Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation

Abstract

AimsTo determine factors predictive for leflunomide drug survival in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. MethodsA standard dataset was collected from medical records of consecutive outpatients on leflunomide treatment for rheumatoid arthritis between January 2000 and June 2003. The dataset consisted of patient, disease and treatment characteristics at the star t of leflunomide treatment, and data on leflunomide use. ResultsLeflunomide was started in 279 patients and 173 patients (62.0%) withdrew from treatment during follow-up. From univariate analysis, concomitant systemic corticosteroid use [hazard ratio (HR) (95% confidence interval) 1.35 (1.00, 1.83)] and an erythrocyte sedimentation rate < 35 mm h -1 [HR 1.38 (1.01, 1.88)] at start of leflunomide were found to be predictive for better leflunomide survival. Furthermore, the attending rheumatologist was correlated with leflunomide drug survival. Hazard ratios varied, depending on the individual rheumatologist, from 0.60 to 2.66. Multivariate analysis suggested attending rheumatologist (HR varying from 0.54 to 2.30 depending on the individual rheumatologist), concomitant systemic corticosteroid use [HR 1.58 (1.14 2.21)] and erythrocyte sedimentation rate < 35 mm h -1 [HR 1.42 (1.03, 1.96)] at start of leflunomide to be associated with leflunomide survival. ConclusionsConcomitant systemic corticosteroid use, erythrocyte sedimentation rate at the start of treatment and attending rheumatologist were found to be predictive for leflunomide survival. Information on these predictors at the start of leflunomide therapy may offer information on which patients are at an increased risk of withdrawal from leflunomide. Whether this information leads to optimization of leflunomide treatment outcomes remains to be studied. E. N. van Roon et al. 32060 :3 Br J Clin Pharmacol

Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?

“…found that ESR did not influence response to HCQ monotherapy [34] but in another study a low baseline CRP was the only predictor of a favorable response to HCQ monotherapy in early RA patients (OR (CRP ≤10 mg/L) = 3.6, 95% CI 2.2 to 6.0) [35]. van Roon and colleagues identified ESR <35 mm.h -1 at treatment start to predict higher leflunomide survival (hazard ratio (HR) = 1.38, 95% CI 1.01 to 1.88) [36] and likewise, high ESR at disease onset and at DMARD initiation predicted early discontinuation of treatment in an established RA study (HR = 1.05 per 10 mm.h -1 increase, 95% CI 1.02 to 1.08) [53]. Contrary to these findings, Capell et al .…”

“…RF is associated with persistent disease and radiographic progression [21,81-83] but its role in predicting response to treatment is less clear. A large number of studies, comprising a considerable number of patients, showed that RF status does not predict response to MTX and other DMARDs in both early and established RA [1,14,23,25,27-29,34,36,37,42,45,53,55,66,84]. However, in the study by Wessels et al [22] RF-positivity alone presented a trend towards worse response to MTX monotherapy in early RA patients; RF-positive smokers were definitely worse responders.…”

“…Serum creatinine levels were also demonstrated to be non-predictors of leflunomide treatment survival [36] but data on other DMARDs are even scarcer. High hemoglobin levels were associated with remission (DAS28 <2.6) at two years in the univariate analysis in early RA, DMARD-naïve patients.…”

Recent developments in anti-rheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis

“…Because of the very long half-life of the metabolite (about 2 weeks), a loading dose of 100 mg/day for 3 days (in adult-sized patients) is used to facilitate rapid attainment of steady-state levels. The onset of effect may begin as early as 4 weeks after drug initiation, and improvement continues through about 5 months of treatment [ 39 ].…”

Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthritis

“…Using multivariate analysis, a strong effect was seen for “attending rheumatologist”, suggesting that physician behavior in response to side effects is an important determinant. 135 …”