Department of Internal Medicine, Fukushima Red Cross Hospital.
Department of Rheumatology, Hikarigaoka Spellman Hospital.
Fukushima J Med Sci. 2023 Apr 5;69(1):11-20. doi: 10.5387/fms.2022-06. Epub 2023 Mar 30.
Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients.
Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups.
The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01).
Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.
甲氨蝶呤（MTX）会引起广泛的副作用，包括骨髓抑制、间质性肺炎和感染。因此，对于类风湿关节炎（RA）患者，在使用托珠单抗（TCZ）和 MTX 联合治疗达到缓解后，确定是否需要继续使用 MTX 至关重要。因此，本多中心、观察性、队列研究的目的是评估 MTX 停药对这些患者安全性的可行性。
患者接受 TCZ 治疗，联合或不联合 MTX 治疗 3 年；选择接受 TCZ+MTX 联合治疗的患者。达到缓解后，一组患者停用 MTX（停药[DISC]组，n=33），另一组继续使用 MTX 且无疾病复发（维持[MAIN]组，n=37）。比较两组 TCZ+MTX 治疗的临床疗效、患者背景特征和不良事件。
DISC 组在第 3、6 和 9 个月时 28 个关节红细胞沉降率（DAS28-ESR）的疾病活动评分显著降低（P<0.05，P<0.01，P<0.01）。此外，DISC 组在第 6 和 9 个月时 DAS28-ESR 缓解率和第 6 个月时布尔缓解率显著更高（P<0.01）。DISC 组的疾病病程显著更长（P<0.05）。此外，DISC 组的 IV 期 RA 患者人数显著更多（P<0.01）。
尽管疾病病程较长且疾病进展到 IV 期，但对 TCZ+MTX 治疗反应良好的患者，一旦达到缓解，就可停用 MTX。
