C J Haagsma

Ziekenhuisgroep Twente, Almeloo, Overijssel, Netherlands

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Publications (29)119.69 Total impact

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    ABSTRACT: INTRODUCTION: Ultrasonography (US) might have an added value to clinical examination in diagnosing early rheumatoid arthritis (RA) and assessing remission of RA. We aimed to clarify the added value of US in RA in these situations performing a systematic review. METHODS: A systematic literature search was performed for RA, US, diagnosis and remission. Methodological quality was assessed; the wide variability in the design of studies prohibited pooling of results. RESULTS: Six papers on the added value of US diagnosing early RA were found, in which at least bilateral metacarpophalangeal (MCP), wrists and metatarsophalangeal (MTP) joints were scanned. Compared to clinical examination US was superior with regard to detecting synovitis and predicting progression to persistent arthritis or RA. Eleven papers on assessing remission were identified, in which at least the wrist and the MCP joints of the dominant hand were scanned. Often US detected inflammation in patients clinically in remission, irrespective of the remission criteria used. Power Doppler signs of synovitis predicted X-ray progression and future flare in patients clinically in remission. CONCLUSIONS: US appears to have added value to clinical exam for diagnosing of RA when scanning at least MCP, wrist and MTP joints, and, when evaluating remission of RA, scanning at least wrist and MCP joints of the dominant hand. For both purposes primarily Power Doppler US might be used since its results are less equivocal than those of greyscale US.
    Arthritis research & therapy 01/2013; 15(1):R4. · 4.27 Impact Factor
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    ABSTRACT: There is strong evidence from clinical trials that a 'treat to target' strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 <2.6 is more effective than 'usual care' treatment for reaching clinical remission after 1 year. Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28<2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with -2.5 in tight control and -1.5 in usual care (p<0.0001). In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.
    Annals of the rheumatic diseases 12/2011; 71(6):845-50. · 8.11 Impact Factor
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    ABSTRACT: Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat-to-target strategy aimed at achieving remission in very early RA in daily clinical practice. Five hundred thirty-four patients with a clinical diagnosis of very early RA were included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Treatment adjustments were based on the Disease Activity Score in 28 joints (DAS28), aiming at a DAS28 of <2.6 (methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with biologic agents in case of persistent disease activity). The primary outcome was disease activity after 6 months and 12 months of followup, according to the DAS28, the European League Against Rheumatism (EULAR) response criteria, and the modified American College of Rheumatology (ACR) remission criteria. Secondary outcomes were time to first DAS28 remission and outcome of radiography. Six-month and 12-month followup data were available for 491 and 389 patients, respectively. At 6 months, 47.0% of patients achieved DAS28 remission, 57.6% had a good EULAR response, and 32.0% satisfied the ACR remission criteria. At 12 months, 58.1% of patients achieved DAS28 remission, 67.9% had a good EULAR response, and 46.4% achieved ACR remission. The median time to first remission was 25.3 weeks (interquartile range 13.0-52.0). The majority of patients did not have clinically relevant radiographic progression after 1 year. The successful implementation of this treat-to-target strategy aiming at remission demonstrated that achieving remission in daily clinical practice is a realistic goal.
    Arthritis & Rheumatology 06/2011; 63(10):2865-72. · 7.48 Impact Factor
  • Rheumatology. 01/2011;
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    ABSTRACT: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) < or =0.30 mmol/l (5 mg/dl). A randomised, controlled, open-label, multicentre trial in gout patients with renal function defined as a calculated creatinine clearance > or =50 ml/min. Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day (stage 1). If sUr < or =0.30 mmol/l was not attained after 2 months, the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day (stage 2). The primary end point was treatment success in either of the two stages, defined as clinical tolerability and attainment of biochemical target sUr. Sixty-five patients were enrolled in stage 1; 36 received allopurinol and 29 received benzbromarone. Fifty-five patients (85%) were analysed at stage 1: the success rates were 8/31 (26%) and 13/25 (52%), respectively, and the difference was -0.26 (95% CI from -0.486 to -0.005), p = 0.049. At stage 2, the success rates were 21/27 (78%) and 18/23 (78%), respectively, and the difference was -0.005 (95% CI from -0.223 to 0.220), p = 1.00. Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions. Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates (both 78% successful in attaining sUr < or =0.30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation. Trial registration number: ISRCTN49563848).
    Annals of the rheumatic diseases 06/2009; 68(6):892-7. · 8.11 Impact Factor
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    ABSTRACT: To study the bioavailability of a divided higher oral dose of methotrexate (MTX), in comparison to a single dose, in adult patients with rheumatoid arthritis (RA). A pharmacokinetic analysis was performed in 10 patients with RA taking a stable dose (25-35 mg weekly) of MTX. Separated by one week, a pharmacokinetic analysis was performed in each patient after an oral single dose, and after an equal but split dose separated by 8 hours. MTX serum concentrations were measured by a fluorescence polarization immunoassay technique. Analysis was performed by calculation of the area under the curve (AUC) by the trapezoidal rule and by means of an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. For the population analysis, data from 15 patients in our previous study comparing oral and subcutaneous administration of MTX were also used. The median MTX dose was 30 mg weekly (range 25-35 mg). The bioavailability of the split dose was 28% higher compared to the single dose (p = 0.007). In the population pharmacokinetic modeling, a 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after single-dose and split-dose MTX was 0.76 and 0.90, respectively, compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 oral administration regimens (p = 0.008). The bioavailability of oral higher dose MTX in adult patients with RA can be improved by splitting the dose.
    The Journal of Rheumatology 04/2006; 33(3):481-5. · 3.26 Impact Factor
  • H Baan, C J Haagsma, M A F J van de Laar
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    ABSTRACT: Symptomatic rheumatoid nodules are frequently surgically treated. Injection with steroids might be an alternative treatment. To determine whether injection with triamcinolon acetonide reduces the size of rheumatoid nodules, we randomized twenty patients with symptomatic nodules to either triamcinolon acetonide 40 mg/ml plus lidocaine 2% or lidocaine 1% (placebo). We measured the nodules before injection and 2, 4, 8, and 12 weeks after injection. Possible side effects were recorded. We found that the volume of the nodules injected with triamcinolon acetonide reduced significantly (p = 0.011), from 130 to 8 mm(3) (median calculated size) at 12 weeks, compared with baseline. Furthermore, at 12 weeks, the difference between the groups was significant (p = 0.03). The median size of the placebo nodules diminished as well, from 358 to 237 mm(3), but this was not significant. Pain at injection was the only side effect, equally distributed in both treatment groups. Injection with triamcinolon acetonide seems to be an alternative for surgery of rheumatoid nodules. No adverse events occurred but the limited sample does not allow definitive conclusions.
    Clinical Rheumatology 03/2006; 25(1):21-3. · 2.04 Impact Factor
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    ABSTRACT: To investigate the effect of higher weekly maintenance dose methotrexate (MTX) (> or =25 mg/week) on plasma homocysteine concentrations in adults with RA. Patients with RA were treated with high doses of MTX with adjuvant folic acid. Plasma homocysteine was determined at baseline and 1, 2, 4, 8, 12, and 48 hours after subcutaneous MTX administration. Maximum homocysteine concentrations after MTX administration were compared with baseline concentrations. Fifteen patients with RA (11 women) were included, with a median age of 61 years (range 31-72) and median disease duration 7 years (range 2-32). Median MTX dose was 30 mg (range 25-40). All patients received folic acid supplementation (5-30 mg/week). Median plasma homocysteine concentration at baseline was 10.1 mumol/l (range 6.6-12.7; normal 6-15). Homocysteine concentrations increased after MTX administration by a median of 2.5 mumol/l (range 0.7-5.1). Median maximum plasma homocysteine was significantly higher than at baseline. Peak homocysteine was reached after 12 hours. No relation between serum folate concentrations and plasma homocysteine concentrations was found. In patients with RA higher MTX doses with adjuvant folic acid do not increase baseline concentrations of homocysteine. An intermittent significant rise in plasma homocysteine occurs in the 48 hours after MTX administration.
    Annals of the Rheumatic Diseases 02/2005; 64(1):141-3. · 9.11 Impact Factor
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    ABSTRACT: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic analysis was performed in each patient after oral and subcutaneous administration of the same dose of MTX. MTX serum concentrations were measured by a fluorescence polarization immunoassay. Pharmacokinetic analysis was performed with an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. The median MTX dose was 30 mg weekly (range 25-40 mg). A 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after oral MTX was 0.64 (range 0.21-0.96) compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 administration regimens. Bioavailability of a higher oral dose of MTX in adult patients with RA is highly variable, and on average two-thirds that of the subcutaneous administration. To improve efficacy of MTX at dosages of 25 mg weekly or more, a change to parenteral administration should be considered.
    The Journal of Rheumatology 05/2004; 31(4):645-8. · 3.26 Impact Factor
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    ABSTRACT: To study which factors are associated with longterm methotrexate (MTX) use in rheumatoid arthritis (RA). All patients with RA who had started MTX after January 1, 1993, were selected from a regional hospital based registration system. Data on demographic and clinical features were retrieved through chart review. By means of life table analysis and Cox regression analysis, MTX survival and the relation between demographic variables, clinical features, and MTX survival were studied. A total of 1072 MTX treatment episodes in 1022 patients were analyzed. The cumulative MTX survival probability after 5 years was 64%, and after 9 years was 50%. Univariate analysis showed a significant relation between MTX survival probability and folic acid supplementation, attending rheumatologist, concurrent prednisolone use, concurrent sulfasalazine use, and the number of previous disease modifying drugs. In the multivariate analysis folic acid supplementation, attending rheumatologist, and concurrent prednisolone use remained significantly related to MTX survival. Age, disease duration, and creatinine clearance were not. In this retrospective study of 1022 patients with RA the cumulative MTX survival probability was 64% after 5 years and 50% after 9 years. Folic acid supplementation and to a lesser extent prednisolone were associated with a longer MTX survival. In addition, treatment strategies of individual rheumatologists influenced MTX survival.
    The Journal of Rheumatology 12/2003; 30(11):2325-9. · 3.26 Impact Factor
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    ABSTRACT: To study factors associated with toxicity, final dose, and efficacy of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Data were used from a randomised clinical 48 week trial on 411 patients with RA all treated with MTX, comparing folates and placebo. Logistic regression was used to study the relation between baseline variables and various dependent factors, including hepatotoxicity (alanine aminotransferase >/=3 x upper limit of normal), MTX withdrawal, final MTX dose >/=15 mg/week, and MTX efficacy. Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity. Next to this, high body mass index was related to the occurrence of hepatotoxicity. Prior gastrointestinal (GI) events and younger age were related to the adverse event, diarrhoea. Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal, which in turn was associated with the absence of folate supplementation, body mass index, prior GI events, and female sex. Renal function (creatinine clearance >/=50 ml/min) was not associated with toxicity. Reaching a final dose of MTX of >/=15 mg/week was related to folate supplementation and the absence of prior GI events. Efficacy of MTX treatment was associated with low disease activity at baseline, male sex, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lower creatinine clearance. MTX toxicity, final dose, and efficacy are influenced by folate supplementation. Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.
    Annals of the Rheumatic Diseases 05/2003; 62(5):423-6. · 9.11 Impact Factor
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    ABSTRACT: To study (i) the influence of methotrexate (MTX) therapy on homocysteine and folate metabolism in patients with rheumatoid arthritis (RA), (ii) the influence of the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) on the change in plasma homocysteine levels during MTX treatment, and (iii) the interference of folate and homocysteine metabolism with the efficacy and toxicity of treatment with MTX. The 113 patients enrolled in this study were participating in a 48-week, multicentre, double-blind, placebo-controlled study comparing the efficacy and toxicity of MTX treatment with and without folic or folinic acid supplementation. The MTX dose was 7.5 mg/week initially and increased to a maximum of 25 mg/week if necessary. Concentrations of total folate, 5-methyl tetrahydrofolate (in serum and in erythrocytes) and of homocysteine, cysteine and cysteine-glycine and the MTHFR genotype were determined before the start of the study, after 6 weeks, and after 48 weeks or on withdrawal from the study. Blood was drawn from fasting patients at a standardized time in the morning, 16 h after intake of MTX. The laboratory results were related to parameters of efficacy and toxicity of MTX treatment. Baseline values were distributed equally in the three treatment groups. The mean plasma homocysteine level (normal range 6-15 micromol/l) before the start of MTX was relatively high in all groups: 15.4 micromol/l [95% confidence interval (CI) 13.5 to 17.2] in the MTX plus placebo group (n=39), 14.3 micromol/l (95% CI 12.2 to 16.4) in the MTX plus folic acid group (n=35) and 15.9 micromol/l (95% CI 13.7 to 18.1) in the MTX plus folinic acid group (n=39). After 48 weeks of MTX therapy, the mean homocysteine level showed an increase in the placebo group (+3.6 micromol/l, 95% CI 1.7 to 5.6). In contrast, a decrease was observed in the groups supplemented with folic or folinic acid (folic acid, -2.7 micromol/l, 95% CI -1.4 to -4.0; folinic acid, -1.6 micromol/l, 95% CI -0.1 to -3.0). The differences in the change in plasma homocysteine level between the placebo group and each of the two folate-supplemented groups were statistically significant (P<0.0001), contrary to the difference between the folic and folinic acid groups (P=0.26). Linear regression analysis showed that the change in plasma homocysteine level was statistically significantly associated with folic or folinic acid supplementation (P=0.0001) but not with the presence or absence of the C677T mutation in the MTHFR gene. Homozygous mutants had a higher plasma homocysteine concentration at baseline. No relationship was found between the change in disease activity and the change in homocysteine concentration or the mean homocysteine concentration after 48 weeks of MTX therapy. Toxicity-related discontinuation of MTX treatment was not associated with the change in homocysteine concentration. Low-dose MTX treatment in RA patients leads to an increased plasma homocysteine level. Concomitant folate supplementation with either folic or folinic acid decreases the plasma homocysteine level and consequently protects against potential cardiovascular risks. No relationship was found between the change in homocysteine concentration and the presence or absence of the C677T mutation in the MTHFR gene. Homocysteine metabolism was not associated with efficacy or toxicity of MTX treatment.
    Rheumatology 06/2002; 41(6):658-65. · 4.21 Impact Factor
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    ABSTRACT: To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA). Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment. Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation. The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.
    Arthritis & Rheumatology 12/2001; 44(11):2525-30. · 7.48 Impact Factor
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    ABSTRACT: Objective To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment.ResultsForty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation.Conclusion The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.
    Arthritis & Rheumatology 10/2001; 44(11):2525 - 2530. · 7.48 Impact Factor
  • P L van Riel, C J Haagsma, D E Furst
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    ABSTRACT: Pharmacotherapy is still the cornerstone in the management of rheumatoid arthritis (RA). Due to several reasons the pharmacotherapeutic strategy has changed dramatically in the past decades. It has become clear that in most cases single treatment with disease modifying antirheumatic drugs (DMARDs) is insufficient to control the disease on the long term. This is the main reason why combinations of second-line agents are increasingly being used in the treatment of established RA. Many different ways of prescribing combination treatment and a large number of different combinations have been published. However definite conclusions which drugs to combine or what strategy to apply are difficult to make as solid studies which enable these conclusions are sparse. Several studies have shown that the best opportunity to achieve a good response is to use a set-up approach, in addition different studies have shown that corticosteroids do have a profound effect on disease activity variables.
    Bailli&egrave re s Best Practice and Research in Clinical Rheumatology 01/2000; 13(4):689-700. · 3.55 Impact Factor
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    ABSTRACT: We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.
    The Journal of Rheumatology 04/1999; 26(3):705-11. · 3.26 Impact Factor
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    ABSTRACT: To study the influence of sulphasalazine (SSZ), methotrexate (MTX), and the combination (COMBI) of both on plasma homocysteine and to study the relation between plasma homocysteine and their clinical effects. 105 patients with early rheumatoid arthritis (RA) were randomised between SSZ (2-3 g/day), MTX (7.5-15 mg/week), and the COMBI (same dose range) and evaluated double blindly during 52 weeks. Plasma homocysteine, serum folate concentrations, and vitamin B12 were measured. The influence of the C677T mutation of the enzyme methyl-enetetrahydrofolatereductase (MTHFR) gene was analysed. A slight trend towards increased efficacy and an increased occurrence of minor gastrointestinal toxicity was present in the COMBI group, no differences existed clinically between SSZ and MTX. Only a slight and temporary increase in plasma homocysteine was found in the SSZ group, in contrast with the persistent rise in the MTX group and the even greater increase in the COMBI patients. Patients homozygous for the mutation in the MTHFR gene had significantly higher baseline homocysteine, heterozygous MTHFR genotype induced a significantly higher plasma homoeysteine at week 52 compared with no mutation. No correlation was found between clinical efficacy variables and homocysteine. Patients with gastrointestinal toxicity had a significantly greater increase in homocysteine. A persistent increase in plasma homocysteine concentrations was observed in patients treated with MTX alone and more pronounced in combination with SSZ, in contrast with SSZ alone. An increase in plasma homocysteine is related to the C677T mutation in MTHFR. A relation in the change in homocysteine concentrations with (gastrointestinal) toxicity was found, no relation with clinical efficacy existed.
    Annals of the Rheumatic Diseases 03/1999; 58(2):79-84. · 9.11 Impact Factor
  • C J Haagsma
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    ABSTRACT: Rheumatic diseases are mostly chronic in nature and often require long term drug treatment. An increasing number of disease-modifying antirheumatic drugs (DMARDs) are used earlier in the course of disease and increasingly in combination with each other. Often there is comorbidity with ensuing pharmacotherapy, especially in the elderly, and therefore the risk of unwanted drug interactions increases. Awareness of these interactions is important in order to either avoid or manage them. Antimalarials, gold, penicillamine (D-penicillamine), sulfasalazine and azathioprine have few clinically important drug interactions. The renal excretion of the antifolate methotrexate is affected by drugs that influence kidney function. This is of particular importance in patients with compromised renal function, e.g. the elderly. Other drugs with influence on folate metabolism, such as trimethoprim, should not be given concomitantly. Cyclosporin is an agent recently introduced in rheumatological practice, and shows a myriad of clinically significant drug interactions mainly based on interference with its metabolic degradation by cytochrome P450 3A, leading to increased or decreased blood concentrations and toxicity or lack of effect. Although most of these interactions with cyclosporin are described in organ transplant patients, they may apply to rheumatological practice as well.
    Drugs & Aging 11/1998; 13(4):281-9. · 2.65 Impact Factor
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    ABSTRACT: To study the validity of response criteria for rheumatoid arthritis (RA) that included 28-joint counts instead of more comprehensive joint counts. In a double-blind, placebo-controlled trial of 105 patients treated with methotrexate, sulfasalazine, or both, response was evaluated at week 52. Both European League Against Rheumatism and American College of Rheumatology definitions of response, with comprehensive as well as simplified joint counts, were calculated. We studied the differences between the criteria with and without simplified joint counts, the discriminating capacity between treatment groups, and the association with change in functional capacity and joint damage. Response criteria that included 28-joint counts classified patients' responses more conservatively. No differences between treatment groups were found with either set of response criteria. The association with change in functional capacity was significant in all cases. All response criteria were significantly associated with radiographic progression of RA. Improvement criteria that include 28-joint counts are as valid as the original improvement criteria that included more comprehensive joint counts.
    Arthritis & Rheumatology 11/1998; 41(10):1845-50. · 7.48 Impact Factor
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    ABSTRACT: To compare the efficacy of sulphasalazine, methotrexate, and the combination of both in patients with early rheumatoid arthritis (RA), not treated with disease-modifying anti-rheumatic drugs previously, we conducted a double-blind, double-dummy, controlled, clinical trial. One hundred and five patients with active, early RA, rheumatoid factor and/or HLA DR1/4 positive were randomized between sulphasalazine (SSZ) 2000 (maximum 3000) mg daily, or methotrexate (MTX) 7.5 (maximum 15) mg weekly, or the combination (COMBI) of both, and were followed up by a single observer for 52 weeks. The mean change over time per patient, including all visits, in Disease Activity Score (DAS) was: SSZ: -1.6 (95% CI -2.0 to -1.2); MTX: -1.7 (-2.0 to -1.4); COMBI: -1.9 (-2.2 to -1.6); the difference week 0-week 52 (SSZ, MTX, COMBI respectively); DAS: -1.8, -2.0, -2.3, Ritchie articular index: -9.2, -9.5, -10.6, swollen joints: -9.2, -12.4, -14.3, erythrocyte sedimentation rate: -17, -21, -28. Nausea occurred significantly more in the COMBI group. The numbers of drop-outs due to toxicity were SSZ 9, MTX 2, COMBI 5. In conclusion, there were no significant differences in efficacy between combination and single therapy, only a modest trend favouring COMBI. The results of MTX and SSZ were very comparable. Nausea occurred more often in the COMBI group: the number of withdrawals due to adverse events did not differ significantly.
    British journal of rheumatology 11/1997; 36(10):1082-8.

Publication Stats

1k Citations
119.69 Total Impact Points

Institutions

  • 2013
    • Ziekenhuisgroep Twente
      Almeloo, Overijssel, Netherlands
  • 1998–2003
    • Medisch Spectrum Twente
      • Rheumatology Department
      Enschede, Overijssel, Netherlands
  • 1997–2001
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
    • Rijnstate Hospital
      Arnheim, Gelderland, Netherlands