Stouten Veerle, Michiels Stijn, Westhovens René, De Cock Diederik, Belba Amy, Pazmino Sofia, Van der Elst Kristien, Joly Johan, Verschueren Patrick
KU Leuven, Department of Development and Regeneration, Skeletal Biology and Engineering Research Centre, Herestraat 49, 3000, Leuven, Belgium.
University Hospitals Leuven, Division of Rheumatology, 3000, Leuven, Belgium.
Clin Rheumatol. 2020 Sep;39(9):2593-2601. doi: 10.1007/s10067-020-05008-4. Epub 2020 Mar 12.
INTRODUCTION/OBJECTIVES: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking.
The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP < 2.6) at week 65 counted from re-randomization, as well as drug retention rates and safety during the 65 weeks of follow-up, were compared.
Remission rates at week 65 after re-randomization were numerically higher in patients assigned to MTX (29/32; 90.6%) compared with patients on LEF (20/27; 74.1%) (p = 0.091). Of patients assigned to MTX, 60% (19/32) maintained LDA while continuing their assigned monotherapy until week 65 after re-randomization versus 44% (12/27) in the LEF group (p = 0.25). Patients re-randomized to MTX were more frequently in LDA measured by Clinical Disease Activity Index (32/32; 100%) compared with patients on LEF (23/27; 85.2%) (p = 0.024) 65 weeks after re-randomization. According to survival analyses, the probability of maintaining MTX monotherapy was higher (81%) than maintaining LEF monotherapy (55%) for 65 weeks (p = 0.025) after re-randomization. Safety analysis after re-randomization showed a good safety profile in both groups.
MTX monotherapy seems not significantly more efficacious as maintenance treatment compared with LEF monotherapy but has a better retention rate and is well tolerated in early RA patients in LDA after combination therapy with both.
Clinical trials NCT01172639 Key points • Methotrexate should be preferred over leflunomide as maintenance therapy after an initial intensive combination of these two drugs. • Methotrexate shows a better retention rate to leflunomide as maintenance therapy in this context.
引言/目的：目前缺乏关于逐步递减策略对甲氨蝶呤（MTX）和来氟米特（LEF）联合治疗病情得到良好控制的早期类风湿关节炎（RA）患者有效性的证据。
早期类风湿关节炎护理（CareRA）试验是一项为期2年的随机实用试验，比较初治早期RA患者不同的缓解诱导策略。在本研究中，我们纳入了在开始MTX、LEF和泼尼松桥接方案联合治疗后40至52周达到低疾病活动度（LDA）（DAS28-CRP≤3.2），随后采用达标治疗方法的参与者。患者被重新随机分组，接受每周15mg MTX或每日20mg LEF的维持单药治疗。比较从重新随机分组起第65周的缓解率（DAS28-CRP<2.6），以及随访65周期间的药物留存率和安全性。
重新随机分组后第65周，分配至MTX组的患者缓解率（29/32；90.6%）在数值上高于LEF组患者（20/27；74.1%）（p=0.091）。分配至MTX组的患者中，60%（19/32）在重新随机分组后继续接受指定单药治疗直至第65周时维持LDA，而LEF组为44%（12/27）（p=0.25）。重新随机分组后65周，通过临床疾病活动指数测量，重新随机分组至MTX组的患者处于LDA的频率更高（32/32；100%），高于LEF组患者（23/27；85.2%）（p=0.024）。根据生存分析，重新随机分组后65周，维持MTX单药治疗的概率（81%）高于维持LEF单药治疗（55%）（p=0.025）。重新随机分组后的安全性分析显示两组安全性良好。
与LEF单药治疗相比，MTX单药治疗作为维持治疗似乎并无显著更高的疗效，但在联合治疗后处于LDA的早期RA患者中，MTX留存率更高且耐受性良好。
临床试验NCT01172639要点•在这两种药物初始强化联合治疗后，作为维持治疗，MTX应优先于LEF。•在此背景下，作为维持治疗，MTX的留存率优于LEF。
