The effects of methotrexate and hydroxychloroquine combination therapy vs methotrexate monotherapy in early rheumatoid arthritis patients.

Objectives: To investigate the added value of MTX-HCQ combination therapy (CTG) in early RA in a controlled cohort study. MTX monotherapy (MTG) is recommended as (part of) first choice treatment but no head-to-head comparisons are available comparing MTX-HCQ CTG with MTG.

Methods: RA patients from the Sint Maartenskliniek and Radboudumc Nijmegen who started MTX with or without concomitant HCQ from April 2010 to October 2015 were included. The primary outcome was the between-group ΔDAS28-CRP at 6 months, and secondary outcomes were ΔDAS28-CRP at 12 months, EULAR response at 6 and 12 months, and treatment intensification. Regression modelling was used to correct for confounding.

Results: We included 325 patients, with only small between-group differences at baseline. The DAS28-CRP improvement at 6 months was larger in the CTG (Δ = 0.38 (CI: 0.01, 0.76)), and the difference between groups in DAS28-CRP improvement was smaller at 12 months (Δ = 0.22 points (CI:-0.19, -0.62)). At 6 months, a higher percentage of patients had a good EULAR response in the CTG (Δ = 15% (CI: 2.7%, 27%)). This difference was reduced at 12 months (Δ = 6% (CI -6.4%, 19%)). Treatment intensification with conventional synthetic DMARDs was more likely in the MTG (Δ = 31% (CI: -43%, 19%)). The proportion of patients starting biologic DMARD treatment during the observation period was comparable (Δ = 2% (CI: -8%, 12%)).

Discussion: In contrast to indirect comparison review data, MTX-HCQ seems somewhat more effective after 6 months than MTX monotherapy in early RA patients. After 12 months, we observed no significant differences between the two strategies, probably due to treat-to-target efforts.