Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
Clin Exp Rheumatol. 2013 Jul-Aug;31(4 Suppl 78):S14-8. Epub 2013 Oct 3.
Treat-to-target strategies in the management of patients with rheumatoid arthritis (RA) involve intensifying medication as long as low disease activity or remission is not achieved. Our aim was to discuss reasons and opportunities for tapering and discontinuing medication when the target is achieved, in particular of biological agents.
Data from the Behandel Strategieën (BeSt) study are presented, a multicentre randomised clinical trial comparing 4 treatment strategies in patients with recent onset active RA (1987 criteria): 1. Sequential monotherapy, 2. Step up to combination therapy (both starting with methotrexate (MTX) monotherapy), 3. Initial combination therapy with MTX, sulfasalazine and prednisone and 4. Initial combination therapy with MTX and infliximab. Treatment adjustments involving dose increases, drug changes or expansion to combination therapy occurred based on three-monthly calculations of the Disease Activity Score (DAS), with a target of ≤2.4. If this was achieved for 2 consecutive evaluations, treatment was tapered (combinations to monotherapy, monotherapy to maintenance dose). Prednisone and infliximab (either as part of initial treatment or as delayed treatment after failure on earlier therapies in arms 1, 2 and -for infliximab- 3) were always tapered and discontinued before other drugs. The outcomes of discontinuation of infliximab are presented.
77/120 (64%) of patients who started initial infliximab were able to discontinue infliximab, whereas 27/109 (25%) of patients who started delayed infliximab in arms 1-3 could discontinue infliximab. Discontinuation was independent of previous dose increases in order to achieve low DAS. After discontinuation of infliximab, 16 of 27 patients (59%) in arms 1-3 and 34 of 77 patients (44%) in arm 4 suffered a DAS flare >2.4 and had to restart treatment. Median time without infliximab treatment was 17 (IQR 3-47) months, and 29 of the 61 patients (58%) who needed to restart had been at least 1 year without infliximab. Restarting infliximab resulted in DAS ≤2.4 in all patients, and there was no progression of radiological damage. Presence of shared epitope, smoking, and a long treatment with infliximab were independent predictors of infliximab restart.
Data on infliximab discontinuation in the BeSt study suggest that this possible in 1 in 4 patients, or more if infliximab was the initial treatment, who have had at least 6 consecutive months of low disease activity. While MTX is continued, about 50% of patients can permanently stop infliximab without radiological damage progression, the others regain low disease activity after restarting infliximab. Treat to target strategies using biologic agents should include strategies for discontinuation.
针对类风湿关节炎（RA）患者的达标治疗策略包括，只要未达到低疾病活动度或缓解，就应加强药物治疗。我们的目的是讨论在达到目标时减少和停止药物治疗的原因和机会，特别是生物制剂。
介绍了 Behandel Strategieën（BeSt）研究的数据，这是一项多中心随机临床试验，比较了最近发病的活动性 RA 患者（1987 年标准）的 4 种治疗策略：1. 序贯单药治疗，2. 逐步联合治疗（均起始于甲氨蝶呤[MTX]单药治疗），3. MTX、柳氮磺胺吡啶和泼尼松初始联合治疗，4. MTX 和英夫利昔单抗初始联合治疗。根据每 3 个月计算的疾病活动评分（DAS），进行治疗调整，包括剂量增加、药物更换或联合治疗，目标为≤2.4。如果连续两次评估均达到此目标，则减少治疗（联合治疗转为单药治疗，单药治疗转为维持剂量）。泼尼松和英夫利昔单抗（无论是初始治疗的一部分，还是在第 1、2 组中在早期治疗失败后[在第 3 组中为英夫利昔单抗]延迟治疗）始终逐渐减少剂量并停药，然后再停其他药物。本文介绍了英夫利昔单抗停药的结果。
120 例起始英夫利昔单抗的患者中，有 77 例（64%）能够停用英夫利昔单抗，而在第 1-3 组中起始延迟英夫利昔单抗治疗的 109 例患者中，有 27 例（25%）能够停用英夫利昔单抗。停药与为达到低 DAS 而增加剂量无关。停用英夫利昔单抗后，第 1-3 组中有 27 例（59%）和第 4 组中有 77 例（44%）的 34 例患者 DAS 复发>2.4，需要重新开始治疗。无英夫利昔单抗治疗的中位时间为 17（IQR 3-47）个月，在需要重新开始治疗的 61 例患者中，有 29 例（58%）至少有 1 年未使用英夫利昔单抗。重新开始使用英夫利昔单抗后，所有患者的 DAS≤2.4，且无影像学损害进展。存在共享表位、吸烟和使用英夫利昔单抗时间较长是重新开始使用英夫利昔单抗的独立预测因素。
BeSt 研究中关于英夫利昔单抗停药的数据表明，在至少连续 6 个月低疾病活动度的患者中，约 1 例中有 1 例（如果英夫利昔单抗是初始治疗，则更多）可能停药。当继续使用 MTX 时，约 50%的患者可以在没有影像学损害进展的情况下永久性停用英夫利昔单抗，其余患者在重新开始使用英夫利昔单抗后可恢复低疾病活动度。使用生物制剂的达标治疗策略应包括停药策略。
