Efficacy of doxycycline as a combination therapy in the treatment of rheumatoid arthritis: a randomized controlled clinical trial

Abstract
Background
This single-center randomized open-label clinical trial evaluates the effectiveness of doxycycline as a combination therapy for active rheumatoid arthritis (RA) with methotrexate (MTX).

Materials and methods
One hundred and sixty RA patients were recruited who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Subjects were randomly allocated in a 1:1 ratio into one of two treatment arms; one group was maintained on MTX alone and the other group on MTX together with doxycycline orally 200 mg daily. Follow-up clinical response, erythrocyte sedimentation rate (ESR), levels of C-reactive protein (CRP), and disease activity score 28 (DAS28-CRP) after 3 months were done.

Results
There was a significant difference regarding DAS28-CRP between the two groups (median (IQR) 4.26 (3.6–5) for those treated with MTX alone compared with 2.8 (2.37–3.5) for those treated with MTX together with doxycycline) (p = 0.005). A higher number of patients treated with doxycycline in combination with MTX achieved remission (40.5%) compared to patients who received MTX alone (13.5%). The levels of ESR and CRP were lower in patients treated with MTX and doxycycline and this was statistically significant (p = 0.005, p = 0.003 respectively).

Conclusion
Doxycycline as a cost-effective combination therapy with MTX can achieve higher rates of remission than MTX alone in RA patients without causing increase in the adverse events profile.

Trial registration
Clinical Trials.gov, NCT03194204. Registered on 21 June 2017