Methotrexate in Patients with Hand Erosive Osteoarthritis Refractory to Usual Treatments: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Objectives: No studies have assessed the effect of methotrexate (MTX) in osteoarthritis of the hand (HOA). The purpose of our study was to examine the effect of MTX on pain and structural progression in symptomatic erosive HOA (EHOA). Methods: This 1-year prospective, monocentric, randomized, double-blind, placebo-controlled study followed patients with symptomatic EHOA. Patients were randomized into two groups: 10 mg MTX per week or placebo. The primary endpoint was pain assessment at 3 months, and the secondary endpoints were clinical features (visual analogue scale pain), radiographic features (anatomical radiographic score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months. This study was reported on www.ClinicalTrial.gov (NCT1968405). Results: Sixty-four patients with HOA were randomized to either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in VAS pain score (mm) (MTX: 17.5 (28.4) vs placebo: 8.4 (25.2); p=0.2). Erosive joints progressed significantly more to a remodeling phase in MTX group than in placebo group (27% vs 15%; p=0.03). Joints with joint space loss appeared to be less eroding in MTX group than in placebo group (8% vs 29%; p=0.2). The level of IL6 (p<0.0001) and presence of synovitis on MRI (p=0.02) at baseline were found to be predictive factors for erosive structural evolution of non-erosive joints. Conclusion: MTX did not effectively relieve pain after 3 months in EHOA. However, MTX significantly impact the progression of joint damage compared to placebo. The presence of systemic and local inflammation at baseline as a predictor of erosive progression found in our study may explain the structural results. Trial Registration: This study was reported on www.ClinicalTrial.gov (NCT 01068405). Funding Statement: The authors stated: There was no external funding. Declaration of Interests: The authors stated: None declared. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Nice University Hospital Center. All patients provided written informed consent. The study was conducted in accordance with the principles of the Helsinki Declaration.