Background Tacrolimus (TAC), a calcineurin inhibitor, is used in the treatment of rheumatoid arthritis (RA) in Japan. Efficacy of TAC has been reported in several studies [1, 2]. TAC is prescribed as monotherapy or with DMARDs including biological agents in Japanese clinical setting. It is unclear which prescribing pattern is most effective among the use of TAC.
Objectives The objective of this retrospective study is to compare the efficacy of TAC among different prescribing patterns in RA patients.
Methods 107 RA patients (85 female and 22 male) treated with TAC as monotherapy or with other DMARDs in our institute were included in this study. These patients were divided into three groups. Patients treated with TAC monotherapy were called MG (40 cases). Patients treated with TAC which was added onto non-biological DMARDs including methotrexate (MTX) and sulfasalazine (SSZ) were called CG (48 cases). Patients treated with TAC which was added onto biological DMARDs were called BG (19 cases). Baseline point was when TAC was initiated and the efficacy was evaluated until one year after initiation of TAC. Disease activity score 28 using erythrocyte sedimentation rate (DAS28), serum C-reactive protein level (CRP) and modified health assessment questionnaire (mHAQ) were uses to evaluate the efficacy of TAC.
Results Mean age (years old) at baseline in MG, CG and BG were 71, 63 and 58, respectively. Mean RA duration (years) at baseline in MG, CG and BG were 18.8, 14.9 and 11.3, respectively. RA patents in MG were old and had long RA duration compared with CG and BG. 40% and 31% in concomitant DMARDs in CG were MTX and SSZ, respectively. 60%, 35% and 5% in concomitant biological agents in BG were etanercept, infliximab and adalimumab, respectively. Baseline values in DAS28 were 5.50, 5.33 and 6.10 in MG, CG and BG, respectively. Baseline values in CRP (mg/dl) were 3.86, 3.63 and 4.76 in MG, CG and BG, respectively. Baseline values in mHAQ were 1.277, 0.853 and 1.328 in MG, CG and BG, respectively.Mean improvement values (MIV) for one year in DAS28 were 0.67±1.51, 0.73±1.29 and 1.21±0.91 in MG, CG and BG, respectively (not significant). MIV for one year in CRP were 1.46±3.19, 1.55±2.98 and 3.65±3.12 in MG, CG and BG, respectively (significant between MG and BG). MIV for one year in mHAQ were 0.159±0.462, 0.052±0.344 and 0.148±0.330 in MG, CG and BG, respectively (not significant).
Conclusions There were the differences in the characteristics of patients among three groups. The efficacy of TAC in BG was the best among three groups. The factors influencing the results of this study might be the TAC’s inhibitory effects on drug exclusion function of P-glycoprotein  and the TAC’s inhibitory effects on production of anti-antibody antibody which inhibited the effects of biological agents in addition to the differences in patients’ characteristics.
Morita Y et al. Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in Japan: a retrospective study. Mod Rheumatol. 2008; 18: 379-384.
Kitahara M et al. Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis. Mod Rheumatol. 2010; 20: 478-485.
Suzuki K et al. Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis. J Rheumatol. 2010; 3: 512-520.
Disclosure of Interest None Declared