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ABSTRACT: OBJECTIVE: To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN. METHODS: Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.4. ALT was measured every three months. With logistic regression analyses, baseline variables predictive of first ALT of >2× ULN were identified and the association between use of concomitant antirheumatic drugs, the actual and cumulative dose of MTX and ALT of >2× ULN was determined. RESULTS: In total, 498 patients ever initiated MTX, with a total duration on MTX of 1,416 patient-years. In 89 patients, a first incidence of ALT of >2× ULN occurred. Incidence rate was 6.3 per 100 patient-years and cumulative incidence 18 %. ACPA positivity and baseline ALT of >1× ULN were independent predictors of later ALT of >2× ULN (OR 1.8 (95 % CI, 1.1-3.1) and OR 3.1 (95 % CI, 1.6-6.2), respectively). Smoking showed a trend (OR 1.6 (95 % CI, 0.98-2.7)). Mean MTX dosage over time was higher in patients with an ALT of >2× ULN. Patients who did not have an ALT of >2× ULN used more concomitant disease-modifying antirheumatic drugs and longer. CONCLUSIONS: In RA patients treated with MTX according to a dynamic strategy resembling daily clinical practice, incidence of increased ALT of >2× ULN was lower than previously reported, and also without treatment adjustments, persistence was rare. The recommendations for ALT monitoring may be reevaluated.
Clinical Rheumatology 12/2012; · 2.00 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the contribution of joint space narrowing (JSN) and erosions in general and in four different joint groups in relation to physical disability in rheumatoid arthritis (RA). METHODS: 5-year follow-up data from the Behandel Strategieën (BeSt) trial were used, where 508 patients with recent onset RA were treated aiming at a disease activity score ≤2.4. Joint damage was assessed annually and scored according to the Sharp-van der Heijde method. Physical disability was measured 3-monthly with the Health Assessment Questionnaire (HAQ). Generalised Estimating Equations analyses were performed to assess the relationship between the HAQ and JSN scores and erosions scores, separately and in joint groups. RESULTS: Overall, damage scores were low, and neither total JSN nor erosions showed a significant effect on HAQ (β=0.001 95% CI -0.003 to 0.004 and β=0.002 95% CI -0.001 to 0.006, respectively). Of the total damage scores per joint group, damage in the wrist shows a trend for association with physical disability displaying the largest effect size (β=0.005 95% CI 0.000 to 0.011). Also in the analysis with erosions per joint group, the wrist was most strongly related with physical functioning (β=0.016 95% CI 0.003 to 0.029); in the analysis with JSN per joint group no joint group was significantly related to the HAQ. Analysis of all erosion and narrowing scores per joint group in one model reveals only erosions in the wrist to be independently associated with impaired physical functioning (β=0.017 95% CI 0.003 to 0.030). CONCLUSIONS: Joint damage in the wrist, erosions more than JSN, is associated with impaired physical functioning even in patients with early RA with limited overall damage after 5 years tightly controlled treatment.
Annals of the rheumatic diseases 06/2012; · 8.11 Impact Factor
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ABSTRACT: Several prediction models for rapid radiological progression (RRP) in the first year of rheumatoid arthritis have been designed to aid rheumatologists in their choice of initial treatment. The association was assessed between RRP and disability and joint damage progression in 8 years.
Patients from the BeSt cohort were used. RRP was defined as an increase of ≥5 points in the Sharp/van der Heijde score (SHS) in year 1. Functional ability over 8 years, measured with the health assessment questionnaire (HAQ), was compared for patients with and without RRP using linear mixed models. Joint damage progression from years 1 to 8 was compared using logistic regression analyses.
RRP was observed in 102/465 patients. Over 8 years, patients with RRP had worse functional ability: difference in HAQ score 0.21 (0.14 after adjustment for disease activity score (over time)). RRP was associated with joint damage progression ≥25 points in SHS in years 1-8: OR 4.6.
RRP in year 1 is a predictor of worse functional ability over 8 years, independent of baseline joint damage and disease activity. Patients with RRP have more joint damage progression in subsequent years. RRP is thus a relevant outcome on which to base the initial treatment decision.
Annals of the rheumatic diseases 04/2012; 71(9):1530-3. · 8.11 Impact Factor
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ABSTRACT: Anticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment in patients with RA positive or RA negative for ACPA.
In the BehandelStrategieën (BeSt) study, 508 patients with recent-onset RA were randomised to four treatment strategies aimed at a DAS ≤2.4. Risks of damage progression and (drug-free) remission in 8 years were compared for ACPA-positive and ACPA-negative patients using logistic regression analysis. Functional ability and DAS components over time were compared using linear mixed models.
DAS reduction was achieved similarly in ACPA-positive and ACPA-negative patients in all treatment strategy groups, with a similar need to adjust treatment because of inadequate response. Functional ability and remission rates were not different for ACPA-positive and ACPA-negative patients. ACPA-positive patients had more radiological damage progression, especially after initial monotherapy. They had a lower chance of achieving (persistent) drug-free remission.
Clinical response to treatment was similar in ACPA-positive and ACPA-negative patients. However, more ACPA-positive patients, especially those treated with initial monotherapy, had significant radiological damage progression, indicating that methotrexate monotherapy and DAS- (≤2.4) steered treatment might be insufficient to adequately suppress joint damage progression in these patients.
Annals of the rheumatic diseases 11/2011; 71(2):245-8. · 8.11 Impact Factor
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ABSTRACT: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors?
Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation.
At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles.
In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient.
Scandinavian journal of rheumatology 11/2011; 41(1):15-9. · 2.51 Impact Factor
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ABSTRACT: To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission.
mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 ≥ DAS ≤ 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified.
Mean change in mBMD in CR patients was -0.03%, compared to -3.13% and -2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to -4.6 mg/cm2/year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (≥4.6 mg/cm2/year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0-18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain.
In RA, mBMD gain occurs primarily in patients in continuous (≥1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.
Arthritis care & research. 09/2011; 63(12):1691-9.
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ABSTRACT: To describe the disease course after the cessation of infliximab in early rheumatoid arthritis patients with disease activity score (DAS)-steered treatment and to identify predictors of persistent low disease activity.
In a post-hoc analysis of the BeSt study, disease activity and joint damage progression were observed in patients treated with methotrexate plus infliximab, who discontinued infliximab after achieving low disease activity (DAS ≤2.4) for 6 months. Predictors were identified using Cox regression analysis.
104 patients discontinued infliximab, of whom 77 had received infliximab plus methotrexate as initial treatment. Mean DAS at the time of infliximab cessation was 1.3, median symptom duration was 23 months and median Sharp/van derHeijde score was 5.5. The median follow-up was 7.2 years. Infliximab was re-introduced after loss of low disease activity in 48%, after a median of 17 months. The joint damage progression rate did not increase in the year after cessation, regardless of flare. After re-introduction of infliximab, 84% of these patients again achieved a DAS ≤2.4. In the multivariable model, smoking, infliximab treatment duration ≥18 months and shared epitope (SE) were independently associated with the re-introduction of infliximab: 6% of the non-smoking, SE-negative patients treated <18 months needed infliximab re-introduction.
Cessation of infliximab was successful in 52%, with numerically higher success rates in patients initially treated with infliximab. Of the 48% who flared, 84% regained low disease activity. The joint damage progression rate did not increase in the year after cessation. Smoking, long infliximab treatment duration and SE were independently associated with re-introduction of infliximab.
Annals of the rheumatic diseases 04/2011; 70(8):1389-94. · 8.11 Impact Factor
