Background Tacrolimus (TAC) is an immunosuppressive macrolide that blocks T-cell activation by specifically inhibiting calcineurin; it is widely administered after organ transplantation. TAC was approved in Japan for the treatment of rheumatoid arthritis (RA) in 2005. The emergence of biological disease–modifying anti-rheumatic drugs (DMARDs) has made remission an achievable goal for RA treatment. However, in some patients, biological DMARDs fail to achieve adequate suppression of disease activity or the efficacy of biological DMARDs is reduced. Therapeutic options for such patients include dose increases of biological DMARDs, switching to other biological DMARDs, and add-on use or dose increase of conventional anti-rheumatic drugs. The usage of add-on TAC has been reported in some studies [1,2].
Objectives We report the results of post-marketing surveillance to evaluate the safety and efficacy of TAC add-on therapy with biological DMARDs in Japanese RA patients without an adequate response to biological DMARDs in a real clinical setting.
Methods The observation period of this study was 24 weeks. Six hundred twenty-four patients were included in the safety population and 566 patients were included in the efficacy population. An inadequate response to biological DMARDs was defined as meeting all of the following conditions: Simplified Disease Activity Index (SDAI) >3.3 when TAC was started; both tender joint count and swollen joint count were the same or increased compared to those at 4 to 8 weeks prior to TAC; and biological DMARDs were used for at least 8 weeks prior to TAC. Efficacy was mainly evaluated using the SDAI and EULAR (European League Against Rheumatism) response criteria. SDAI improvement was defined as SDAI ≤11.
Results Mean age was 61.9 years and mean disease duration was 10.5 years. The mean TAC dose was 1.3 mg during the observation period. Adverse drug reactions (ADRs) occurred in 94 patients and serious ADRs were observed in 11 patients. Infections occurred in 21 patients and serious infections were observed in 8 patients. SDAI remission rate was 16.5% at week 24, SDAI improvement rate was 62.7% at week 24, and the mean SDAI was decreased from 20.0 at baseline to 10.8 at week 24. Interestingly, 40 patients (33.6%) out of 119 patients with high disease activity at baseline achieved SDAI improvement at week 24. Based on EULAR response criteria, moderate to good response rate was 64.7% at week 24.
Conclusions TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese RA patients who do not achieve an adequate response to biological DMARDs in a real clinical setting.
Naniwa T, Watanabe M, Banno S, Maeda T. Adding low dose tacrolimus in rheumatoid arthritis patients with an inadequate response to tumor necrosis factor inhibitor therapies. Rheumatol Int. 2009;29(11):1287–1291.
Mori S. Additional use of tacrolimus after switching to tocilizumab therapy in patients with primary lack of efficacy of infliximab therapy for rheumatoid arthritis. Mod Rheumatol. 2012;22(6):947–950.
Disclosure of Interest T. Takeuchi Grant/research support from: Astellas Pharma Inc., AbbVie GK, Asahikasei Pharma Corp., Bristol–Myers K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Consultant for: AbbVie GK, Asahi Kasei Medical K.K., Astra Zeneca K.K., Bristol–Myers K.K., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Nipponkayaku Co., Ltd., Novartis Pharma K.K., Speakers bureau: AbbVie GK., Astellas Pharma Inc., Bristol–Myers K.K., Celtrion, Chugai Pharmaceutical Co., Ltd., Diaichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nipponkayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., UCB., K. Ishida Employee of: Astellas Pharma Inc., K. Shiraki Employee of: Astellas Pharma Inc., T. Yoshiyasu Employee of: Astellas Pharma Inc.