Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, ON, Canada.
Centre for Prognosis Studies in the Rheumatic Diseases, Krembil Research Institute, Toronto Western Hospital, University Health Network, 1E 416, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
Drugs. 2018 Apr;78(6):611-619. doi: 10.1007/s40265-018-0898-2.
Methotrexate is known to be safe and efficacious in the management of rheumatoid arthritis and psoriasis and thus has been used for the management of psoriatic arthritis despite a lack of evidence to support efficacy in psoriatic arthritis from randomized controlled trials. Although the largest randomized trial to date did not support its use as a disease-modifying therapy, observational studies have supported its role, and current treatment recommendations approve of its use as a first-line agent for the management of psoriatic arthritis with predominant peripheral arthritis. The first treat-to-target study in psoriatic arthritis, comparing tight control with standard care, has shown the efficacy of methotrexate as monotherapy in the first 12 weeks. This trial demonstrated the effectiveness of methotrexate with improvement in peripheral arthritis, skin and nail disease, enthesitis, and dactylitis over the course of 12 weeks. There is conflicting evidence about the role of combination (concomitant methotrexate and anti-tumor necrosis factor) therapy. However, drug survival and immunogenicity of certain anti-tumor necrosis factors seem to be better when used in combination with methotrexate. This report reviews the available evidence on the efficacy and effectiveness of methotrexate in psoriatic arthritis and its role in treating psoriatic arthritis to target, as well as in combination with biologic agents. Ideally, randomized placebo-controlled clinical trials evaluating methotrexate (using subcutaneous route of delivery) would provide much-needed clarity on the role of methotrexate in the management of psoriatic arthritis; however, issues around using a placebo in patients with active psoriatic arthritis may render such a trial unfeasible.
甲氨蝶呤在治疗类风湿关节炎和银屑病方面安全有效，因此尽管随机对照试验缺乏其在银屑病关节炎中疗效的证据，但已被用于治疗银屑病关节炎。尽管迄今为止最大的随机试验不支持将其作为一种疾病修饰疗法使用，但观察性研究支持其作用，并且当前的治疗建议批准将其作为治疗以周围关节炎为主的银屑病关节炎的一线药物。第一项针对银屑病关节炎的达标治疗研究，将严格控制与标准护理进行了比较，结果表明甲氨蝶呤作为单一疗法在最初 12 周内具有疗效。该试验显示了甲氨蝶呤的有效性，在 12 周的时间内改善了周围关节炎、皮肤和指甲疾病、附着点炎和指（趾）炎。关于联合（同时使用甲氨蝶呤和抗肿瘤坏死因子）治疗的作用，存在相互矛盾的证据。然而，当与甲氨蝶呤联合使用时，某些抗肿瘤坏死因子的药物存活率和免疫原性似乎更好。本报告回顾了甲氨蝶呤在银屑病关节炎中的疗效和有效性及其在达标治疗以及与生物制剂联合治疗中的作用的现有证据。理想情况下，评估甲氨蝶呤（使用皮下给药途径）的随机安慰剂对照临床试验将为甲氨蝶呤在银屑病关节炎管理中的作用提供急需的明确性；然而，在患有活动性银屑病关节炎的患者中使用安慰剂可能会使此类试验变得不可行。
