Background The advancement in biological agents and improvement in treatment strategy enabled many patients with rheumatoid arthritis to achieve remission or low disease activity. On the other hand, the cost of biological agents has become major problem in health economics and for some patients biological therapy is not affordable. Therefore recently, combination of conventional disease-modifying anti-rheumatic drugs (DMARDs) therapy have been reconsidered and some studies proved that triple therapies could be as efficacious as biologic agents.
Objectives To compare retrospectively the triple therapy consisting of methotrexate (MTX), tacrolimus (TAC) and Mizoribine (MZR) with biologic agents in patients with established rheumatoid arthritis with no improvement despite the treatment with MTX.
Methods Fifty one established RA patients with a disease duration more than 2 years were included. They showed no improvement the despite treatment with MTX for at least 3 months. We classified patients in 2 groups, one group with the addition of TAC and MZR (csD group) and the other with TNF inhibitor (bD group). There were no significant differences between the backgrounds of the two groups. We evaluated DAS28CRP scores, the van der Heijde-modified total sharp scores  and ARASHI change scores  which is a scoring system of large joint destruction and compared them between both groups for 2 years. Moreover we performed questionnaire of patient's satisfaction for the therapies.
Results There were no significant differences of DAS28CRP at baseline. Both groups had significant improvement of the scores at final evaluation. There was a significant difference of the improvement rate in DAS28CRP of the bD group in comparison with the csD group at 1 month after treatment. However, no significant difference was observed between the two groups at 3 months and beyond after the treatment (Figure). There was a significant difference in the radiographic progression of small joints between both groups at the final evaluation (csD 0.53/year and bD 0.19/year). Main reasons for the discontinuation the treatment was the adverse events in csD group (csD 23.1% and bD 6.9%), as opposed to patient's intension in bD group. Although patient's satisfaction for improvement of disease activity was simila between the two groups, patient's intension to continue the therapy in csD group was higher than in the bD group. Many patients in bD group complained of the treatment expense.
Conclusions Triple therapy using TAC, MZR and MTX enabled good clinical benefit even in comparison with the biologic agents. Moreover the triple therapy showed rapid effect which was significant within 3 months. However we should also focus on the mechanism for inferior effect on preventing the small joint destruction.
van der Heijde D, et al. J Rheumatol. 2000;27:261–3
Kaneko A, et al. Mod Rheumatol. 2013;23:1053–1062
Disclosure of Interest None declared