 2008;Malhotra et al., 2008). Positive feedback, which is analogous to winning, can increase the overall emotional intensity and arousal (Verbruggen et al., 2017). ...
Peer feedback is often associated with an increase in the contributions of members in online communities. Verbal feedback (such as a review) can give details about how the recipient can improve their contribution, but it requires the recipient to read and process the feedback. Conversely, nonverbal feedback (such as an upvote) is easy to comprehend but does not convey much helpful information. Prior studies have mainly focused on the impact of verbal feedback. However, little has been done to explore the underlying mechanism of the effect of nonverbal peer feedback on people’s tendency to contribute more. We present two experimental studies conducted on Amazon Mechanic Turk. Study 1 demonstrates how verbal and nonverbal feedback impact user contributions differently. Next, building on attribution-emotion-action theory, we use Study 2 to establish a causal mechanism between nonverbal feedback and users’ knowledge contribution. Specifically, users who receive nonverbal peer feedback make internal and external attributions, which in turn impact their emotions and contribution decisions. We find that users receiving more positive feedback attribute this in equal measure internally to perceived self-efficacy and externally to perceived fairness, whereas users who receive negative feedback attribute it more to the lack of perceived fairness of peer feedback. These findings have important implications for both content-sharing platforms and researchers trying to better understand the drivers of online content-sharing behavior.
... Past research has found that performance pressure was positively related to unethical decision-making and conduct: Performance pressure can be perceived by employees as a threat that leads to workplace cheating behavior (Mitchell et al., 2018) and incivility (Jensen et al., 2019;Mitchell et al., 2019). As an important work stressor, performance pressure limits the application of complex cognitive resources, causes employees to have a narrower focus (Fiedler & Garcia, 1987), and results in poor ethical decision-making (Malhotra et al., 2008); in other words, they only focus on meeting performance expectations and pay less attention to other aspects, such as ethical standards. Although previous research has found that performance pressure could be a threat in the workplaces (Mitchell et al., 2019), we know little about whether situational factors (e.g., those related to the supervisor-subordinator relationship) can increase or mitigate this threat appraisal. ...
Drawing on the transactional model of stress and leader-member exchange (LMX) theory, we examine the role of performance pressure in relation to unethical pro-organizational behavior (UPB). We propose that (1) employee perceived performance pressure and LMX interact to increase employees’ willingness to engage in UPB, and (2) employees’ threat appraisal mediates this interaction effect. The results from two studies based on samples of employees in the United States and China supported our theoretical model. We found that LMX moderated the relation between performance pressure and the willingness to engage in UPB, such that the relation was stronger when LMX was high (Study 1). Moreover, the conditional indirect effect (i.e., performance pressure on UPB through threat appraisal with LMX as a moderator at the first stage) was also supported (Study 2). These findings highlight the role of performance pressure and LMX in inducing unethical work behaviors that are aimed at benefiting the organization (i.e., UPB). Theoretical and managerial implications are also discussed.
... Competitiveness triggers individual drive and a desire to excel and win. Research shows that the urge to win is often biological and/or emotional (Malhotra et al., 2008) and that competitiveness can also be an avenue for self-improvement and personal development (Ryckman et al., 1996). Risk-taking refers to taking chances and making investment with uncertain outcomes. ...
Research on entrepreneurial mindset (EM) has proliferated in recent years. Its importance rests on a key assumption: EM matters for entrepreneurial behavior. However, to date, EM conceptualizations remain fragmented, and theories delineating the relationship between EM and the behaviors underpinning entrepreneurship are limited. In this article, we conceptualize EM as a goal orientation formed through dispositional beliefs about entrepreneurship and opportunity beliefs, which results in entrepreneurial behaviors. We draw upon recent advances in entrepreneurial orientation (EO) research at the individual level as a model for dispositional beliefs. Further, we theorize the origins, mechanisms, manifestations, and effect of EM. Finally, we discuss important implications for stake-holders interested in leveraging EM to stimulate entrepreneurial activity and lay out a research agenda for future development of our disposition-based framework.
... Competitiveness triggers individual drive and a desire to excel and win. Research shows that the urge to win is often biological and/or emotional (Malhotra et al., 2008) and that competitiveness can also be an avenue for self-improvement and personal development (Ryckman et al., 1996). Risk-taking refers to taking chances and making investment with uncertain outcomes. ...
Research on entrepreneurial mindset (EM) has proliferated in recent years. Its importance rests on a key assumption: EM matters for entrepreneurial behavior. However, to date, EM conceptualizations remain fragmented, and theories delineating the relationship between EM and the behaviors underpinning entrepreneurship are limited. In this article, we conceptualize EM as a goal orientation formed through dispositional beliefs about entrepreneurship and opportunity beliefs, which results in entrepreneurial behaviors. We draw upon recent advances in entrepreneurial orientation (EO) research at the individual level as a model for dispositional beliefs. Further, we theorize the origins, mechanisms, manifestations, and effect of EM. Finally, we discuss important implications for stakeholders interested in leveraging EM to stimulate entrepreneurial activity and lay out a research agenda for future development of our disposition-based framework.
... There is pronounced heterogeneity with respect to this desire (De Dreu and Boles 1998;Van Lange et al. 1997). The desire to win can lead to bidding more in an auction than the item is worth (Ku, Malhotra, and Murnighan 2005) and to engage in costly litigation rather than settling a case (Malhotra, Ku, and Murnighan 2008). ...
Antitrust authorities all over the world are keen on the presence of a particularly aggressive competitor, a “maverick”. Yet there is a lack of theoretical justification. One plausible determinant of acting as a maverick is behavioral: the maverick derives utility from acting competitively. We test this conjecture in the lab. In a pretest, we classify participants by their social value orientation. Individuals who are rivalistic in an allocation task indeed bid more aggressively in a laboratory oligopoly market. This disciplines incumbents. We conclude that the existence of rivalistic attitudes may justify antitrust policies that protect mavericks.
... Similarly, more recent work on decision making suggests that individuals are less concerned about ethical standards when they judge a situation to be competitive (Butterfield et al. 2000;Messick 1999). This shift in the relative importance of ethical concerns might be attributed to different sorts of affects that are typical for contests characterized by intense rivalry (Kilduff et al. 2016;Malhotra et al. 2008;Pierce et al. 2013). If competition heightens perceived rivalry it is likely to decrease the moral costs of norm violation, if the desire to win lessens the competitors' aversion to using unethical behaviors as a means towards the end of beating the others . ...
Contests are widely used in business contexts because they are believed to increase the effort and performance levels of employees. One negative aspect of contests is that they may provide incentives for unethical behavior aimed at improving one's own position relative to that of competitors. It is therefore important to understand how companies should design contests so as to reduce unethical behavior without reducing the positive effects of contests on employee effort. Research from the social and behavioral sciences can offer relevant insights on this question, as in those fields competition is a subject of sustained academic interest. The aim of this review is to offer a systematic account of the growing literature on contests and unethi-cal behavior and shed light on why and when contests among employees may lead to unethical behavior. To this aim, we also develop a framework for organizing the vast, multidisciplinary literature in a structured and integrative manner. Through this endeavor, our review identifies several directions for future research.
... Performance pressure indicates the expectation that followers must deliver excellent performance outcomes [55,56]. Research on performance pressure has revealed negative consequences, in that it seems to increase poor ethical decision making [55,57,58] and stress [59]. ...
Although prior research has emphasized the disproportional contributions to organizations of charismatic leadership, an emerging line of research has started to examine the potentially negative consequences. In this paper, a theoretical framework was proposed for a study of unethical pro-organization behavior through psychological safety based on social information processing theory, which reveals the detrimental effect that charismatic leadership can have on workplace behavior. To explore this negative possibility, a time-lagged research design was applied for the hypotheses to be verified using 214 pieces of data collected from a service company in China. According to the results, unethical pro-organizational behavior was indirectly influenced by charismatic leadership through psychological safety. Moreover, when employees experienced high performance pressure, charismatic leadership was positively associated with unethical pro-organizational behavior through psychological safety. The implications of these findings were analyzed from the perspectives of charismatic leadership theory and organizational ethical activities to alter the unethical pro-organizational behavior.
... For example, as some people evolve in their prowess of a pursuit becoming highly skilled, such as playing a musical instrument or competing in a sport, society communicates expectations to use these skills instrumentally to earn money and awards (e.g., Smith et al., 2014). Thus, what often drives participation is achieving instrumental ends such as winning a game or completing an art project (Malhotra et al., 2008). We cluster utilitarian views of leisure into groups including using leisure to (a) divert attention from impactful issues, (b) distinguish from and affiliate with certain groups, (c) consume goods, (d) participate in activities, and (e) recuperate from and prepare for work. ...
We provide a critical approach to current colloquial and scholarly understandings of leisure focusing on instrumental understandings of leisure in modern, liberal-democratic society since these instrumental understandings (e.g., diversion, distinction, consumerism, and restoration for work) create confusion about the meaning of leisure. We identify that (a) emphasis on instrumental thinking prevailing in modern society moves people away from embracing leisure as an end with its inherent experiences of meaning and flourishing, and (b) to bring these elements back into leisure, we draw on post-modern, neo-Aristotelian philosophical approaches. We reject the notion of leisure as time or activity and adopt a normative approach identifying leisure as an ethical state of being characterized by authenticity, meaning, and liquidity involving learning as it intertwines with positivity. We provide an account of leisure that builds upon the idea that the good life exists through flourishing, and identify how leisure experiences promote flourishing.
... The max rel transformation subtracts the average outcome of other group members from the personal outcome, the max own transformation ignores the group members' outcomes, and the max joint transformation adds them to the personal outcome (e.g., in the coop game: 5 + 3 × 5 = 20). The investments maximizing subjective outcomes after each transformation in the comp game and the coop game, respectively, are circled in competitive environments (Garcia & Tor, 2007;Malhotra, Ku, & Murnighan, 2008), might have learned to focus on the objective outcome structure of situations and to ignore conflicting situational cues. We decided to combine the data from both studies to test whether results in the ranking condition were comparable. ...
Whether people compete or cooperate with each other has consequences for their own performance and that of organizations. To explain why people compete or cooperate, previous research has focused on two main factors: situational outcome structures and personality types. Here, we propose that—above and beyond these two factors—situational cues, such as the format in which people receive feedback, strongly affect whether they act competitively, cooperatively, or individualistically. Results of a laboratory experiment support our theorizing: After receiving ranking feedback, both students and experienced managers treated group situations with cooperative outcome structures as competitive and were in consequence willing to forgo guaranteed financial gains to pursue a—financially irrelevant—better rank. Conversely, in dilemma situations, feedback based on the joint group outcome led to more cooperation than ranking feedback. Our study contributes to research on competition, cooperation, interdependence theory, forced ranking, and the design of information environments.
... To understand the contextual factors influencing dysfunctional behavior in stores, we first look to the impact of performance pressure on employees. Research on performance pressure has found that it acts as a double-edged sword in that it can motivate employees to perform well (Gardner, 2012a) and be more creative (Rousseau, 1997;Sitkin, See, Miller, Lawless, & Carton, 2011) while also increasing stress and sub-optimal knowledge sharing (Gardner, 2012a) and poor ethical decision making (Malhotra, Ku, & Murnighan, 2008;Mumford et al., 2006). ...
... Similarly, professionals in the sciences perceive production pressure to be the most influential cause of ethical misconduct in scientific work (Goldberg and Greenberg, 1994). Additionally, Malhotra et al. (2008) suggest that poor EDM is likely when people in organisations are pressured to 'win at all costs'. Similar findings have been demonstrated with student samples as well; students' poor EDM increases with competitive pressure (Nill et al., 2004). ...
... Similarly, professionals in the sciences perceive production pressure to be the most influential cause of ethical misconduct in scientific work (Goldberg and Greenberg, 1994). Additionally, Malhotra et al. (2008) suggest that poor EDM is likely when people in organisations are pressured to 'win at all costs'. Similar findings have been demonstrated with student samples as well; students' poor EDM increases with competitive pressure (Nill et al., 2004). ...
... On the one hand, claiming more for oneself yields higher outcomes in the case of success, but on the other hand, the risk of failure is also higher. Following the same line, the competitive arousal model posits that people experience a "desire to win" when dealing with conspecifics, which is fostered by arousal and may hence affect behavior (Ku et al. 2005;Malhotra 2010;Malhotra et al. 2008). The relationship between arousal and behavior was studied for a variety of applications, including financial markets (Lo et al. 2005), electronic auctions Teubner et al. 2015), and negotiation (Druckman and Olekalns 2008). ...
With the proliferation of information technology and artificial intelligence in society, human users have started to engage in social interactions with computer agents. In this study, we conducted a laboratory experiment in which neurophysiological measurements were used to investigate the effect of computer agents on the affective processes and behavior of human negotiators. Participants engaged in alternating-offer bargaining over the partition of a pie with either human or computer counterparts and under different levels of urgency to reach an agreement. Overall, our data show that the subjects claimed significantly higher proportions for themselves when they made opening offers to computer agents than when bargaining with human counterparts, regardless of the degree of urgency in the negotiation. However, when the subjects responded to computer-issued offers the picture was more complex. Whereas under high-level urgency, the subjects were more likely to accept offers made by computer agents than by human counterparts, we observed the opposite effect for low-level urgency, where they were less likely to accept the offers of computer agents. In combination, these behavioral patterns lead to the use of computer agents yielding an increase in economic efficiency. Further, the subjects exhibited less emotionally charged behavior when facing computer agents than when facing human counterparts, as the intensity of affective processes was lower and the relationship between arousal and offer acceptance was observable only when the counterparts were human. The results of our study shed light on the potential benefits and intricacies of employing computer agents in electronic negotiations.
... Negotiations produce outcomes such as agreements or contracts, coalitions or even impasses, which are tangible (Saorínlborra & Carmen, 2006). Intangible outcomes of negotiations are psychological needs such as the individual need to win (Malhotra, Ku, & Murnighan, 2008) or a felt need to keep a good reputation (Tinsley, O'Connor, & Sullivan, 2002). ...
Negotiation is ubiquitous in the public sector, from policy formation to budget allocation or the coordination of public–private partnerships. The focus on negotiations has nevertheless been somewhat limited in public administration research, but in neighboring disciplines such as behavioral economics and social psychology, negotiations have been studied extensively. This chapter aims at filling this gap.This chapter discusses negotiations by focusing on the individual negotiator. I focus on what a negotiation is and who negotiates in the public sector by discussing some substantive examples. Distributive and integrative negotiations are discerned and are accompanied by some public sector illustrations. Specific attention is given to public sector distinctiveness in context and its workers and its potential consequences for negotiations.
... For example, in 1993, Virgin Atlantic won a libel suit against British Airways after the latter admitted to having launched a "dirty tricks" campaign against its rival, which included calling Virgin's customers and lying to them about flight cancellations in addition to circulating rumors that Virgin CEO Richard Branson was infected with HIV (Branson, 1998). In a slightly less scandalous example, Boston Scientific recently overpaid for its acquisition of Guidant -later referred to as "arguably the second-worst" acquisition ever -in large part because it was bidding against rival Johnson & Johnson (Malhotra, Ku, & Murnighan, 2008;Tully, 2006). ...
Abstract We investigate the psychological phenomenon of rivalry, and propose a view of competition as inherently relational, thus extending the literatures on competition between individuals, groups, and firms. Specifically, we argue that the relationships between competitors – as captured by their proximity, relative attributes and prior competitive interactions – can influence the subjective intensity of rivalry between them, which in turn can affect their competitive behavior. Initial tests of these ideas within NCAA basketball indicate that (1) dyadic relationships between teams are highly influential in determining perceptions of rivalry (2) similarity between teams and their histories of prior interactions are systematically predictive of
... Moreover, Ariely and Simonson (2003) conducted a survey among Internet auction participants and found that 76.8% of the respondents perceive the other bidders as "competitors." In this sense, participating in an auction seems to be perceived as a competitive game in which the inherent social competition can cause a strong desire to beat the opponents and experience the uniqueness of being first upon winning (Malhotra et al., 2008;Stafford and Stern 2002). In the light of these results, Engelbrecht-Wiggans and Katok (2007) argued that theories, which build on the social competition of auctions, require inter-personal comparisons and, therefore, necessitate the presence of human opponents. ...
Auction sites on the Internet frequently put bidders under time pressure or highlight the social competition that is inherent to auctions. Both aspects are believed to elicit an exciting shopping experience, which may culminate in auction fever. In two laboratory experiments, we investigate the process of auction fever in retail auctions and demonstrate when and how auction fever affects bidding behavior. In contrast to previous studies, we employ physiological measurements as an objective and continuous assessment of bidders’ arousal in addition to a subjective assessment of bidders’ emotions through psychometric scales. Moreover, we explicitly study the interaction of time pressure and social competition on arousal and bids. We find that bidders’ arousal is increased in high time pressure auctions and that this leads to higher bids in ascending auctions—but only when bidders compete with human opponents. Thus, social competition is the actual driver underlying the auction fever phenomenon. Furthermore, we show that the “joy of winning” is significantly stronger than the “frustration of losing” in ascending auctions. Finally, we discuss the implications of our findings for the design of retail auctions.
... Similarly, Goldberg and Greenberg (1994) found that scientific professionals perceived production pressures to be the most important cause of ethical breeches they had observed in the course of their work. Furthermore, Malhotra, Ku, and Murnigan (2008) suggested that when people in organizations are pressured to "win at all costs," poor EDM is likely to occur. Finally, Nill, Shibrowsky, and Peltier (2004) found that as competitive pressure increases, students' unethical decision making increases. ...
This study examined how the number and types of consequences considered are related to forecasting and ethical decision making. Undergraduate participants took on the role of the key actor in several ethical problems and were asked to forecast potential outcomes and make a decision about each problem. Performance pressure was manipulated by ostensibly making rewards contingent on good problem-solving performance. The results indicated that forecast quality was associated with decision ethicality, and the identification of the critical consequences of the problem and consequences for others were associated with both higher quality forecasts and more ethical decisions. In addition, the identification of a larger number of consequences was negatively associated with ethical decision making. Performance pressure did not impact forecast quality or ethicality of decisions. Theoretical and practical implications of these findings are discussed.
... Here, user representation plays an important role, and most platforms prompt their users to provide some personal information and a profile photo. This may be directed towards fostering social competition (Malhotra et al., 2008) among users and driving end prices, as practiced by some entertainment shopping and auction platforms (e.g., dealdash.com). It also may be targeted at fostering cooperative and benevolent and considerate behaviour (e.g., Airbnb). ...
Sharing spare resources on customer to customer (C2C) web platforms yields economic advantages for users on both supply and demand sides. It also increases resource efficiency by enabling better utilization patterns, which in turn provides societal and environmental benefits. Establishing trust among users is a key factor in facilitating the sharing of resources in such platforms. Among other methods, the use of profile pictures has proven to increase trust in peer-to-peer interactions. However, this comes at a considerable cost of privacy. In this study, we compare different levels of user representations (i.e. picture humanization) in a lab experiment involving 216 users and analyze their effect on users' sharing behaviour on a C2C platform. Our results indicate that an increased level of picture humanization increases users' perception of social presence and decreases their perception of anonymity. In turn, perceived anonymity has a marginal negative impact on users' sharing behaviour while perceived social presence impacts positively users' sharing behaviour through a path that involves trust and perceived reciprocity.
... In situations where decisions with serious or long-term consequences must be made in the heat of the moment or instantly, one often does not reason the way through by carefully reflecting on the best course of action even though decision science does insist that reason is most prudent. The limits of our capacity to jo ann heydenfeldt …, 1/29/2013 7:22 AM Deleted: occurred in process volumes of information are well known (Malhotra & Murnighan, 2008, Thaler, & Sunstein, 2008, Hallinan, 2009, Daft, 2010. Behavioral economist Charles Roxburg (2003) cites eight common flaws in both individual and collective thinking that include 1) overconfidence in accurate estimates and in our own ability 2) accounting decisions based on where the money comes from -if only winnings are lost it is not a real loss, 3) status quo bias in favor of hanging on to what we have, 4) anchoring to previous information -it is dangerous to anchor in the past when the future is completely unrelated to the past, 5) throwing good money after bad -we have a strong aversion to loss, 6) the herding instinct -following the herd or others rather than relying on one's own information and analysis can be almost irresistible , 7) humans are not good at estimating how much pleasure or pain they will feel if circumstances change dramatically, and 8) humans overestimate how much others share their views, beliefs, and experiences leading to a) selective resources confirmation bias -we seek out information that support our own hypothesis, b) selective recall -remembering only the facts that reinforce our assumptions, c) biased evaluation -impute hostile motives to critics and d) group think pressure to agree with others (Roxburg, 2003). ...
Recent neuroscientific research describes how the brain and extended nervous system make decisions. This article depicts current theory as it relates to decision-making strengths, shortcuts, simplifications, biases, and serious data restricting habits of the brain. This information demonstrates that the brain, both individually and collectively, can be a deceptive guide for decision making in emergent situations when information is based on preexisting, subconscious frames of reference. Training is proposed to strengthen conscious information-processing capacity.
... In such situations competitive behavior can hurt the individual [10,12]. The desire to win can overpower original goals based on utility maximation and individuals are often willing to pay more than planned and take profit losses in order to secure the completion of the given task and beat the opponents [5,18]. Hence we theoretically predict the following. ...
This article presents an evaluation approach for alternative electronic market designs and examines the impact of competitive arousal under time pressure on market performance in a group-buying setting. Drawing on theory from economics, decision theory, and information systems, we present a competitive arousal model for a social buying setting that posits that introducing competitive arousal among buyers reduces buyer profits and that social facilitation can mitigate these costs through better task completion and time to completion rates. Using an economic experiment, we found that rivalry has a negative effect on buyer profits but also that competitive arousal increases the efficiency of social facilitation in terms of group formation. We discuss the implications of these results.
... Nevertheless, social desirability is of major concern in laboratory based auctions, as scrutinizing people's bidding behavior in a controlled environment could create a Hawthorne effect , especially when auctioning controversial goods and the targeted audience is female (Norwood and Lusk, 2011) b Auction fever Auction fever induces participants to submit high bids for the sake of winning the auction, i.e. to be the "top dog" (Shogren et al., 2001a;Corrigan and Rousu, 2006a). It is often explained by perceived competition, which is aroused by social facilitation and rivalry (Ku et al., 2005;Malhotra et al., 2008); a quasi-or pseudoendowment effect, due to perceived ownership (Prelec, 1990); or an attachment effect, which refers to a higher expected probability of winning/buying (K+ oszegi and Rabin, 2006;Ehrhart et al., 2008). The nature of experimental auctions (market environment, bidding process, self-reported valuations) makes them not only prone to SDB, but also to auction fever. ...
Purpose - Experimental auctions are widely used as a non-hypothetical value elicitation method to examine consumer preferences for novel, controversial foods. However, despite its advantages over hypothetical methods, its practice might lead to a wide variety of biases. The purpose of this paper is to provide a list of key cognitive biases and design effects in food auction research and to deliver scientifically underpinned procedures in order to assess, control and reduce them. Its applicability and relevance is examined in auctions on willingness-to-pay for folate (GM) biofortified rice.
Design/methodology/approach - Based on auction literature, a list of 18 biases has been developed. Experimental auctions were conducted with 252 women from Shanxi Province, China to test the occurrence of eight biases, while demonstrating measures to reduce the risk of ten biases.
Findings - The results lend support for three information-related effects, i.e. confirmation bias, conflicting product information effects and a primacy bias, but not for a multiple-good valuation effect, a panel size effect, a trial winner effect and time-related sampling biases. Furthermore, there are no clear indications of social desirability bias, auction fever and a false consensus effect.
Research limitations/implications - This study emphasizes the need to take into account, and measure the risk of various biases when developing, organizing and interpreting experimental auctions. Future research should further extend the list of biases and validate the study findings.
Originality/value - By using a highly topical subject, this study is one of the first to address the potential risk of cognitive biases and design effects in experimental (food) auctions.
This chapter explores the dynamic realms of leadership and executive coaching and finds the intersection of the two. It begins by contrasting the traditions of athletic coaching with executive coaching, through the lens of individualism versus collectivism. It identifies the connections between leadership and coaching and introduces the concept of leadership-as-practice (L-A-P), which shifts the perspective to a collective phenomenon. It draws insights from the collectivist approach of athletic coaching to present a novel hybrid framework called gamified leadership coaching (GLC). Coaching, with its focus on skill enhancement, motivation, strategy, and development, has evolved over time, with athletic and executive coaching contributing distinct patterns and methodologies.
The auction literature finds that competition drives price outcomes and has both rational and psychological components. In bubble markets, emotional factors are heightened, potentially impacting on the interaction between the strategic setting of guide prices by auctioneers, competitive bidding and final auction price outcomes, themes not explored in the extant literature. In a real estate bubble, we find evidence that auction prices anchor on guide prices and that any emotional impact on competitive bidding associated with auction fever does not occlude the assimilative role for the guide price as an anchor. Interestingly, however, we find evidence consistent with real estate agents systematically setting guide prices at deep discounts relative to fundamentals, prima facie consistent with a belief in the reversal-of-the-anchoring effect, suggesting their actions may, paradoxically, dampen the effect of the bubble rather than amplify it.
We study pricing in the art auction market, focusing on the impact of color composition in non-figurative paintings on hammer prices and willingness-to-pay, by means of both field and laboratory data. Our field data, consisting of art auction prices, reveal a color hierarchy reflected in hammer prices: a one standard deviation increase in the percentage of blue (red) hue triggers a premium of 10.63% (4.20%). We conducted laboratory experiments in the US, China, and Europe, and elicited participants’ willingness-to-pay and measured emotions. We find that blue and red paintings command a premium: blue (red) paintings generate 18.57% (17.28%) higher bids. Color influences prices through the channel of emotional pleasure rather than arousal. Our results are consistent across all three cultures and independent of individual traits such as gender, risk aversion, education and cultural background.
Process dynamics in developing and implementing business strategies demonstrate a conceptual framework that decomposes the overall acquisition integration process into four sequential and co-evolving processes, which include: formulating the integration logic and performance goals, establishing the integration planning approach, executing operational integration, and executing strategic integration. The concept of process dynamics and process completeness are discussed in this chapter in reference to firms doing business in a competitive marketplace. It is argued that process completeness is achieved when a firm's delivery system synchronizes with the expectations of consumers in the competitive marketplace. The discussions in the chapter guide readers to understand the process dynamics and determine the ways to drive leadership in a competitive business environment.
Hormones exert powerful, but covert, effects on financial decision-making. These vary according to the context of the decision, the type of decision being made and features of the individual making that decision. There are differences, for example, between rapid decisions made under duress (e.g. trading) and more deliberate ones made cooperatively (e.g. management) and those made by trained professional or financial management in everyday life. This chapter focusses mainly on acute decisions. Most studies have been made on males, who have dominated professional finance. Financial decisions involve both cognition and emotion, though the two are not clearly separable. They involve both risk and reward evaluations, and hormones, particularly testosterone, cortisol and oxytocin, influence both. The rewarding function of money has to be learned, and this involves areas of the brain such as the amygdala, which are heavily influenced by steroid hormones. Decisions are influenced not only by reward (utility) but by emotions (e.g. ‘framing’). Stress, and associated levels of cortisol, can impair attention and risk assessment, and levels alter in response to uncertainty; however more prolonged increases may have different effects on risk appetite and impulsivity. Testosterone enhances competitiveness, aggression, risk appetite and optimism in finance as it does in its major role in reproduction. Testosterone levels are also sensitive to winning or losing, and this may affect subsequent decisions. In females, phases of the menstrual cycle alter risk appetite, which is maximal at midcycle. Oxytocin administration increases trust, an essential ingredient of financial transactions. Within each individual, it is the pattern of these hormones, and how they change, that determines the influence they will have on financial decisions, which should not be underestimated, though their roles have received little consideration in the world of finance.
Multiple situational influences are often present in organizational ethical dilemmas. This article explores the influences of recipient of the consequence, performance pressure, and interpersonal conflict on sensemaking processes, metacognitive reasoning strategies, and decision ethicality. Results suggest that decision ethicality is greater when individuals are the recipients of consequences. In addition, individuals analyzed causes of the dilemma to a greater extent when faced with low interpersonal conflict and when consequences occurred at an individual level. Individuals in the low interpersonal conflict condition anticipated consequences, looked within, and considered others more than those in the high interpersonal conflict condition. Additional research on performance pressure is needed given that the manipulation used in this study was not effective. Implications for theory and practice of ethics in organizational settings are discussed.
The final chapter reinforces the power of mentoring as a process of building support and ultimately resilience for the mentee. Ideally, it engenders within the mentee, deep learning to sustain them well beyond their mentoring experience. Processes to ensure the sustainability of mentoring from the strategic to the personal are discussed. The outcome is that the mentee uses mentoring as a springboard to enhance their personal and professional power to make a difference in their life.
The results presented in this paper have been produced as part of an ongoing study to model the impacts of construction documentation incompleteness on claims management. The research project examines both the antecedents (primitive project characteristics of interorganizational relationship (IOR) governance mechanisms, i.e. Uncertainty, Asset Specificity, and Frequency of trade between parties) and consequences (Claims Management, in this case) of governance structure. There is a need to understand governance structure antecedents and consequences to better assist modern project management. This paper reports on development of measures of: the Frequency antecedent and its impacts on the corresponding IOR governance mechanisms developed to manage projects. Due to the sensitive nature of the information required for this research, data collection has been a primary concern throughout. Also, given the dynamism and practical concerns (confidentiality, ease of collection or provision, cost, time, etc.) of the research process, careful consideration has been given to acquiring an appropriate data set which would permit rigorous testing and analysis to address the research questions. Throughout, the aim has been to maximize response rates and quality of data obtained. Therefore, an effort is also made to outline the considerations behind development of clear and precise questions to elicit data and information about the Frequency antecedent and its impacts that was readily available to the respondents (a professional body of construction lawyers).
With the emergence of Internet, there is more and more information disseminating all over this channel. The abundant amount of information, however, causes difficulty for users to locate desired information, which is referred to as the information overload problem due to our limited processing ability. Therefore, recommender systems arise to assist users to acquire useful information based on their past preferences or collaborative preferences from other sources. Group recommendation is the task of recommending items for a group of users who participate in a social activity intentionally or randomly. This kind of research is essential in the circumstances when a group of users participate in such activities as watching movies or TV shows with friends, finding restaurants for dinner with colleagues, and picking books to study in a book club. It notably distinguishes itself from personalized recommendation in that collective group behavior needs to be addressed by taking individuals' behaviors into account. The objective of this research is thus to propose hybrid filtering approaches for group recommendation on documents. Particularly, latent Dirichlet allocation to uncover latent semantic structure in documents is incorporated to serve as a bridge to connect content-based filtering and collaborative filtering as a whole, and generate complementary and additive effects for better performance. Two experiments are conducted accordingly. The results show that our proposed approaches (GCBPF and GSBICF) outperform other traditional group filtering approaches on the recommendation performance, which justifies the feasibility of our proposed approaches in applications.
Increased competition in the global marketplace has created enormous pressure on system implementation, particularly in the field of marketing. Systems Thinking and Process Dynamics for Marketing Systems: Technologies and Applications for Decision Management describes a holistic approach to monitoring, evaluating, and applying appropriate marketing strategies, and understanding the competition and its future implication on the business of a company. As complexities multiply, the scientific concept of systems thinking and analyzing process dynamics explained in this publication allows marketing firms succeed. The critical issues facing firms today are presented in a thoroughly modern context, laying the foundation for a bright future.
This study experimentally examined how power and gender affect negotiation behaviors and how those behaviors affect negotiated outcomes. One hundred and forty-six dyads, in four combinations of power and gender, negotiated compensation agreements. In line with gender stereotypes, male negotiators were more dominating and females more obliging and somewhat more compromising. However, partially challenging the common association of power and masculinity, high-power negotiators were less dominating and more collaborating, obliging and avoiding than their low-power opponents. Generally, feminine and high-power behaviors induced agreement while masculine and low-power behaviors enhanced distributive personal gain. The study also assessed patterns of behavioral reciprocity and used sophisticated analytic tools to control for dyadic interdependence. Therefore it helps to elucidate the negotiation process and the role that power and its interplay with gender play in it.
Auction fever is a frequently observed phenomenon in traditional and Internet auctions. However, traditional approaches of auction theory often neglect the inuence of emotions. In this paper we discuss a unied framework for emotional bidding in auctions and identify challenges for future auction fever research. In particular, we identify interdependent utilities and product characteristics as important inuencing factors for auction fever, which have only gained little attention in the literature at this stage. Further, methodological ap-proaches for auction fever research are discussed. While a substantial part of auction fever literature is based on deception of participants, one has to consider fundamental drawbacks of this approach. In contrast, we nd that applying physiological measurements in economic laboratory experiments and auctioning real world commodities is a promising (complemen-tary) approach. Further, letting subjects compete with computerized agents seems to be an adequate approach for assessing the importance of interdependent utilities.
The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease.
Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice.
Total rheumatoid factor (RF) activity and individual RF isotypes were measured in 62 patients with rheumatic diseases. Retrospective analysis of available x rays showed an association between IgA RF and the occurrence of periarticular bone erosions in hands. In contrast, IgG RF and IgM RF did not show any significant association with erosions. Furthermore, a close correlation was observed between the RF isotype levels in simultaneously drawn serum and synovial fluid samples. The possible significance of IgA RF in the pathogenesis of bone erosions is discussed.
Reappraisal of disease-modifying antirheumatoid drug (DMARD) therapy in rheumatoid arthritis (RA) has raised the possibility that the risks of treatment outweigh the benefits.
To provide more information a retrospective survey of the case-notes of 325 patients with RA was performed. The case-notes were randomly selected from the 2320 RA patients indexed in one department. Improvement was defined by the contemporary written notes of the managing physician. Analysis employed the life-table technique.
A total of 247 case-notes could be adequately analysed: 154 patients had received one or more DMARDs constituting 251 drug-patient exposures. Improvement followed drug-patient exposure in 57% of cases after a delay of between one and seven months Nine per cent occurred within one month and 22% within two months. Of those patients withdrawn from treatment after less than two months, the ‘early withdrawal’ group, 25% subsequently improved without further DMARD therapy. The probability of still receiving a specific DMARD 8 months, 24 months and 36 months after the start of treatment was 50%, 25% and 10%, respectively. The majority of withdrawals resulted from adverse reactions. There was no evidence for a relationship between patient responses to sequential DMARDs.
Cyclosporin A (CsA) is a potent immunosuppressive agent, now gaining wide application in human organ transplantation. The immunosuppressive activity of CsA is at least in part due to inhibition of lymphokine production by activated T lymphocytes. Specifically, inhibition of T-cell growth factor (TCGF; also designated interleukin 2) production appears to be an important pathway by which CsA impairs T-cell function. To define further both the specificity of CsA and the level at which it interferes with lymphokine gene expression, we have studied its effects on TCGF mRNA accumulation as well as TCGF gene transcription. These studies were performed with a cloned human leukemic T-cell line (Jurkat, subclone 32), which can be induced with phytohemagglutinin and phorbol 12-myristate 13-acetate to produce large amounts of TCGF. In these cells, high levels of TCGF mRNA were present in induced but not in uninduced Jurkat cells as judged by hybridization to a cloned human TCGF cDNA probe. CsA completely inhibited induced TCGF mRNA accumulation at concentrations of 0.3-1.0 microgram/ml, whereas low levels of appropriately sized TCGF mRNA were present at 0.01 microgram/ml. In nuclear transcription experiments, CsA inhibited the synthesis of TCGF transcripts in a dose-dependent manner with complete inhibition at a concentration of 1 microgram/ml. In contrast, CsA did not inhibit the expression of two other inducible genes, TCGF receptor and HT-3. Further, HLA gene expression was also less affected than TCGF in CsA-treated cells. These data suggest a relatively selective action of CsA on TCGF gene transcription.
The immunohistology of synovium from a tender, swollen knee and peripheral blood cellular immune function were correlated in 24 clinically similar patients with active, seropositive rheumatoid arthritis who were not taking cytotoxic or long-acting antirheumatic drugs. The patients were classified as anergic (n = 6) or nonanergic (n = 18) on the basis of peripheral blood mononuclear cell proliferative responses to a battery of soluble recall antigens. The peripheral blood mononuclear cells of anergic patients failed to respond significantly to any soluble recall antigen, whereas cells from nonanergic patients responded to at least one such antigen. Multiple pieces of synovial tissue were obtained from each patient at arthroscopy. To minimize intrajoint variability, all pieces were analyzed and averaged to determine a composite profile of abnormalities. Synovial specimens from all six anergic patients had "high intensity" lymphocytic infiltration (group A). In sharp contrast, synovial specimens from 15 of 18 nonanergic patients had "low intensity" lymphocytic infiltration (group B) (P = 0.002). Group A tissues typically showed higher intensity T cell and plasma cell infiltration, more synovial lining layer hyperplasia, more HLA-DR bearing cells, and a higher ratio of Leu 3A/Leu 2A T cells than did group B. Group B tissues had fewer infiltrating cells (most of which were OKM1 and HLA-DR bearing), more extensive fibrin deposition, and far fewer T and plasma cells. Although these data do not imply that synovium from different joints in an individual patient are immunohistologically identical, they do provide evidence that peripheral blood mononuclear cell immune function reflects immunopathologic events in the biopsied joint. Moreover, the data further support the view that clinically active rheumatoid arthritis is, like certain other chronic inflammatory conditions, a heterogeneous disorder with polar subgroups.
Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.
One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.
Cyclosporine (10 mg/kg/day) and azathioprine (2.5–3 mg/kg/day) were compared for 26 weeks in an open, controlled, randomized study of 24 patients with rheumatoid arthritis. Each treatment group consisted of 12 patients. Those patients who took cyclosporine improved significantly in the 50-foot walk time, circumferences of proximal interphalangeal joints, Ritchie articular index, global assessment by investigator, and grip strength, when compared with baseline findings. In the azathioprine group, there was improvement only in grip strength.
One hundred eighty-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 gm/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37—week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.
Seventy-five patients with rheumatoid arthritis (RA) were reviewed 9 years after an extensive evaluation which included quantitative measures of functional capacity. These patients had received multiple intraarticular injections of thiotepa with corticosteroids early in their course, but appear demographically and functionally similar to other RA patients who had not received this therapy. Severe morbidity was seen over the 9-year period in the 55 surviving patients, including significantly lower overall functional capacity in 92% of patients studied, lower grip strength in 93%, and longer button test results in 84%. Work disability occurred in 85% of patients under age 65 who had been working full-time at disease onset. There was increased mortality at the 9-year review, similar to most reported series of RA patients from referral centers; however, a significant increase in neoplasia, which was of concern because of the use of intraarticular thiotepa, was not seen. In terms of functional capacity, including responses to questions about ability to perform activities, walking time, and the button test, those patients who had died prior to review had significantly lower baseline values than did those who survived. Of the 75 patients, 20 had died and 51 had lost significant functional capacity over a 9-year period, documented by quantitative measures of functional capacity.
The incidence of malignant neoplasms among 11,483 male and 34,618 female individuals with rheumatoid arthritis was studied using two separate nationwide data registers covering the whole Finnish population: the Social Insurance Institution's Population Data Register, which includes information on medication for certain chronic diseases, and the Finnish Cancer Registry, with data on all cancer patients diagnosed in Finland. The follow-up comprised a total of 213,911 person-years.The total incidence of all malignant neoplasms was higher in males and on the level expected in females. The expected number of cases of leukemia, lymphomas, Hodgkin's disease and myeloma in both sexes was 59.6 as compared with the 130 cases observed. This difference is statistically highly significant (P < 0.001). The incidence of cancer of the respiratory organs was higher in males, and the incidence of cancer of the rectum and stomach lower than expected in rheumatoid females.
Thirty-one patients with severe rheumatoid arthritis were treated with intravenous perfusion of human placenta-eluted gammaglobulins. These gammaglobulins, which are IgG eluted from placental tissue, have strong immunomodulating properties in vitro. Several clinical trials were tested to find the optimal useful dosage. A 50 percent improvement was considered a good result and was obtained in 60 percent of patients with rheumatoid arthritis. The best results were obtained in patients receiving 1,500 mg daily seven days each month. Six subjects had a long remission of their disease after the end of treatment. The side effects were usually minor. In all patients, an immunostimulation of lymphocyte function was shown, even when they had no improvement. A control group of patients underwent perfusion with IgG from placental blood without any clinical or immunologic effect. It is suggested that the in vivo effects of placenta-eluted gammaglobulins might be mediated by polyspecific anti-HLA-DR antibodies.
The place of sulphasalazine in the management of rheumatoid arthritis over prolonged periods of time has been compared and contrasted with that of sodium aurothiomalate. One hundred and forty-three patients (59 on sulphasalazine, 84 on sodium aurothiomalate) have been treated for periods of up to 42 months. Sulphasalazine is highly effective for some patients, though probably less frequently than sodium aurothiomalate. However, its safety profile is far superior, and very long-term treatment with sulphasalazine is a safe option for treatment of rheumatoid arthritis.
Genes of the major histocompatibility complex, HLA, are associated with susceptibility to rheumatoid arthritis (RA), but the aetiology of this chronic inflammatory disease is not known. Synthetic oligonucleotide DNA probes were constructed to distinguish between two closely related but distinct alleles encoding the HLA-DR4 specificity in patients with RA. With these allele-specific oligonucleotide probes an uncommon DR4 genetic variant, Dw14, was identified in 6 of 7 RA patients homozygous for HLA-DR4. This allele may play an important part in susceptibility to RA.
Outcome of therapy, in terms of functional capacity, radiological measures of joint damage, erythrocyte sedimentation rate (ESR), rheumatoid factor, and mortality, was determined prospectively in 112 consecutive rheumatoid arthritis (RA) patients treated for 20 years at one centre, where a policy of active treatment was pursued with the use of gold, chloroquine, steroids, and, in resistant cases, penicillamine or cytotoxic drugs. By 20 years 35% were dead. Mortality was often attributable to RA. Function improved in the early years of treatment but declined considerably between 10 and 20 years. At 20 years 19% were severely disabled. Radiographs showed related evidence of increasing joint destruction. The ESR and rheumatoid factor levels changed little. Age, late presentation, and rheumatoid factor seropositivity at presentation were poor prognostic factors. The concept of "remission-inducing" drugs is fallacious. Early treatment may be advantageous, but the prognosis of RA is not good.
Ninety patients were entered into a randomized, controlled, double-blind trial lasting 12 months to compare auranofin (6 mg/d), and D-penicillamine (250 mg/d for 4 weeks, 500 mg/d for 4 weeks, then 750 mg/d thereafter) in the treatment of rheumatoid arthritis. Most patients in both groups completed the trial with significant improvement in all quantitative measures of efficacy. Patients treated with D-penicillamine were more likely to have "important improvement" in physician global assessment, swollen joint count, and score and grip strength. The overall frequency of side effects was similar between the two groups; however, more patients were withdrawn for adverse effects from the D-penicillamine group, and proteinuria (greater than or equal to 2+) and thrombocytopenia (less than 100 000 mm3) occurred significantly more frequently with D-penicillamine than auranofin (p = 0.028). These results suggest that in the dosage regimen used, auranofin is safer than D-penicillamine but that D-penicillamine tends to show greater clinical effectiveness in patients with rheumatoid arthritis.
Intraperitoneal administration of group A streptococcal cell walls to rats induces an acute arthritis that resolves and is followed by a chronic lesion. The effect of low dose methotrexate, D-penicillamine and gold thioglucose has been investigated in this model. Whereas D-penicillamine and gold thioglucose had no effect on the hind paw inflammation and joint destruction (radiological assessment) associated with the lesion, methotrexate treatment suppressed both of these variables. Spleen cells derived from cell wall treated arthritic rats were hyporesponsive to concanavalin A (Con-A) and were deficient in the synthesis of interleukin 2 (IL-2). Spleen cells derived from methotrexate treated rats exhibited an improved response to Con-A and their ability to synthesize IL-2 was significantly enhanced.
Twelve patients with refractory rheumatoid arthritis were included in a 1-year open trial of cyclosporin A (CsA), 5 mg/kg/day. Clinical efficacy was observed 1 month after beginning treatment, was well established after 4 months of therapy, and remained stable for the remainder of the 1-year treatment period. Among the numerous side effects observed, renal toxicity and hypertension occurred suddenly during the trial and required constant monitoring, adequate therapy, and modulation of CsA dosage. Cyclosporin A seems to be an effective treatment for active rheumatoid arthritis, but it requires close monitoring for toxicity.
To determine if long-term methotrexate-induced improvement of rheumatoid arthritis is sustained after the drug is discontinued, 10 unselected patients with responses to weekly oral methotrexate given for at least 36 months (mean 40.1) were randomly assigned to receive methotrexate or identical-appearing placebo tablets for two months. After one month, all five patients receiving placebo had to have the study terminated due to a flare of their disease manifested by statistically significant deterioration in multiple clinical parameters. It is concluded that patients receiving long-term methotrexate must continue the drug to maintain clinical benefits.
Forty-two patients with definite or classic rheumatoid arthritis entered a prospective 24-week, double-blind, parallel clinical trial, followed by an 18-month open phase. All subjects had active synovitis that was unresponsive to nonsteroidal antiinflammatory medications and conventional slow-acting antirheumatic drugs. Initial treatment with azathioprine (AZA), 100 mg/day, or methotrexate (MTX), 10 mg/week, orally, was adjusted at predefined intervals. Both treatment groups showed statistically significant improvement at week 24, compared with baseline status, in all 9 clinical outcome variables. There were no apparent statistically significant differences in these outcome variables between the 2 treatment groups. There was a trend toward a more marked and rapid improvement in the MTX-treated group. Radiologic evidence of progression of joint damage was similar in both treatment groups at 24 and 52 weeks. Four of the 42 patients (2 receiving MTX and 2 receiving AZA) discontinued the study because of side effects, and 1 MTX-treated patient withdrew because of personal reasons. Outcome measures at week 52 (open phase) were not statistically different from those at week 24. Twenty-three patients were still taking the medication at week 104. We found that AZA and MTX were similarly effective in the treatment of rheumatoid arthritis, and that this beneficial effect was maintained for up to 2 years in most patients.
Outcomes were compared between consecutive patients who had received either total lymphoid irradiation (TLI) or immunosuppressant treatment for intractable rheumatoid arthritis (RA). There were 33 TLI and 32 immunosuppressive recipients; all patients had failed standard therapy. Average followup from the start of therapy was 2.7 years for TLI and 5.9 years for immunosuppressive recipients. Final disability levels were the same in both groups; mortality was equal in both groups as well. There were more hospitalizations for infections in the TLI group and the infecting organisms tended to be staphylococcus or gram negative organisms. Apart from infections, there were more adverse effects reported in the immunosuppressive therapy group.
Immunologic functions of peripheral blood mononuclear cells were studied in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). Spontaneous IgM rheumatoid factor (IgM-RF) synthesis by unstimulated cultured blood mononuclear cells was seen in only 3 of 18 MTX-treated patients, compared with 31 of 54 RA patients who were not receiving long-acting drugs. Total IgM production by unstimulated cultured mononuclear cells, pokeweed mitogen-induced antibody synthesis, and plasma levels of IgM-RF were also lower in MTX-treated patients than in other RA patients. The numbers of circulating B cells, T4 and T8 cells, the T4:T8 cell ratio, and mitogen-induced proliferation indices were similar in MTX-treated and non-MTX-treated patients. Eleven additional patients were studied prospectively after initiation of MTX therapy. All showed significant decreases in spontaneous IgM-RF synthesis, with declining IgM-RF:IgM ratios, including all of the 9 who were studied during the first 24 hours of treatment. The results indicate that MTX has rapid effects on IgM-RF synthesis, and this action might be associated with its therapeutic efficacy in RA.
A long-term retrospective case-control study was performed comparing 119 patients with rheumatoid arthritis treated with cyclophosphamide and 119 matched control patients with rheumatoid arthritis not treated with cyclophosphamide to determine the risk of subsequent malignancy. Thirty-seven malignancies were detected in 29 cyclophosphamide-treated patients, while 16 malignancies were found in 16 control patients (p less than 0.05) during a mean follow-up period of more than 11 years. Urinary bladder cancer (six cyclophosphamide-treated patients, no control patients) and skin cancer (eight cyclophosphamide-treated patients, no control patients) were identified as differing statistically between the groups, and hematologic malignancy (five cyclophosphamide-treated patients, one control patient) showed a similar trend. Survival analysis indicated that the rate of development of malignancy in the cyclophosphamide-treated patients was significantly greater than in the control patients at six years following drug initiation, and that this increased rate persisted even at 13 years (p less than 0.01). Of the many risk factors evaluated, mean total cyclophosphamide dose and duration and tobacco use were significantly increased in patients in whom cancer subsequently developed. These long-term complications must be considered seriously when cyclophosphamide or other cytotoxic drugs are initiated for the treatment of rheumatoid arthritis.
The prevalent use of antirheumatic drugs in a cohort of 311 middle aged female patients with seropositive and seronegative rheumatoid arthritis (RA) was investigated. Seropositive patients used a greater amount and more aggressive drugs during each decade of disease duration. The overall use of drugs decreased with disease duration, except for a subgroup of seropositive patients with RA who, with increased disease duration, used more aggressive drugs.
Antimetabolites which inhibit the enzyme dihydrofolate reductase, including aminopterin and methotrexate (amethopterin) have been used in cancer and leukaemia chemotherapy since 1947. More recently, it has become a valuable alternative treatment for non-neoplastic diseases and has enjoyed its widest application in this respect as a treatment for severe psoriasis. In the subset of patients with psoriasis who develop erosive arthritis, early investigators observed improvement in both the skin and joint manifestations of psoriasis. Based largely on these observations, methotrexate has since been used to treat a variety of other arthritides and inflammatory/autoimmune diseases including Reiter's syndrome, polymyositis, polyarteritis nodosa, Wegener's granulomatosis, cyclitis, sarcoidosis and rheumatoid arthritis. In this article the authors discuss its use in rheumatoid arthritis.
We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.
Ten patients with rheumatoid arthritis were entered into a 24-week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12-week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P less than 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P less than 0.04 versus baseline in the numbers of painful/tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.
The hypothesis was tested that the shortened life expectancy of patients with rheumatoid arthritis (RA) is, partially at least, due to a familial factor which independently shortens life expectancy, whether the person has RA or not. We therefore compared the ages of death of the parents of patients with RA with the ages of the death of the parents of a control group. The parents of the patients with RA had a mean age of death of 64.76; 18.23 years versus 68.29; 18.24 years for the parents of the control group (p = 0.006). This finding is compatible with the hypothesis: whether genetic or environmental factors are involved is unknown.
Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.
Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation.
Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.
Twenty-six patients participated in a randomized, double-blind study of the efficacy of total lymphoid irradiation in the treatment of intractable rheumatoid arthritis. All 26 patients, for whom therapy with gold compounds and penicillamine had failed, would ordinarily have been considered candidates for cytotoxic or antimetabolite drug therapy. Thirteen patients randomly assigned to receive full-dose total lymphoid irradiation (2000 rad) and 11 patients assigned to receive control low-dose total lymphoid irradiation (200 rad) completed radiotherapy. Alleviation of joint disease activity was significantly greater in the high-dose group as judged by morning stiffness, joint tenderness, and functional assessment (global composite score) at 3 and 6 months after radiotherapy. The high-dose group had a marked reduction in both T-lymphocyte function and numbers, but this finding was not observed in the low-dose group. Complications seen in the high-dose but not low-dose group included transient neutropenia, thrombocytopenia, pericarditis, and pleurisy.
Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.
A prospective study in the United Kingdom of 1,634 patients without transplants treated with immunosuppressive drugs (68 percent with azathioprine, 28 percent with cyclophosphamide) found an excess of non-Hodgkin's lymphoma and squamous cell skin cancer, suggesting that the excesses (although larger) of the same malignancies found among transplant recipients are not due solely to the foreign antigens of the graft. A separate analysis of the 643 patients with rheumatoid arthritis found a 13-fold increase of non-Hodgkin's lymphoma (whether treated with azathioprine or cyclophosphamide). This increase is not significantly different from the excess in similarly treated patients with other disorders in the study. In patients with rheumatoid arthritis not receiving immunosuppressive drugs, this excess is greater than that in a Finnish population and lower than that in another United Kingdom population. The findings are consistent with other evidence that immunosuppression favors the development of non-Hodgkin's lymphoma, which includes the excess of malignancies found among transplant recipients, long-term renal dialysis patients, and patients with certain primary immunodeficiency disorders. The higher risk among transplant recipients may reflect the effects of the foreign antigens, the more intensive immunosuppressive therapy, or both of these factors. In addition, the predilection for the brain, which is a well-known feature of the lymphomas after transplantation, may also apply (to a lesser extent) to other patients after immunosuppressive treatment, judging from the increasing numbers of case reports in such patients of this exceedingly rare type of malignancy. In view of the evidence of an increase of non-Hodgkin's lymphoma in rheumatoid arthritis in the absence of immunosuppressive treatment, any additional increase is likely to be small in absolute terms. Nevertheless, it needs to be weighed against the clinical benefits.
Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p less than or equal to 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit.
Increased mortality and morbidity was seen in association with lower formal educational levels in 75 rheumatoid arthritis (RA) patients over 9 years. Nine of the 20 patients with 8 or fewer years of education had died, compared to 10 of 34 with 9-12 years of education, and only one of 21 with more than 12 years of education. Among survivors with functional capacity data available from baseline and 9 year review, declines greater than 20% were seen in 8 of 10, 13 of 21, and 9 of 19 patients in the three education categories. Overall, 79% of grade-school educated, 43% of high-school educated, and 20% of college-educated patients had either died or declined more than 50% in functional capacity. Patients of different formal educational levels were similar at baseline in age, duration of disease, measures of functional capacity, number of involved hand joints, number of severe radiographic changes, use of gold, oral corticosteroids or other therapies, and associations between formal educational level and disease course are not explained by these variables. Formal educational level appears a simple quantitative marker which identifies a surrogate or composite variable associated with increased mortality and morbidity in RA.
Uncontrolled studies have suggested that sulphasalazine may be an effective second line agent in rheumatoid arthritis. Sulphasalazine was therefore compared with placebo and intramuscular sodium aurothiomalate in 90 patients with active rheumatoid arthritis. After six months' treatment both sulphasalazine and sodium aurothiomalate had produced significant clinical and laboratory benefit, whereas placebo had produced no significant change in any variable. Thirteen patients stopped taking the placebo because of lack of effect whereas only two patients stopped taking sulphasalazine and one sodium aurothiomalate for this reason. The major toxicity encountered in the group treated with sulphasalazine was nausea or vomiting, or both; this may be related to slow acetylator phenotype. Sulphasalazine appears to be an effective second line agent, and further pharmacokinetic studies might prove useful in diminishing gastrointestinal side effects.
Solid tumors may not be as susceptible to the therapeutic effects of antibodies as are the leukemias and lymphomas, which, as single cells, are exposed to the vascular and reticuloendothelial effector systems. Ultimately, whether they are used for leukemias or solid tumors, it seems likely that antibodies will have a maximum effect when the number of target cells is low. It is for this reason that clinical trials of antibody therapy will eventually need to be done as properly randomized, controlled studies in patients who are in remission but who are at high risk for eventual relapse. The studies being conducted now are addressing the issues of toxicity and mechanism of antitumor effect. It is hoped that they will lay the foundation for the definitive studies of the future.
The effects of lymphoplasmapheresis on immunologic indices, including T cell subsets, and on clinical parameters of rheumatoid arthritis were evaluated in a controlled double-blind trial. Twenty patients were randomized to receive either 6 lymphoplasmapheresis sessions or a seemingly identical control procedure over a 3-week period. Lymphoplasmapheresis produced significant reduction in serum levels of total lymphocytes, erythrocyte sedimentation rate, C-reactive protein, and IgG. These serologic measures returned to baseline 5 weeks after lymphoplasmapheresis. No change in the imbalance of T cell subsets (increased helper/suppressor ratio) was observed. No changes in the serologic measures, except IgA, were observed in the control group. An improvement in some of the clinical parameters was observed in both the lymphoplasmapheresis and control groups. A rebound above baseline values for several parameters was observed in both the lymphoplasmapheresis and the sham apheresis groups.
A 2-year, controlled, double-blind trial of D-penicillamine and hydroxychloroquine either alone or in combination was conducted on patients with progressive rheumatoid arthritis. The group given D-penicillamine alone improved most, but a linear fall-off in efficacy occurred. Surprisingly, the group receiving combination drug therapy did not fare as well as the group receiving D-penicillamine therapy. A subset of patients receiving hydroxychloroquine therapy had prolonged benefit. Toxicity, though not uncommon, was generally not severe.
Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.