Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study

Abstract

Background: Tumour necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons.

Objective: To determine whether infliximab might be discontinued after achievement of LDA in patients with RA and to evaluate progression of articular destruction during the discontinuation.

Methods: 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score, including a 28-joint count (DAS28) was <3.2 (LDA) for 24 weeks, were studied.

Results: The mean disease duration of the 114 patients was 5.9 years, mean DAS28 5.5 and mean modified total Sharp score (mTSS) 63.3. After maintaining LDA for >24 weeks by infliximab treatment, the drug was discontinued and DAS28 in 102 patients was evaluated at year 1. Fifty-six patients (55%) continued to have DAS28<3.2 and 43% reached DAS<2.6 at 1 year after discontinuing infliximab. For 46 patients remission induction by Remicade in RA (RRR) failed: disease in 29 patients flared within 1 year and DAS28 was >3.2 at year 1 in 17 patients. Yearly progression of mTSS (DeltaTSS) remained <0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated DeltamTSS was 0.3 and 1.6 and Health Assessment Questionnaire-Disability Index was 0.174 and 0.614 in the RRR-achieved and RRR-failed groups, respectively, 1 year after the discontinuation.

Conclusion: After attaining LDA by infliximab, 56 (55%) of the 102 patients with RA were able to discontinue infliximab for >1 year without progression of radiological articular destruction.

Figure 1

Study design and profile. DAS28, Disease Activity Score, including a 28-joint count; IFX, infliximab; RRR, remission induction by Remicade in rheumatoid arthritis.

Figure 2

Changes of Disease Activity Score, including a 28-joint count (DAS28) in patients with remission induction by Remicade in rheumatoid arthritis-achieved (RRR-achieved) and patients for whom RRR failed (RRR-failed). (A) Changes of Disease Activity Score, including a 28-joint count (DAS28) at baseline when infliximab (IFX) was administered, at RRR-study entry when infliximab was discontinued and at the primary end point at week 52 after discontinuing IFX in 56 patients who were still satisfied with DAS28 (erythrocyte sedimentation rate (ESR)) <3.2 at week 52, RRR-achieved'. (B) Changes of DAS28 at baseline, at RRR entry and the end point in 46 patients whose disease activity flared after the discontinuation of IFX or DAS28 >3.2 at week 52, ‘RRR-failed’. The lower right panel shows changes of DAS28 after the restarting IFX in 32 patients for whom RRR failed.

Figure 3

Logistic analysis of probability of Disease Activity Score, including a 28-joint count (DAS28) was <3.2 at primary end point by DAS28 at remission induction by Remicade in rheumatoid arthritis entry (RRR entry). (A) Logistic regression analysis to estimate DAS28 at primary end point as dependent variables by DAS28 at RRR entry as independent variables. The y-axis shows the probability of DAS28 <3.2 at the primary end point after the 52 weeks discontinuation of infliximab and a scatter diagram of an individual patient and logistic regression curve (solid line) are shown. To attain DAS28 <3.2 at the end point in 50% of the 102 patients, DAS28 at RRR study entry was estimated by reciprocal statistics. (B) From the receiver operating characteristic curve based on the logistic regression analysis above, the cut-off point of DAS28 at RRR-study entry was 2.225. Subsequently, one-way analysis of DAS28 at the primary end point by DAS28 at study entry, <2.225 versus between 2.225 and 3.2, was performed and the statistical difference of the two groups was sought by non-parametric Wilcoxon t test (***p<0.001). ESR, erythrocyte sedimentation rate.

Figure 4

Health Assessment Questionnaire-Disability Index (HAQ-DI) in patients for whom remission induction by Remicade in rheumatoid arthritis failed (RRR-failed)' and in patients for whom ‘RRR was achieved (RRR-achieved)’ at (A) baseline, (B) RRR entry and (C) the primary end point. The line in the box represents the median value and the upper and lower ends of the box indicate the 25th and 75th centiles of the population. Statistical difference was assessed by non-parametric Wilcoxon t test.