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Spondyloarthropathy treatment: progress in medical therapy
Abstract
The monitoring and treatment of the diseases belonging to the concept of spondylarthropathy are related more to their clinical presentation, for example axial versus peripheral involvement, than to the precise diagnosis, for example, ankylosing spondylitis versus psorìatic arthritis. For each clinical presentation the treatment comprises local and systemic routes of administration but also drug and non-drug therapies.
... 1) [4], et le BASFI (Bath ankylosing spondylitis disease functional index) qui compte 10 questions (tabl. 2) [5,6]. Le contrôle à long terme fait appel à la distance doigt-sol latérale et à l'ampliation thoracique. ...
... très marquée 5) Comment jugez-vous globalement l'importance de votre raideur matinale, après votre réveil? , pour prévenir la tendance à la raideur de la colonne vertébrale et la progression de l'asymétrie musculaire [6]. Une activité sportive thérapeutique adaptée à cette maladie, ou une gymnastique en groupe/ individuelle est très utile et vise à améliorer la mobilité, la force musculaire et l'endurance aérobe en général. ...
... Une activité sportive thérapeutique adaptée à cette maladie, ou une gymnastique en groupe/ individuelle est très utile et vise à améliorer la mobilité, la force musculaire et l'endurance aérobe en général. Il faut cependant éviter tous les sports imposant des secousses importantes, des efforts unilatéraux et présentant un risque exagéré de traumatisme [6]. Il n'a jamais été démontré jusqu'ici que la physiothérapie parvenait à modifier l'évolution de cette maladie, mais elle améliore très nettement la qualité de vie [6]. ...
... En fases intermedias (pacientes con limitación de la movilidad y repercusión funcional), se debe incidir en el principio de progresión del ejercicio, evitando sobrepasar el límite en el que dejará de ser beneficioso; en este sentido, se puede recomendar ayuda profesional de especialistas en ejercicio físico. En esta fase se debe recomendar una combinación de ejercicio aeróbico adaptado y uno de los programas de estiramiento-fortalecimiento que han demostrado eficacia en ensayos clínicos [21][22][23] . ...
Objective
To develop expert-based recommendations on physical activity and exercise for patients with spondyloarthritis (SpA).
Methods
Two discussion groups, one of physical therapists, rehabilitation physicians, and professionals of physical activity and sports, and another of rheumatologists interested in SpA, were held to discuss the results of a survey of rheumatologists on exercise and two focus groups with patients on barriers to exercise. Preliminary recommendations were drafted. These were submitted to the opinion of the experts in both groups according to a two round Delphi methodology.
Results
Twenty-one recommendations covering general aspects of exercise, adaptation to patient, how to deliver messages, pain management, and type of exercise and monitoring were issued. The level of agreement varied slightly between expert groups but it was high overall. Items with poor agreement were removed from the consensus.
Conclusions
We present recommendations on when and how to prescribe and monitor exercise in patients with SpA based on the opinion of experts in exercise and in SpA. We must now test whether these recommendations are useful for clinical practice and have an effect on patients with SpA seen by rheumatologists.
... En fases intermedias (pacientes con limitación de la movilidad y repercusión funcional), se debe incidir en el principio de progresión del ejercicio, evitando sobrepasar el límite en el que dejará de ser beneficioso; en este sentido, se puede recomendar ayuda profesional de especialistas en ejercicio físico. En esta fase se debe recomendar una combinación de ejercicio aeróbico adaptado y uno de los programas de estiramiento-fortalecimiento que han demostrado eficacia en ensayos clínicos [21][22][23] . ...
Objective:
To develop expert-based recommendations on physical activity and exercise for patients with spondyloarthritis (SpA).
Methods:
Two discussion groups, one of physical therapists, rehabilitation physicians, and professionals of physical activity and sports, and another of rheumatologists interested in SpA, were held to discuss the results of a survey of rheumatologists on exercise and two focus groups with patients on barriers to exercise. Preliminary recommendations were drafted. These were submitted to the opinion of the experts in both groups according to a two round Delphi methodology.
Results:
Twenty one recommendations covering general aspects of exercise, adaptation to patient, how to deliver messages, pain management, and type of exercise and monitoring were issued. The level of agreement varied slightly between expert groups but it was high overall. Items with poor agreement were removed from the consensus.
Conclusions:
We present recommendations on when and how to prescribe and monitor exercise in patients with SpA based on the opinion of experts in exercise and in SpA. We must now test whether these recommendations are useful for clinical practice and have an effect on patients with SpA seen by rheumatologists.
... Так, в терапии АС не применяются хинолиновые производные, Д-пеницилламин и соли золота из-за их неэффективности. Что же касается сульфасалазина, то он способствует снижению воспалительной активности в периферических суставах, но не в позвоночнике, и преимущественно у больных с небольшой давностью заболевания [10]. Это в равной степени относится и к метотрексату. ...
Based on the data available in the literature, the author gives information on the prevalence of ankylosing spondyloarthritis. The clinical picture and pathogenesis of this disease and the principles of its diagnosis and treatment are described. Particular emphasis is placed on the use of etoricoxib, a nonsteroidal anti-inflammatory drug, in ankylosing spondyloarthritis. The available data strongly prove that etoricoxib is an alternative in the treatment of inflammatory diseases of the joints and vertebral column, ankylosing spondyloarthritis in particular.
... However, with serial MRI to track spinal enthesitis and use of bisphosphonates to prevent glucocorticoid-induced osteoporosis, local intralesional glucocorticoids are not precluded. 147 DMARDs for enthesitis Though the efficacy of disease-modifying drugs with respect to inflammatory polyenthesopathies has not been demonstrated convincingly, 148 a few small studies suggest the efficacy of MTX in entheseal-based disease. 149 Bisphosphonates in enthesitis Pamidronate has been shown to be efficacious in treating AS. 113 However, the inflammatory indices remained high following therapy, suggesting the need for longitudinal MRI studies following the spinal changes. ...
ndian Rheumatology Association consensus statement on the diagnosis and treatment of axial spondyloarthropathies
AN Malaviya1, S Shankar2, V Arya3, V Dhir4, V Agarwal5, S Pandya6, K Shanmuganandan2, VP Chaturvedi7, CJ Das8
EPIDEMIOLOGY OF SPONDYLOARTHROPATHY
Prevalence of spondyloarthropathy in India
Indian data on the epidemiology of spondyloarthropathy (SpA) are scarce. Prevalence data from the first Indian Community Oriented Program from Control of Rheumatic Diseases (COPCORD) survey showed the rural prevalence of back pain to be 17.3%. This included both inflammatory and mechanical back aches.1 Of all the people with low backache, about 1–2% are likely to have SpA. From this rural cohort, the SpA prevalence can be estimated at about 0.17–0.34%.
Data from a large clinic in North India (with over 800 patients of rheumatic diseases on follow-up) suggests that the ratio of rheumatoid arthritis (RA) to ankylosing spondyli- tis (AS) is about 3.2:1 (unpublished data). Since the preva- lence of RA in India is about 0.7%, that of AS is likely to be about 0.2%. The prevalence of AS in a population is directly related to the frequency of HLA-B27 antigen. The frequency of HLA-B27 in the North Indian population is 6%, similar to that in Caucasians.2,3 The prevalence of AS in Caucasians is 0–1%.4
Hence, the prevalence in India is likely to be similar.
Thus, by three ways of reasoning, we can estimate the preva- lence of SpA in India to be between 0.1 and 0.2%.
Gender distribution
Males outnumber females by a ratio of 5:1 to 18.7:1.5–8 This most probably reflects: (1) Increasing awareness about AS-SpA manifestations among rheumatologists, especially that it is not uncommon among females; (2) Females may
have an atypical presentation with more extra-articular man- ifestations and root joint involvement. (3) Societal character- istics where males are able to seek medical help more easily and effectively than females. It has been suggested that peripheral arthritis is more frequently seen in females.7 In another small study that looked at 10 female and 72 male patients suffering from AS, low lumbar backac
... 9 Physiotherapy is an integral part of the management of AS and can be used in addition to, but not instead of, any anti-inflammatory medicines. 10 Although recommendations on the management of AS have been published by the Assessment of Spondyloarthritis International Society (ASAS) in collaboration with the European League Against Rheumatism (EULAR) and translated into a patient version, [11][12][13] there is a considerable need for systematic and detailed recommendations for the rehabilitation of patients with AS. ...
Physiotherapy is an integral part of the management of ankylosing spondylitis (AS) and there is a need for recommendations which focus on the rehabilitation of patients with AS. We aimed to develop recommendations for the physical therapy and rehabilitation of patients with AS based on the evidence and expertise.
The Anatolian Group for the Assessment in Rheumatic Diseases (ANGARD) is a scientific group of Turkish academicians (physiatrists and rheumatologists) who are experts in the rehabilitation of patients with AS. A systematic literature search summarizing the current available physiotherapy and rehabilitation trials in AS were presented to the experts before a special 2-day meeting. Experts attending this meeting first defined a framework based on the main principles and thereafter collectively constructed six major recommendations on physiotherapy and rehabilitation in AS. After the meeting an email survey was conducted to rate the strength of the recommendations.
Six key recommendations which cover the general principles of rehabilitation in AS in terms of early intervention, initial and follow-up assessments and monitoring, contraindications and precautions, key advice for physiotherapy methods and exercise were constructed.
These recommendations were developed using evidence-based data and expert opinion. The implementation of these recommendations should encourage a more comprehensive and methodical approach in the rehabilitation of patients with AS. Regular lifelong exercise is the mainstay of rehabilitation and there is a considerable need for well-designed studies which will enlighten the role of physical therapy in the management of AS.
... Despite its' clinical importance, treatment options for enthesitis is limited. Therapy is usually conservative, including nonsteroidal anti-inflammatory drugs, ortheses and local steroid injections (4). Disease-modifying antirheumatic drugs (DMARDs) like sulphasalazine and methotrexate are observed to have a limited role in peripheral enthesitis and are ineffective for spinal inflammation (5). ...
Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). Therapeutic effects of TNF-alpha antagonist treatments for enthesitis on imaging changes are still limited to case reports or small sample-sized trials. We aimed to investigate the potential of ultrasonography (US) to detect early changes after TNF-alpha antagonist therapy of Achilles enthesis of AS patients.
Forty-three AS patients with active disease, requiring TNF-alpha antagonist therapy, were included. Physical examination was performed to detect Achilles enthesitis and/or retrocalcaneal bursitis. US of the Achilles tendon was performed bilaterally. Grey-scale (GS) and power Doppler (PD) scores on a 0-2 semi-quantitative scale and total additive scores (TS) were calculated. Follow-up US examinations were performed 2 months after the initiation of therapy.
At baseline, 11 patients (26.2%) were symptomatic in physical examination for either Achilles enthesitis or retrocalcaneal bursitis, whereas 36 (83%) had GS US pathological findings and 10 (23.3%) had PD signal. GS score and TS decreased significantly [3.6 (3.0) vs 2.3 (2.2), P < 0.001 and 4.7 (4.9) vs 2.7 (3.3), P < 0.001, respectively], whereas the decrease in PD score was not significant after 2 months of follow-up. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ESR and CRP levels also showed significant improvements.
Subclinical Achilles enthesitis, detected only with GS US, is present in a subset of AS patients and a significant improvement can be demonstrated after 2 months of TNF-alpha antagonist therapy. In addition to standard outcome measures, US might be an additional useful tool to monitor therapy in SpA patients with Achilles enthesitis.
... Treatment of these diseases in the post-transplant period should follow standard guidelines. 17 ...
Two male patients with non-Hodgkin's lymphoma (NHL, follicular NHL, diffuse large B cell NHL, both in 2nd complete remission) and one female patient with acute myeloid leukemia in 1st complete remission developed arthralgias and enthesopathy following autologous stem cell transplantation. In 2/3 patients, sacroiliitis could be demonstrated on X-ray. In both patients, the rheumatic symptoms were classified as manifestations of a spondylarthropathy. All three patients were subsequently shown to be HLA-B27-positive. The patients were successfully treated with non-steroidal anti-inflammatory drugs. The differential diagnosis of joint pain following autologous stem cell transplantation should include HLA-B27-associated spondylarthropathies in addition to the more commonly seen bone and joint pain due to immobilization and medication.
... Drug treatment of ankylosing spondylitis (AS) is comprehensively covered in top rheumatology journals (e.g., 1,2). Exercise programs are less often discussed, although most rheumatologists consider them to be of utmost importance (3). In daily practice, however, both drug regimes and exercise programs show poor patient adherence. ...
Objectives:
The aim of the present study was to validate the Swedish version of the educational needs assessment tool (SwENAT) in undifferentiated spondyloarthritis (USpA) and use it to study the educational needs of patients with USpA.
Methods:
This was a cross-sectional study, recruiting a random sample of patients with USpA from a hospital register in Sweden. Educational needs data were collected, together with disease activity and function indices (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Bath Ankylosing Spondylitis Functional Index [BASFI]). Rasch analysis was utilized to evaluate the construct validity, internal consistency and unidimensionality of the SwENAT before studying differences in educational needs between patient subgroups (gender, age and disease severity).
Results:
Complete responses were obtained from 77 patients (48 women), with a mean age (standard deviation [SD]) of 50 (12) years, a disease duration of 16 (11) years, a BASDAI score of 4.9 (1.9) and a BASFI score of 3.1 (2.3). The SwENAT satisfied the requirements of the Rasch model (χ2 = 11.488; p = 0.119), including strict unidimensionality. Overall, the mean (SD) SwENAT score was 86 (32). Women reported higher needs than men in the domains of pain (mean [SD] 13.1 [6.8] versus 10.1 [6.0]; p = 0.05); movement (mean [SD] 13.0 [5.5] versus 9.9 [5.7]; p = 0.02) and self-help (mean [SD] 17.0 [5.8] versus 14.1 [5.0]; p = 0.03). Higher disease activity (BASDAI >4) was associated with higher educational needs (mean [SD] 92.6 [31.9] versus 73.7 [29.4]; p = 0.02).
Conclusions:
These data suggest that the SwENAT is valid in USpA. Women and patients with higher disease activity are more likely to have high levels of educational needs, so special attention and strategies to target patient education are warranted.
Traditional disease-modifying antirheumatic drugs (DMARD) are the fi rst line for the treatment of psoriatic arthritis (PsA) globally, in spite of the lack of evidence from randomized control trials. Most of the evidence comes from observational studies that will be reviewed in this chapter. Rehabilitation in rheumatology focuses on prevention of functional disorders of the musculoskeletal system, maintenance of working ability and prevention of care dependency. Rehabilitation and physical therapy is part of non-pharmacological treatment in patients with rheumatic disease. Few studies have been identifi ed in PsA, related to this issue, and are included in this review. Finally, surgery is preferably preventable, but necessary in some cases. Evidence suggests that results of orthopedic surgery in PsA are similar to those reported in other infl ammatory diseases.
Objective The aim of the present study was to evaluate whether the Dougados Functional Index (DFI) with 5-point Likert scale is sensitive enough to demonstrate the efficacy of intensive physiotherapy and exercise. Methods Eighty-one consecutive patients with spondyloarthropathy (SpA) completed self-administered questionnaires on functional analysis, the Bath Ankylosing Spondylitis Functional Index (BASH) and the DFI with 5-point Likert scale, at the beginning and end of a 3-week in-patient course based on intensive physiotherapy and exercise. The objective effect of the course was measured with 10 ranges of movement. After a 6-month follow-up the patients completed the questionnaires by mail for analysis of the lasting impact of rehabilitation on function. Results The in-patient course was highly effective: all ranges of movement and both functional indices including the DFI with 5-point Likert scale improved to a highly signficant degree. Six months later functional ability as measured by the DFI remained significantly better than at baseline before the in-patient course, but the BASH had returned to the baseline level. Conclusion The DFI with 5-point Likert scale is sensitive enough to demonstrate the effect of intensive physiotherapy and exercise.
Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects young males and is characterized by inflammatory back pain with sacroileitis and often arthritis of the peripheral joints. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. The purpose of the therapy is to reduce pain and morning stiffness, to prevent deformity, and to maintain correct posture, physical condition, psychosocial health. Nonsteroid anti-inflammatory drugs have been the gold standard in the medical therapy but their effect is regarded as symptomatic rather than curative. The effect of disease modifying antirheumatic drugs is less effective compared with other rheumatic disease such as rheumatoid arthritis. Sulphasalazine, presented recently as a second line drug, has shown some degree of efficacy, particularly in the patients with peripheral arthritis. Methotrexate was reported to be beneficial in AS in open studies, but this could not be confirmed in controlled trials. Biological agents are emerging as drugs that for the first time may provide more than just symptomatic relief to patients with AS. Anti tumour necrosis factor α (anti-TNF α) therapies, infliximab and etanercept, target the specific inflammatory processes of the disease. In placebo controlled trials, treatment with these agents resulted in rapid and significant improvement in clinic and laboratory parameters. Placebo controlled trials are still in progress to detect the long term effects and side effects of anti-TNF α therapies.
Background:
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and affects mainly the spine, but can also affect other joints. Disease progression may result in loss of mobility and function. Sulfasalazine is a disease-modifying antirheumatic drug used in the treatment of AS. However, its efficacy remains unclear. This is an update of a Cochrane review first published in 2005.
Objectives:
To evaluate the benefits and harms of sulfasalazine for the treatment of ankylosing spondylitis (AS).
Search methods:
We searched for relevant randomized and quasi-randomized trials in any language, using the following sources: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 11); MEDLINE (2003 to 28 November 2013); EMBASE (2003 to 27 November 2013); CINAHL (2003 to 28 November 2013); Ovid MEDLINE data, World Health Organization International Clinical Trials Registry Platform (28 November 2013); and the reference sections of retrieved articles.
Selection criteria:
We evaluated randomized and quasi-randomized trials examining the benefits and harms of sulfasalazine on AS.
Data collection and analysis:
Two review authors independently reviewed unblinded trial reports according to the selection criteria. Disagreements on the inclusion of the studies were resolved, when necessary, by recourse to a third review author. The same authors independently assessed the risk of bias of included trials and entered the data extracted from the included trials. We combined results using mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data.We restructured outcome measures for this update based on recommendations from the editorial group. Major outcomes included: pain, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis metrology index (BASMI), radiographic progression, total number of withdrawals due to adverse events, and serious adverse events.
Main results:
We did not add any new studies to this review following the updated search. In the original review, we included 11 studies in the analysis, involving 895 participants in total. All included studies compared sulfasalazine with placebo. We judged most of the studies as low risk of bias or unclear risk of bias in five domains (random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting, and other sources of bias). However, for incomplete outcome data, we only judged one trial at low risk of bias.None of the included trials assessed BASDAI, BASFI, BASMI or radiographic progression. Different parameters were used to assess pain. The pooled MD for back pain measured on a 0 to 100 mm visual analogue scale was -2.96 (95% confidence interval (CI) -6.33 to 0.41; absolute risk difference 3%, 95% CI 1% to 6%; 6 trials). Compared to placebo, a significantly higher rate of withdrawals due to adverse effects (RR 1.50, 95% CI 1.04 to 2.15; absolute risk difference 4%, 95% CI 0.4% to 8.8%; 11 trials) was found in the sulfasalazine group. A serious adverse reaction was reported in one patient taking sulfasalazine (Peto odds ratio 7.50, 95% CI 0.15 to 378.16).
Authors' conclusions:
There is not enough evidence to support any benefit of sulfasalazine in reducing pain, disease activity, radiographic progression, or improving physical function and spinal mobility in the treatment of AS. A statistically significant benefit in reducing the erythrocyte sedimentation rate and easing spinal stiffness was mentioned in the previous version. However, the effect size was very small and not clinically meaningful. More withdrawals because of side effects occurred with sulfasalazine. Further studies, with larger sample sizes, longer duration, and using validated outcome measures are needed to verify the uncertainty of sulfasalazine in AS.
The aim of the study was to evaluate the effectiveness of exercise therapy on physical function of patients with anklyosing spondylitis (AS) through the systemic review and meta-analysis. The 54 studies were identified from computerized search of published researches on PubMed, Embase, CINAHL, PEDro, KISS, KERIS database until February, 2008 and review of reference lists. The main search terms were the combination "ankylosing spondylitis", "exercise", "spondyloarthropathy and exercise", "ankylosing spondylitis and physical therapy". The subgroup analysis was performed by the publication year, quality score, type of disease, content of intervention, intervention provider, type of intervention, method of intervention, intervention period and the point of outcome measured. Two reviewers independently selected trials for inclusion, assessed the quality and extracted the data. The result was as follows: The 10 trials were eligible for inclusion criteria, then the systematic review and meta-analysis was assessed on effectiveness of exercise therapy. The meta-analysis of 10 studies based on the random effect model showed that the exercise therapy was beneficial in treating the diseases (effect size .55; 95% confidence interval -.3.75~.61). The findings suggest that the exercise therapy would be appropriate to manage the physical function of AS with evidence based on Meta-analysis. Therefore, the exercise therapy supervised by physical therapist should be recognized as the essential approach to manage the AS and necessarily recommended to improve physical function.
The management of patients with spondyloarthropathy is undergoing radical changes in several areas and for several reasons. The main reason seems to be improved awareness of the fairly high prevalence of this group of disorders, which is close to that of rheumatoid arthritis. Evaluation of the various treatment modalities has benefited from work by the international ASsessment in Ankylosing Spondylitis group (ASAS) group aimed at developing standardized evaluation criteria (). Controlled treatment trials have provided useful information on nonpharmacological treatments such as physical exercise programs and patient information. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of the pharmacological treatment. Recent studies have shown that NSAIDs capable of selectively inhibiting type 2 cyclooxygenase have a better gastrointestinal safety profile and are as effective in relieving clinical symptoms as conventional NSAIDs. Importantly, maintenance treatment seems effective not only on peripheral joint manifestations but also on axial manifestations that fail to respond to NSAIDs. Thalidomide and TNF antagonists are promising maintenance agents.
Das Konzept der Spondarthritiden mit Zusammenfassung verschiedener Krankheitsentitäten zu einer Gruppe erweist sich bei der Therapie als besonders sinnvoll. Die Kombination der Therapiemodalitäten orientiert sich weniger an der Diagnose als vielmehr an der klinischen Manifestation des einzelnen Patienten. Therapie der Wahl bei axialer Beteiligung sind nichtsteroidale Antirheumatika (NSAR). Bei nicht ausreichender Wirkung des NSAR kann die durch eine Sakroiliitis verursachte Symptomatik durch eine intraartikuläre Injektion von Glukokortikoiden gebessert werden. Im Fall einer therapierefraktären Erkrankung hilft bei Befall der gesamten Wirbelsäule die Glukokortikoid Pulstherapie den akuten Schub zu supprimieren. In Hinblick auf langwirksame Antirheumatika kann bisher nur Sulfasalazin als etablierte Therapie der peripheren Arthritis der Spondarthritiden und reaktiven Arthritiden betrachtet werden. Ob Sulfasalazin den Verlauf der axialen Beteiligung und der Enthesitis beeinflusst, ist zur Zeit unklar. Die Behandlung der Enthesitis besteht in der Medikation mit NSAR, physikalischer Therapie und Orthesen. Falls keine Besserung erzielt wird, sollte eine lokale Injektion mit Glukokortikoiden erfolgen. Eine niedrigdosierte Strahlentherapie ist für den Fall einer therapierefraktären Enthesitis reserviert. Wenn die genannten Therapieoptionen keinen Erfolg zeigen, wird Sulfasalazin empfohlen. Bei den reaktiven Arthritiden haben die bisherigen Antibiotikastudien keinen eindeutigen positiven Effekt auf die Erkrankung belegt. Die fehlende Effektivität der Antibiotika beruht vermutlich auf dem veränderten Metabolismus der auslösenden Erreger.
Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects mainly young men. This disease can affect axial and peripheral joints as well as specific organs, thus impairing quality of life in these patients. There are three types of treatment interventions in these patients: medical treatment, surgical treatment and physical-rehabilitation therapy. Physical-rehabilitation therapy includes distinct modalities such as hydrotherapy, electrothermotherapy, massage, rest, ergotherapy and physical therapy (PT). Among these options, PT is the most important in the treatment of AS. The main objective of PT is to preserve the normal range of movement in affected joints, depending on the stage of the disease. In this setting, many exercises for peripheral and axial joints can be performed, through rehabilitation, breathing exercises and mildly aerobic sports. Although comparison of the results of different PT interventions is difficult, a review of the literature on this subject reveals that spa-exercise therapy is better than supervised group PT, and that the latter is better than individualized PT in the home. Several extrinsic factors influence the results of the above-mentioned interventions. A clear finding is that benefits are obtained if exercise is consistently performed.
Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist. However, the spectrum of spondylarthropathy is wider than the sum of these disorders suggests. Sero-negative oligoarthritis, dactylitis or polyarthritis of the lower extremities, heel pain due to enthesitis, and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria. In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy, we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases. The diagnoses were based on the local clinical expert's opinion. The 403 patients included 168 with ankylosing spondylitis, 68 with psoriatic arthritis, 41 with reactive arthritis, 17 with inflammatory bowel disease and arthritis, and 109 with unclassified spondylarthropathy. Based on statiscal analysis and clinical reasoning, we propose the following classification criteria for spondylarthropathy inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs), together with at least 1 of the following: positive family history, psoriasis inflammatory bowel disease, urethritis, or acute diarrhea, alternating buttock pain, enthesopathy, or sacroiliitis as determined from radiography of the pelvic region. These criteria resulted in a sensitivity of 87% and a specificity of 87%. The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers. However, we regard them as preliminary until they have been further evaluated in other settings.
To estimate the prevalence of spondyloarthritis and its subtypes.
The Swedish healthcare organisation comprises a system where all inpatient and outpatient care is registered by a personal identifier. For the calendar years 2003-7, all residents aged ≥ 15 years in the southernmost county of Sweden (1.2 million inhabitants) diagnosed by a physician with spondyloarthritis (ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory arthritis associated with inflammatory bowel disease (Aa-IBD) or undifferentiated spondylarthritis (USpA)) were identified. To obtain valid point estimates of prevalence by the end of 2007, identification numbers were cross-referenced with the population register to exclude patients who had died or relocated.
The authors estimated the prevalence of spondyloarthritis (not including chronic reactive arthritis) as 0.45% (95% CI 0.44% to 0.47%). The mean (SD) age of patients with prevalent spondyloarthritis by the end of 2007 was 53 (15) years. Among the component subtypes, PsA accounted for 54% of cases, AS 21.4%, USpA 17.8% and Aa-IBD 2.3% with a prevalence of 0.25%, 0.12%, 0.10% and 0.015%, respectively. The remaining 6.4% had some form of combination of spondyloarthritis diagnoses. The prevalence of spondyloarthritis at large was about the same in men and women. However, the subtype PsA was more prevalent in women and AS was more prevalent in men.
In Sweden the prevalence of spondyloarthritis leading to a doctor consultation is not much lower than rheumatoid arthritis. PsA was the most frequent subtype followed by AS and USpA, and the two most frequent subtypes PsA and AS also display some distinct sex patterns.
To examine the efficacy of available drugs in undifferentiated spondyloarthritis (u-SpA).
Systematic review of studies retrieved from Medline (1961-July 2009), Embase (1961-July 2009), and Cochrane Library (up to July 2009). A complementary hand search was also performed. The selection criteria were as follows: (population) u-SpA patients; (intervention) nonsteroidal anti-inflammatory agents, disease-modifying antirheumatic drugs, anti-tumor necrosis factor α, anakinra, abatacept, biphosphonates, or thalidomide; (outcome) pain, function, structural damage and quality of life; (study design) randomized controlled trials (RCT), cohort studies, and case reports; (level of evidence) according to The Oxford Centre for Evidence-based Medicine (update 2009). An additional narrative review was performed to analyze the effects of drug therapies in patients with spondyloarthritis according new Assessment of Spondyloarthritis International Society criteria.
The following 7 studies were included: 2 RCT, 1 cohort study, and 4 case reports, which included 117 patients with u-SpA (mostly young men). No evidence related to the effect of nonsteroidal anti-inflammatory agents or disease-modifying antirheumatic drugs on u-SpA patients was found. Infliximab and etanercept showed some benefit regarding clinical outcomes, function, and quality of life. Two RCT reported important benefit of infliximab and adalimumab also in patients with predominantly axial spondyloarthritis. Rifampicin plus doxycycline improved some clinical outcomes but ciprofloxacin had no benefit. Anecdotal positive evidence was reported with pamidronate. No serious adverse events were reported in the retrieved studies.
Low-quality evidence suggests a benefit of tumor necrosis factor α blockers in u-SpA and good-quality evidence in predominantly axial spondyloarthritis. The use of antibiotics remains controversial. High-quality trials are needed to definitively assess the effect of available drugs in these patients.
The objective of the study was to investigate the response rate to non-steroidal anti-inflammatory drugs (NSAIDs) and the clinical parameters that might predict this response in patients with active ankylosing spondylitis. This is a prospective, observational, 3-month study that was conducted in a single center. Ninety-five consecutive patients with active ankylosing spondylitis were included in the study. Full dose NSAIDs (indometacin 150 mg daily or acemetacin [corrected] 180 mg daily) were given to patients. Relevant clinical data of all patients' were recorded at the beginning and on three consecutive monthly visits. At the end of the study period, patients who respond to NSAIDs were determined. Demographic, clinical, and laboratory parameters that might influence the response to the NSAIDs were investigated. The response rate to the full-dose NSAIDs according to the ASAS20 in patients with active ankylosing spondylitis was found as 29.5%. Similarly, 20.0% of the patients were responders according to the ASAS40 criteria, whereas 5.6% of the patients responded according to the 5-out-of-6 criteria at week 12. Patients who responded to the treatment were found to be younger at the study entry (P = 0.001) and had shorter disease duration (P < 0.001). Due to the markedly lower rate of response to the NSAIDs in patients with active ankylosing spondylitis, early identification of those patients who does not respond to NSAIDs and subsequent decision regarding the institution of second-line treatments (anti-TNF) may be of great value in the prevention of irreversible changes that might develop in most of the patients.
by Moll et al. (2) the school of 'lumpers', who preferred Infection of the urogenital or gastrointestinal tract to group the so-called 'variants of rheumatoid arthritis' Alteration of the skin (psoriasiform skin or nail lesion, with rheumatoid arthritis itself, were overcome by the erythema nodosum) school of 'splitters', prompted by the idea that these Buccal ulceration of the mouth, small or large intestine and seronegative arthritides were, in fact, entirely separate urogenital tract Thrombophlebitis entities. This change was mirrored by the Nomenclature Pyoderma gangraenosum and Classification of the Rheumatic Diseases proposed Familial aggregation by the American Rheumatism Association in 1963 (1). Association with HLA-B27 Rheumatoid arthritis, juvenile Still's disease, ankylosing spondylitis, psoriatic arthritis, and Reiter's syndrome 1. The term seronegative arthritis still survives and is were then classified under separate headings with the not completely out of use, which may be illustrated common denominator 'polyarthritis of unknown origin'. by the fact that the Editor of this journal initially
The management of spondyloarthropathy (SpA) is based more on clinical presentation (axial vs peripheral involvement) than on actual disease diagnosis. Treatment is aimed at controlling inflammation, ankylosis, and abnormal posture. Nonsteroidal antiinflammatory agents are the cornerstone of treatment for patients with axial involvement. If these do not work, disease controlling antirheumatic therapy is usually prescribed. Several drugs, particularly sulfasalazine, produce clinically significant improvement in patients with articular peripheral involvement. In contrast, the therapeutic options for patients with refractory axial involvement are very limited. For this group, "potential" (pamidronate, thalidomide) or "specific" (infliximab) tumor necrosis factor blockers are of potential interest and deserve further evaluation. Therapeutic efficacy is monitored chiefly according to clinical variables, although biochemical markers such as C reactive protein are also helpful.
The management of patients with spondyloarthropathy is undergoing radical changes in several areas and for several reasons. The main reason seems to be improved awareness of the fairly high prevalence of this group of disorders, which is close to that of rheumatoid arthritis. Evaluation of the various treatment modalities has benefited from work by the international Assessment in Ankylosing Spondylitis group (ASAS) group aimed at developing standardized evaluation criteria. Controlled treatment trials have provided useful information on non-pharmacological treatments such as physical exercise programs and patient information. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of the pharmacological treatment. Recent studies have shown that NSAIDs capable of selectively inhibiting type 2 cyclooxygenase have a better gastrointestinal safety profile and are as effective in relieving clinical symptoms as conventional NSAIDs. Importantly, maintenance treatment seems effective not only on peripheral joint manifestations but also on axial manifestations that fail to respond to NSAIDs. Thalidomide and TNF antagonists are promising maintenance agents.
There is currently no universal consensus on nomenclature for spondyloarthropathy (SpA), or on activity and severity criteria for ankylosing spondylitis (AS).
Points of agreement and majority opinions among 28 international experts in the field were identified by questionnaire. Agreement was defined as >80% concurrence, clear majority as >60% concurrence, and a majority or trend as >50% concurrence.
Respondents agreed on the need for one term that reflects the inflammatory nature of the disease, but no agreement was reached on a specific term. Agreement included subdivision of patients with SpA into AS, psoriatic arthritis, inflammatory bowel disease associated arthritis, and undifferentiated spondyloarthritis/spondyloarthropathy. A majority of experts defined active disease as fulfilling classification criteria for AS and/or a SpA, and disease activity measured by a Bath AS Disease Activity Index (BASDAI) score >4 determined by two patient visits during a two month period, but no maximum radiographic score. The majority of participants considered failure of treatment response to non-steroidal anti-inflammatory drugs (NSAIDs) alone to be a prerequisite for active/severe AS, and 15/28 (54%) thought that NSAID treatment failure should be defined as lack of response to two or more NSAIDs.
Respondents agreed that a two to five year study is the ethical method to demonstrate effects of anti-tumour necrosis factor alpha (TNFalpha) therapy on radiographic progression of AS, and that inclusion criteria should include a certain level of disease activity (measured by BASDAI) and failure of certain treatments. After the efficacy of anti-TNFalpha therapy in AS and psoriatic arthritis is proved, respondents agreed that more studies will be needed to show efficacy for other SpA subsets.
Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. Currently available conventional treatments are palliative at best, and often fail to control symptoms in the long term. Current drug treatment may perhaps induce a spurious state of "disease remission," which is merely a low level of disease activity. Non-steroidal anti-inflammatory drugs are first line treatment, but over time, the disease often becomes refractory to these agents. Disease modifying antirheumatic drugs are second line treatment and may offer some clinical benefit. However, conclusive evidence of the efficacy of these drugs from large placebo controlled trials is lacking. Additionally, these drugs can cause treatment-limiting adverse effects. Intra-articular corticosteroid injection guided by arthrography, computed tomography, or magnetic resonance imaging is an effective means of reducing inflammatory back pain, but controlled studies are lacking. A controlled study has confirmed moderate but significant efficacy of intravenous bisphosphonate (pamidronate) treatment in patients with AS; further evaluation of bisphosphonate treatment is warranted. Physical therapy and exercise are necessary adjuncts to pharmacotherapy; however, the paucity of controlled data makes it difficult to identify the best way to administer these interventions. Surgical intervention may be required to support severe structural damage. Thus, for patients with AS, the future of successful treatment lies in the development of pharmacological agents capable of both altering the disease course through intervention at sites of disease pathogenesis, and controlling symptoms.
Ankylosing spondylitis (AS) is a complex, potentially debilitating disease that is insidious in onset, progressing to radiological sacroiliitis over several years. Patients with symptomatic AS lose productivity owing to work disability and unemployment, have a substantial use of healthcare resources, and reduced quality of life. The pathogenesis of AS is poorly understood. However, immune mediated mechanisms involving human leucocyte antigen (HLA)-B27, inflammatory cellular infiltrates, cytokines (for example, tumour necrosis factor alpha and interleukin 10), and genetic and environmental factors are thought to have key roles. The detection of sacroiliitis by radiography, magnetic resonance imaging, or computed tomography in the presence of clinical manifestations is diagnostic for AS, although the presence of inflammatory back pain plus at least two other typical features of spondyloarthropathy (for example, enthesitis and uveitis) is highly predictive of early AS. Non-steroidal anti-inflammatory drugs (NSAIDs) effectively relieve inflammatory symptoms and are presently first line drug treatment. However, NSAID treatment has only a symptomatic effect and probably does not alter the disease course. For symptoms refractory to NSAIDs, second line treatments, including corticosteroids and various disease modifying antirheumatic drugs, are employed but are of limited benefit. Emerging biological therapies target the inflammatory processes underlying AS, and thus, may favourably alter the disease process, in addition to providing symptom relief.
1 The course of AS is highly variable and can be characterised by spontaneous remissions and exacerbation, particularly in early disease. The disease activity, however, generally persists for many decades, rarely entering a long term remission.The disease in some patients may be relatively mild or stay limited to the sacroiliac joints and the lumbar spine. Many patients may not seek medical help, which com- bined with the insidious nature of AS, may preclude an early diagnosis. There is currently no cure for AS, nor is there any medical intervention which can prevent or retard its progres- sion.
The conceptual understanding of SpA and the ability to image sites of skeletal inflammation accurately and confirm that enthesitis is the primary lesion has occurred around the same time as the greatest therapeutic advances in AS and SpA with the advent of potent anti-TNF therapies for enthesitis. These therapies have transformed the understanding of enthesitis and revolutionized therapy of what was often an intractable problem. Now that clinicians better understand enthesitis-related disease mechanisms and have the ability to image them in early disease and monitor them, there is an urgent need to assess optimal conventional drug therapy in these conditions.
Chlamydia-induced arthritis is the most frequent form of reactive arthritis in Western countries. This article gives an overview of the recent findings with respect to diagnosis, pathogenesis, and therapy of the disease.
Recent advances in the modification and standardization of polymerase chain reaction techniques give promise to identify Chlamydia more frequently from joint samples. Based on the sequenced chlamydial genome, considerable progress has been achieved in the understanding of the Chlamydia-host cell interaction, indicating that persistence is an alternate state of the bacteria used by Chlamydia to escape the immune system of the host rather than a general stress response. Furthermore, Chlamydia has the ability to reprogram the host cell by chlamydial effector proteins, which are transported from the inclusion into the host cell cytoplasm. The role of HLA-B27 is discussed in view of the pathogenesis of the disease. HLA-B27 should be considered a risk factor for chronic and/or axial disease rather than a true susceptibility factor for the development of Chlamydia-induced arthritis. No progress has been made in terms of causative therapy aiming at eradication of the bacteria. Tumor necrosis factor-alpha blocking agents may represent a new option in cases that are refractory to therapy.
Molecular biology not only has improved the ability to detect Chlamydia in the joint for diagnostic purposes but also has extended the current understanding of the pathogenesis of the disease. In contrast to this progress, causative therapy of Chlamydia-induced arthritis is still an unfulfilled need.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. To date, treatment of AS has been limited to the alleviation of symptoms, mainly using non-steroidal anti-inflammatory drugs (NSAIDs). For patients refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Methotrexate (MTX) is currently one of the most widely used DMARDs and its efficacy in rheumatoid arthritis (RA) has been confirmed (Suarez-Almazor 2003). There is uncertainty whether MTX works in the treatment of AS.
To evaluate the efficacy and toxicity of methotrexate in the treatment of ankylosing spondylitis.
Relevant randomised and quasi-randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles.
We evaluated randomised and quasi-randomised trials examining the efficacy of methotrexate on AS.
Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan's double entry facility. In the absence of significant heterogeneity, results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data.
Two trials met the inclusion criteria. Altan 2001compared naproxen plus MTX (7.5 mg/week orally) with naproxen alone and Roychowdhury 2002 compared MTX (10 mg/week orally) with placebo. The duration of the trials were 12 months and 24 weeks, respectively. They assessed different outcomes except for C-reactive protein (CRP). The included trials treated a total of 81 patients and assessed more than 10 outcomes relevant to the review, covering function, pain, peripheral arthritis/enthesitis, morning stiffness, patient and physician global assessment, CRP and erythrocyte sedimentation rate (ESR). No significant difference between intervention groups was found favouring MTX over no MTX. No serious side effect was reported in either trial.
There was no statistically significant benefit of MTX in the examined outcomes for AS patients. High quality, larger sample and longer period of randomized controlled trials (possibly with higher dosage of MTX) are needed to verify the uncertainty about the efficacy and toxicity of MTX for the treatment of AS.
To examine the subjective health in patients with ankylosing spondylitis (AS) compared with the general population, and to explore the associations between health status and age, sex of the patients, and educational level in AS.
Health status was assessed with a generic instrument (SF-36) in 314 patients with AS and in 2323 people from the general population. Subgroup analyses were performed according to age, sex, and educational level. Standard difference scores (s-scores) were calculated to ensure the clinical meaningfulness of the norm based comparisons.
Both men and women with AS reported significantly impaired health on all scales of the SF-36. Women reported significantly worse health on physical health domains. However, when calculating differences from the general population, numerically larger s-scores were found for men (except for physical role and vitality). The relative impact of AS seems to diminish with increasing age. In AS, better health was significantly associated with higher education across all scales. Deviations from the general population on the non-physical health aspects were especially pronounced in patients with low education.
All key dimensions of health are affected by AS. The physical aspects seem to be most severely affected, but in the less educated group of patients, the disease impact on the mental health aspects was also considerable. Evaluation and management planning should take the complexity of AS into consideration. The focus on physical function should be maintained, and additional attention should be paid to the mental and social consequences of AS.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and belongs to a group of diseases known as spondyloarthropathies (SpA), which includes reactive arthritis, arthritis/spondylitis in inflammatory bowel disease, psoriatic arthritis/spondylitis and undifferentiated SpA. Non-steroidal anti-inflammatory drugs (NSAIDs) have been the main treatment for AS. For those refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Sulfasalazine (SSZ) is the best studied DMARD in AS, but its efficacy remains unclear.
To evaluate the efficacy and toxicity of sulfasalazine for the treatment of ankylosing spondylitis.
Relevant randomised and quasi-randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles.
We evaluated randomised and quasi-randomised trials examining the efficacy of sulfasalazine on ankylosing spondylitis.
Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan double entry facility. Results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data.
Twelve studies met the inclusion criteria but only eleven were included in the data analysis. The pooled analysis showed that the difference between intervention groups was significant only in erythrocyte sedimentation rate (ESR) (WMD -4.79, 95% CI -8.80 to -0.78) mm/h) and morning stiffness VAS-100 mm (visual analogue scale 100 mm, where 0 = no stiffness and 100 = severe) (WMD -13.89, 95% CI -22.54 to -5.24), favouring SSZ over placebo. The trial with the largest sample (Clegg 1996) and that with the longest treatment duration (Kirwan 1993) had similar results. Both trials found that SSZ showed evidence of benefit in the occurrence of peripheral joint symptoms and peripheral responses in patients with peripheral arthritis. Nissila 1988 is the only trial in which SSZ showed benefit in primary outcome analyses, including back pain, chest expansion, occiput-to-wall test and patient's general well being. Compared with other trials, the patients in this trial had the shortest disease duration and the highest level of baseline ESR and contained the greatest proportion of patients with peripheral arthritis. Significantly more withdrawals for side effects (RR 1.50, 95% CI 1.04 to 2.15, NNH 23, 95% CI 10 to 288) and for any reason (RR 1.33, 95% CI 1.03 to 1.73, NNH 17, 95% CI 8 to 180) were found in SSZ compared with placebo group although severe side effects were rare (1 of the 469 patients taking SSZ).
Across all AS patients, SSZ demonstrated some benefit in reducing ESR and easing morning stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, patient and physician global assessment. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ.
Efficacy of a second magnetic resonance (MR) imaging guided corticosteroid injection of inflamed sacroiliac joints (SIJ) in patients with spondylarthropathy. Thirty-one patients received 50 injections in an outpatient basis. Fifteen of 31 patients who relapsed or were non-responders received a second injection. All had MR guided injection of 40 mg triamcinolone acetonide into SIJ using an open 0.2 Tesla unit. Twenty of 31 patients after the first injection, and 9 of 15 patients after the second injection reported subjective improvement, which lasted for a mean of 8.7+/-10.9 and 16.1+/-15.8 months for each group. Subchondral bone marrow edema resolved in 15 of 20 patients who reported subjective improvement, after the first injection. No complications occurred. MR guided steroid injection of SIJ is effective and safe. Since there is no exposure to radiation it could be performed many times. Repeated injections seem to be beneficial for primary non-responders and patients who relapsed.
The objective of the study is to describe the use, clinical efficacy, and toxicity of nonsteroidal anti-inflammatory drug (NSAID) therapy in patients with ankylosing spondylitis (AS). A cross-sectional population study of 1,080 AS patients was carried out by a written questionnaire in the year 2000. Seventy-eight percent of AS patients had regularly taken NSAIDs for their disease 12 months prior to the study. Most AS patients commonly used diclofenac, naproxen and indomethacin. AS patients were generally rather satisfied with the efficacy of their therapy where 19.1% reported complete pain control, 26.8% reported pain reduction to one quarter, and a further 34.4% reported pain reduction to one half. However, over 20% of patients taking NSAIDs still reported insufficient pain control and more than 40% changed the NSAID due to lack of efficacy. One quarter of AS patients reported severe side effects from their treatment, most commonly abdominal pain, headache and dizziness, and nausea. There was no effect on age or duration of disease on the occurrence of NSAID-related side effects. Medications were commonly ceased or changed due to inefficacy or side effects. The percentage of AS patients reporting changing their NSAID due to side effects ranged from 10.5% for celecoxib to 31.4% for indomethacin. We conclude that NSAIDs are effective in the management of inflammatory symptoms of many, but not all, patients with AS. There is a significant side effect profile, which frequently results in medication change or cessation. Anti-tumor necrosis factor therapy may reduce the need for intensive long-term NSAID therapy in AS.
Ankylosing spondylitis (AS) is a chronic systemic rheumatic disease that primarily affects the sacroiliac joints and spine. Even with the development of tumor necrosis factor-alpha inhibitors, which have revolutionized the treatment of this disease, the combination of nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and a life-long exercise program still form the first step in its management. Multiple clinical trials have addressed the efficacy and safety of both nonselective and selective NSAIDs. Gastrointestinal toxicity remains their major side effect, with increased concern about the potential of cardiovascular toxicity, especially with the selective cyclooxygenase-2 inhibitors. A specific set of recommendations has been proposed for the management of AS.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterised by sacroiliitis and spondylitis. Generally, treatment is limited to the alleviation of symptoms using non-steroidal anti-inflammatory drugs (NSAIDs). Recently, disease-modifying antirheumatic drugs (DMARDs) have been used for patients for whom NSAIDs do not work. Methotrexate (MTX), a widely used DMARD, is effective for rheumatoid arthritis (RA), and so might work for AS too.
To evaluate the efficacy and toxicity of MTX for treating AS.
We conducted searches in any language in: CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 20, 2005); EMBASE (1980 to November 20, 2005); CINAHL (1982 to November 20, 2005), and the reference sections of retrieved articles.
Randomised and quasi-randomised trials examining the efficacy of MTX versus placebo, other medication, or no medication, for AS.
Two reviewers independently assessed unblinded trial reports for inclusion, assessed methodological quality and entered trial data into RevMan 4.2 using the double-entry facility. Disagreements were resolved by a third reviewer. In the absence of significant heterogeneity, results for continuous data were combined using weighted mean difference or standardised mean difference. Relative risk was used for dichotomous data.
Three trials, involving 116 patients, were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. Only the response rate in one trial showed a statistically significant benefit of 36% in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX is questionable. No serious side effects were reported in these trials.
There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality randomised controlled trials of longer durations and with larger sample sizes are needed to clarify the effect(s) of MTX on AS.
Ankylosing spondylitis (AS) is a chronic inflammatory disease requiring regular medical care and monitoring to alleviate symptoms, maintain function, identify disease progression and initiate appropriate, timely therapies. Monitoring of the AS patient in clinical daily practice should not only include general history taking and physical examination, but also incorporate specific concepts, pertaining to the disease, which will aid in the detection of disease progression, the requirement of therapeutic intervention and the response to therapy. The Assessments in AS (ASAS) international working group has defined a core set of disease concepts that should be a part of everyday clinical record-keeping in AS, and has identified and validated measurement instruments corresponding to these health concepts, which can easily be incorporated into clinical practice. The group has also developed recommendations for management and a consensus statement for the use of biological therapies in AS, which includes recommendations for the monitoring of AS patients receiving these therapies. This chapter reviews the recommendations for monitoring AS patients in daily clinical practice, with particular regard to those receiving biological treatments.
We investigated survival of a group of 151 Canadian war veterans with ankylosing spondylitis who were entered into a prospective study in 1947–1949. With 94% successful followup, total survival was 60.9%, significantly less than expected. However, a subgroup who had not been treated with radiotherapy had a survival not significantly different from the general population. Causes of death in both irradiated and nonirradiated subgroups were determined.
Objective:
To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy.
Methods:
Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments.
Results:
While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints.
Conclusion:
SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.
Objective. To assess the effects of antibiotic treatment of urethritis or cervicitis on the incidence of recurrences of articular symptoms in Reiter's syndrome patients.
Methods. Retrospective evaluation of the medical charts of 109 patients living in Greenland.
Results. Thirty-seven percent of the episodes of genitourinary tract inflammation that were not treated or were treated with penicillin were followed by arthritis, compared with 10% of those treated with tetracycline or erythromycin.
Conclusion. Antibiotics active against Chlamydia trachomatis reduced the risk of postvenereal arthritis in the population studied.
Objective. To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondyl-arthropathy.
Methods. We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population.
Results. Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment.
Conclusion. The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.
Eighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (≤3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS.
The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist. However, the spectrum of spondylarthropathy is wider than the sum of these disorders suggests. Sero-negative oligoarthritis, dactylitis or polyarthritis of the lower extremities, heel pain due to enthesitis, and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria. In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy, we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases. The diagnoses were based on the local clinical expert's opinion. The 403 patients included 168 with ankylosing spondylitis, 68 with psoriatic arthritis, 41 with reactive arthritis, 17 with inflammatory bowel disease and arthritis, and 109 with unclassified spondylarthropathy. Based on statiscal analysis and clinical reasoning, we propose the following classification criteria for spondylarthropathy inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs), together with at least 1 of the following: positive family history, psoriasis inflammatory bowel disease, urethritis, or acute diarrhea, alternating buttock pain, enthesopathy, or sacroiliitis as determined from radiography of the pelvic region. These criteria resulted in a sensitivity of 87% and a specificity of 87%. The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers. However, we regard them as preliminary until they have been further evaluated in other settings.
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In the medical application of radium-224 for injection the radio-nuclidic purity of the product is a question of considerable importance. The contamination caused by the long-lived nuclides 226Ra, 228Ra, 227Ac, and 228Th must be limited to minimize their incorporation and the long-term skeletal dose received by the patients. The purification of the source material 228Th for manufacturing 224Ra and the extraction of 224Ra from 228Th are described. The actual trace amounts of the long-lived radioactive impurities in the injection solutions are compared with the maximum permissible body burdens recommended by ICRP. Buchler and Co. (since 1971 Amersham Buchler) is, as far as we know, the only producer of 224Ra for injection. We recommend a total activity of 10 x 28 [mu]Ci of 224Ra for the therapy of ankylosing spondylitis. Taking this total activity, the injection of any long-lived radionuclide from 1967 through 1973 was less than 0.2% of its maximum permissible body burden. (C)1978Health Physics Society
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Selected References
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Dixon AJ, Davies J, Dormandy TL, Hamilton EB, Holt PJ, Mason RM, Thompson M, Weber JC, Zutshi DW. Synthetic D(-)penicillamine in rheumatoid arthritis. Double-blind controlled study of a high and low dosage regimen. Ann Rheum Dis. 1975 Oct;34(5):416–421. [PMC free article] [PubMed]
The efficacy of intensive inpatient physiotherapy was retrospectively analysed in 505 adult patients with ankylosing spondylitis (AS). Eight different measures of thoracic and spinal mobility were collected from the patients' medical records. Recovery in terms of the following measures was 7 to 37% when results after rehabilitation were compared to those taken before: thoracolumbar flexibility (TLF) 15%, the Schober test 12.4%, occiput to wall distance (OWD) 30.8%, cervical rotation 22.6%, chin to chest distance (CCD) 21.7%, finger to floor distance (FFD) 36.6%, chest expansion (CE) 31.3%, vital capacity (VC) 7.4%. Changes in all measures were statistically significant (p less than 0.001). OWD, CE and FFD showed greatest improvement. The average increase in CE was about 1 cm in both sexes and the average increase in VC200 ml in men and 270 ml in women, which indicates improvement in ventilatory capacity. Mobility in the majority of patients improved, though in 2 to 8% range of motion (ROM) deteriorated during the course.
The aim of this double-blind study was to compare the effect of high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy administered intravenously once daily for three consecutive days, in active ankylosing spondylitis. Seventeen patients with active ankylosing spondylitis were randomly allocated to high-dose (8 patients) or low-dose (9 patients) regimen. Although there was no placebo group in this study, it is our impression that in patients with active ankylosing spondylitis, both high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy given on three consecutive days, is effective as regards pain relief and improvement in spinal mobility. There were no statistically significant differences between the two groups, though there was a trend towards the high dose yielding a greater and longer lasting improvement. No serious adverse reactions were observed.
We conducted a double-blind, placebo-controlled, randomized study of 3-month treatment with lymecycline, a form of tetracycline, in reactive arthritis (ReA). Lymecycline therapy significantly decreased the duration of the illness in patients with Chlamydia trachomatis-triggered ReA, but not in other ReA patients. In 2 ReA patients, C trachomatis was found in the throat, an uncommon locale for this organism. Our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat Chlamydia arthritis patients with a prolonged course of tetracycline.
Methods for scoring the severity of radiological change in patients with ankylosing spondylitis using plain X-rays of the sacroiliac (SI) joints and lumbar spine and computerized tomographic (CT) scans of the SI joints were evaluated in a cohort of 70 patients. Analysis of reproducibility was by the kappa statistic. Significant change over 12 months in a subgroup of patients was demonstrated by these scores. Ankylosis correlates negatively with erosions and sclerosis and the change in SI joint ankylosis correlates negatively with change in SI joint erosions as seen on CT scan. The clinical and laboratory correlates of these findings were examined. Pain, stiffness and sleep disturbance correlated positively with increasing SI joint sclerosis on CT scanning (r = 0.45; P less than 0.05) but negatively with ankylosis (r = -0.43; P less than 0.05). Orosomucoid levels predicted an increase in the radiological lumbar spine score. No other clinical or laboratory variable predicted radiological change.
Two sets of criteria have been proposed to discriminate spondylarthropathies (SA) from other rheumatic diseases. To evaluate their performance, we conducted a cross-sectional study in the patients observed during one week in 28 French Departments of Rheumatology by 91 staff-teaching physicians. The physicians had to apply these criteria to all their patients and had to classify them as definite SA, definite other rheumatic disease or possible SA. The analysis performed on the 2,088 patients with a definite diagnosis (124 SA and 1,964 controls) showed the following results: (table; see text) Of the 140 patients with possible SA, 37 fulfilled both sets of criteria, 22 the ESSG criteria alone and 12 the Amor criteria alone. These data suggest that a) the overall performance of these two sets of criteria is similar; b) this performance is better in the group of patients with a definite diagnosis; c) the patients without a definite diagnosis require a longer follow-up to assess the clinical relevance of these two sets of criteria.
Fifty-three patients with ankylosing spondylitis (AS) were randomly allocated; 26 experimental patients received physiotherapy and disease education, 27 control patients received neither. The primary treatment outcome was change in spinal mobility measured at 4 months by fingertip-to-floor distance. Experimental patients had more improvement in fingertip-to-floor distance (p2 less than 0.004) and in function (p2 less than 0.001) than control patients. Physiotherapy with disease education is effective in the treatment of patients with AS.
Thirty three patients with definite ankylosing spondylitis (AS) were examined to establish the relation between restriction of chest expansion, limitation of lung function, and working capacity or exercise tolerance. As in previous studies there was a significant association between chest expansion and lung vital capacity. There was also a significant association between vital capacity and exercise tolerance as measured by a subject's maximum oxygen capacity (VO2max). Both vital capacity and VO2max were expressed as a percentage of predicted normal values using patients' height before disease. In this study chest expansion did not have a significant effect on exercise tolerance. The results suggested that patients who took a modest amount of exercise regularly could maintain a satisfactory work capacity despite very restricted spinal and chest wall mobility. It is recommended that greater emphasis should be given to encouraging patients with AS to maintain cardiorespiratory fitness as well as spinal mobility.
In recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis. Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking. In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis. Evaluation after three months' treatment showed reduction of inflammatory activity and improvement of clinical variables. The side effects were mild. The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis.
Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis.
We describe an index of functional impairment and a system of scoring joint tenderness for use in the assessment of ankylosing spondylitis. The functional index consists of 20 questions and the articular index is based on the scoring of a total of 10 joint responses after movement or firm digital pressure. These indices are simple to establish and not time consuming. They have a high degree of intra- and interobserver reproducibility. The indices showed changes in short term clinical trials of antiinflammatory drugs; these changes were highly correlated with the patient's overall assessment of his own clinical condition.
The incidence of lens opacifications that impaired vision (cataract) was analyzed among 831 patients who were injected with known dosages of 224Ra in Germany shortly after World War II. The dependence of the incidence on dosage, i.e., injected activity per unit body weight, and on time after treatment was determined. The observations are equally consistent with proportionality of the incidence of cataract to the square of dosage or with a linear dependence beyond a threshold of 0.5 MBq/kg. The possibility of a linear dependence without threshold was strongly rejected (P less than 0.001). The analysis of temporal dependences yielded a component that was correlated with the injected amount of 224Ra and a component that was uncorrelated. The former was inferred by a maximum likelihood analysis to increase approximately as the square of the time after treatment. The component unrelated to the treatment was found to increase steeply with age and to become dominant within the collective of patients between age 50 and 60. The relative magnitudes of the two components were such that a fraction of 55 to 60% of the total of 58 cataracts had to be ascribed to the dose-related incidence. Impaired vision due to cataract was diagnosed before age 54 in 25 cases. In terms of injected activity per unit body weight no dependence of the sensitivity on age was found; specifically there was no indication of a faster occurrence of the treatment-related cataracts in patients treated at older ages.
Thirty two patients with ankylosing spondylitis were investigated with a set of pulmonary function tests and the results compared with those for a control population. The patients had no complaints about lung symptoms and their chest radiographs were normal. The main pathological findings were reduced lung volumes, a raised closing volume/vital capacity ratio, and a decreased volumic airway conductance. The lung volume reduction correlated with disease duration, thoracic mobility, and degree of acute phase reaction. The stiff spondylitic thorax probably makes the main contribution to the impairment of lung function in these patients, but the findings in this study also suggest an involvement of the small airways. This type of pulmonary function testing seems valuable even in patients with ankylosing spondylitis without lung symptoms and it might be used as a tool in the staging of the disease, to evaluate treatment and to differentiate from fibrosis.
A controlled study of 39 consecutively-admitted patients with ankylosing spondylitis was conducted to assess the effects of daily passive stretching of the hip joints during a 3-week in-patient physiotherapy course. Measurements were performed by an independent assessor on admission, at discharge and six months after discharge.
Results showed that passive stretching resulted in a significant increase in the range of all movements of the hip joints except flexion during the physiotherapy course.
Follow-up at 6 months in seven patients suggested that this increase in range of movement could be maintained by patients who had been performing the stretching exercises regularly.
We suggest that the inclusion of passive stretching of the hip joint in the treatment of patients with ankylosing spondylitis will increase the range of movement and thus improve function and influence posture.
A double blind placebo controlled trial was carried out over a 6-month period on 17 patients with ankylosing spondylitis (AS) to assess the effect of the second line antirheumatic drug, D-penicillamine. The patients included 13 with peripheral joint involvement. No significant improvement over placebo was detected in a variety of clinical and laboratory indices in the patients receiving active treatment. This controlled trial would not support a use for penicillamine in AS.
A double-blind cross-over study in 35 patients with ankylosing spondylitis was carried out comparing flurbiprofen (150 mg daily)-a new non-steroidal anti-inflammatory agent-with phenylbutazone (300 mg daily) over a four-week period. Flurbiprofen was well tolerated and shown to have therapeutic efficacy approaching that of phenylbutazone. The results suggest that flurbiprofen may prove a valuable alternative in the treatment of ankylosing spondylitis, and longterm efficacy and tolerance studies are clearly indicated.
The Dunham spondylometer is described and a range of normal values for its use is established. A short retrospective study
of patients with ankylosing spondylitis whose progress has been monitored using this instrument is reported. The range of
extension in spondylitics was found to be consistently below the value obtained for the normal population. Total range of
spinal mobility in the spondylitic group decreased slowly over a period of fourteen years. The need for prospective studies
of spinal mobility in ankylosing spondylitis is emphasized.
The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
We investigated survival of a group of 151 Canadian war veterans with ankylosing spondylitis who were entered into a prospective study in 1947-1949. With 94% successful followup, total survival was 60.9%, significantly less than expected. However, a subgroup who had not been treated with radiotherapy had a survival not significantly different from the general population. Causes of death in both irradiated and nonirradiated subgroups were determined.
Long-term effects of three or four-week inpatient physiotherapy and exercise courses were studied in 141 adult patients with ankylosing spondylitis (AS). Eight cervical and thoracolumbar range of motion (ROM) measurements and straight leg raise test, vital capacity (VC) and fitness index were measured at the beginning and end of an intensive course and 15 months later. All nine mobility measurements, vital capacity and fitness index were significantly improved after the course. Fifteen months later only chest expansion and vital capacity had significantly deteriorated from the baseline, while CR, FFD and fitness index were still significantly better. Disease duration did not influence treatment results. We conclude that it is possible by means of intensive rehabilitation courses to prevent for more than one year deterioration of spinal function and fitness in AS patients irrespective of disease duration.
The purpose of this study was to evaluate how improvements in global health in patients with ankylosing spondylitis (AS), who had received group physical therapy, were associated with changes in physical functioning and other outcome measures. Sixty-seven AS patients from 2 outpatient departments (modified New York criteria) received group physical therapy weekly. After 9 months we studied the following variables to explain changes in global health: disease duration, spinal mobility, fitness, functional status (SIP, HAQ and Functional Index), pain, stiffness, and articular and enthesis indices. Change scores were calculated as baseline values minus scores at 9-month follow-up. Personality traits (neuroticism, social inadequacy, self-esteem and health locus of control) and loneliness were also included as possibly explanatory variables. Patient's assessment of change in global health after 9 months of group physical therapy was self-reported on a 10 cm visual analogue scale (-5 = maximum worsening, 0 = no change, +5 = maximum improvement). Correlations were calculated between change in global health and all candidate explanatory variables. In this pre/post test design multiple and stepwise regression analyses were performed to study the relations between changes in global health and all explanatory variables. Pearson correlation coefficients between improved global health and the explanatory variables were significant for lower self-esteem (0.27) and improvements in chest expansion (0.31), fitness (0.32), HAQ-S (0.29), and stiffness (0.33). Regression analysis revealed 2 significantly explanatory steps: changes in fitness explained 16% of total variance of changes in global health, and changes in stiffness contributed an additional 11%.(ABSTRACT TRUNCATED AT 250 WORDS)
Fourteen patients with ankylosing spondylitis (AS) were treated in a pilot study for two weeks at a Tiberias spa with a combination of hot mineral water baths and mud packs. A significant improvement was noticed in morning stiffness, finger to floor distance and the overall well-being assessment both by the patient and the physician. A significant reduction in the use of analgesics and NSAIDs was also noted in most of the patients. Improvement in all parameters began after one week of treatment and was still present at three months.
To test the safety and efficacy of olsalazine in men with ankylosing spondylitis (AS) unresponsive to nonsteroidal antiinflammatory drugs and physiotherapy.
Four patients, including 2 who had not responded to sulfasalazine (SASP) and one who did not tolerate SASP, were treated with olsalazine, up to 3 g/dl for 24 weeks.
One patient discontinued olsalazine due to diarrhea at 1 g/day. The other 3 experienced improvement in global spine self assessment by visual analog scale (VAS), 2 of 3 patients, spinal pain (VAS, 3 of 3), night pain (3 of 3), tender joint count (3 of 3) and enthesis score (3 of 3). Changes in Schober's test and chest expansion were minor. Erythrocyte sedimentation rate and C-reactive protein were normal. Loose stools were the only adverse effects observed.
Olsalazine appears to be well tolerated and effective in men with AS. Further study of olsalazine and direct comparison with SASP in this population may illuminate mechanisms of drug action and add a new therapeutic option.
To determine the predictive factors of outcome in patients with spondyloarthropathy (European Spondyloarthropathy Study Group or Amor criteria) monitored by a single investigator.
Classification of longterm outcome on a 3-grade scale. Candidate predictive factors: presence or not of 12 clinical or biological variables during the first 2 years of the disease, collected by history at the time of the first visit. Univariate analysis to pick up the factors statistically correlated with severity and then odds ratio and 95% confidence interval (CI) for each variable were calculated.
Of the 328 patients with spondyloarthropathy, 151 had a followup of > or = 10 years and minor disease (81), severe (28), or moderate disease (42). Seven variables at entry were correlated with disease severity (odds ratio; CI 95%); hip arthritis (22.85; 4.43-118); erythrocyte sedimentation rate > 30 mm/h (7; 4.84-9.50); poor efficacy of nonsteroidal antiinflammatory drugs (8.33; 2.56-27.10); limitation of lumbar spine (7; 2-25); sausage-like finger or toe (8.45; 1.48-9); oligoarthritis (4.25; 1.38-13.10); onset < or = 16 years (3.47; 1.06-12.75). If none of these factors is present at entry a mild outcome can be predicted (sensitivity: 92.5%; specificity: 78%). If a hip is involved or if 3 factors are present, a severe outcome is predictable (sensitivity: 50%) and a mild disease practically excluded (specificity: 97.5%).
Predictive factors of poor or benign longterm outcome could be defined very early after onset of spondyloarthropathy in a set of patients monitored by one observer.
The literature concerning second-line treatment of seronegative spondylarethropathies from 1940 to August 1993 was reviewed. Sulfasalazine appeared to be effective in the treatment of ankylosing spondylitis (AS) and promising in reactive arthritis (ReA) and Reiters' syndrome (RS). Methotrexate and azathioprine were associated with a remarkable improvement in some cases of AS and RS. Methylprednisolone and levamisole were both efficacious in AS, but levamisole was associated with occasional severe side effects. Radiation therapy led to short-term improvement in AS, but was abandoned because of severe long-term side effects. Only sulfasalazine has been studied in sufficient detail to allow definitive conclusions, but methotrexate and azathioprine may be promising drugs.
Ximoprofen is a new propionic NSAID which has previously demonstrated its efficacy at a daily dose of 30 mg. The aim of the study was to evaluate the efficacy of different daily dosages of Ximoprofen in patients with active ankylosing spondylitis. For 2 weeks 5 parallel groups were studied: placebo and Ximoprofen at 5, 10, 20 and 30 mg daily. Response to treatment was defined as an improvement in pain (VAS 100 mm) of at least 50% during the study. 285 out of the 332 screened patients were included. At the end of the study, the percentage of responders was higher in the Ximoprofen groups (54%, 41%, 53%, 56% in the 5, 10, 20 and 30 mg groups, respectively) than in the placebo group (21%). The clearest dose related effect of Ximoprofen observed occurred after one week of treatment. This study 1/confirms the efficacy of Ximoprofen at a 30 mg daily dosage, 2/shows the persistence of this efficacy at lower dosages, 3/suggests that ankylosing spondylitis is a sensitive and relevant human model to assess NSAIDs at an early stage of clinical evaluation.
To study the effects of adding supervised group physical therapy to unsupervised individualized therapy in ankylosing spondylitis.
One hundred forty-four patients were randomized to exercises at home, or the same plus weekly group physical therapy for 9 months. Endpoints were spinal mobility, fitness (maximum work capacity by ergometry), functioning (Sickness Impact Profile, Health Assessment Questionnaire for the Spondylarthropathies, and Functional Index), and patient's global assessment of change on a 10-cm visual analogue scale.
Thoracolumbar flexion and extension increased by an average of 0.5 cm (9%) after home exercises, and by 0.9 cm (16%) after group therapy. Maximum load in ergometry decreased by 2 W (1%) after home exercises, but increased by 7 W (4%) after group therapy. Global assessment improved by 0.3 (6%) after home exercises, and by 1.7 (34%) after group therapy. These three differences were statistically significant. There were no significant differences in chest expansion, cervical rotation, or the self-assessments of functioning.
Group physical therapy proved superior to individualized therapy in improving thoracolumbar mobility and fitness, and had an important effect on global health reported by the patients.
Physical therapy in ankylosing spondylitis (AS) is considered important for maintaining or improving mobility, fitness, functioning, and global health. We studied the influence of disease duration on the short term effects of supervised individual therapy. One hundred forty-four AS outpatients (modified New York Criteria; mean age: 43 years; median duration of disease: 4 years; range: 0-33) received 12 supervised individual treatments in a 6-week course of 30 minutes. Endpoints were: spinal mobility (thoracic and lumbar flexion and extension, chest expansion, cervical rotation), fitness (maximum work capacity by ergometry), functioning (Sickness Impact Profile (SIP) and the Functional Index (FI)), and global patient assessment of change on a visual analogue scale. After 6 weeks patients had improved in all endpoints, but only significantly in rotation (8 degrees, 10%), fitness (6 watt, 4%), and SIP (0.6, 14%; t-test, p < 0.05). Global patient assessment improved by 1.1 (22%). Plots of change scores and disease duration showed no evident relation. We also divided the population into two groups, with the median disease duration as a cut-off. No relevant difference in improvement was found between 'short duration' and 'long duration' groups (t-test of change scores, p > 0.05). In addition, no relevant correlation was found between change scores and disease duration (p > 0.01). It may be concluded that irrespective of disease duration, short term supervised individual therapy is effective in AS, slightly improving mobility, fitness, functioning and global health.
In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.