Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis: a possible alternative treatment to methotrexate?

Tacrolimus (Tac) is a T‐cell‐specific calcineurin inhibitor that prevents activation of helper T cells, thereby inhibiting transcription of the early activation genes of IL‐2, and suppressing the production of TNF‐a, IL‐1b and IL‐6. Considering its effects, Tac is expected to have clinical benefits in the treatment of patients with active rheumatic diseases. Indeed, to date, several papers have described the efficacy and safety of Tac treatment for patients with rheuma‐ toid arthritis (RA) [1–5], lupus nephritis [6,7] and systemic‐onset juvenile idiopathic arthritis [8]. In the paper being evaluated, the authors have attempted to demonstrate the efficacy and safety of Tac treatment in patients with active RA in a hospital‐based prospective observational setting [1]. On the basis of the result of the study, the authors appear to provide further useful infor‐ mation regarding Tac treatment for treating physicians. The authors have used information drawn from a database (the IORRA database) of the authors’ academic center (The Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan), which was established in October 2000. Using this database, data sets of patient clinical variables before and after Tac treatment were collected from a prospective obser‐ vational cohort of patients with active RA. Thus, most of the information appears to pertain to ordinary Japanese RA patients in a clinical setting. A total of 7512 patients were registered in the database, in which patients selection bias appears to be very small. Of these patients, 101 consecu‐ tive patients with active and disease‐modifying antirheumatic drug (DMARD)‐resistant RA were treated with Tac using an initial average dose of 1.62 mg/day. Clinical and laboratory assessments were performed at baseline, month 4 and month 12. The study was conducted in accordance with the following: a hospital‐based prospective observational study using last obser‐ vation carried forward methodology; and the variables included the European League Against Rheumatism improvement criteria using the Disease Activity Score (DAS)28 scale and the American College of Rheumatology prelimi‐ nary criteria for improvement (ACR20). The results were compared with 5867 patients with RA from the 13th phase of the IORRA cohort (from October 2006 in the database). When compared with the IORRA database as the control group, the Tac‐treated patients were of a similar average age (62 years old) and had a similar disease duration (13 years). However, these patients had received higher doses of methotrexate (MTX; 8.59 mg/week) and pred‐ nisolone (6.92 mg/day), and had used nonster‐ oidal anti‐inflammatory drugs more frequently, indicating that Tac was preferentially prescribed to RA patients with higher disease activity [1]. Comorbidities (i.e., respiratory disease, hyper‐ lipidemia and Type 2 diabetes mellitus) were frequently observed in 26 patients (25.7%) of the Tac‐treated group at baseline. Thus, the average daily dose of Tac at entry was relatively low at 1.62 mg/day, which resulted in an aver‐ age whole blood Tac concentration of 4.3 ng/ml approximately 12 h post‐dosing. Evaluation of: Kitahama M, Okamoto H, Koseki Y et al.: Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis. Mod. Rheumatol. DOI: 10.1007/s10165–010–0319–1 (2010) (Epub ahead of print). Although the use of biologic agents combined with methotrexate has been reported to be effective in the treatment of patients with rheumatoid arthritis, a proportion of rheumatoid arthritis patients do not experience disease remission, partly because of their complications or background factors. In this context, tacrolimus treatment might be effective and safe for such patients. In the study being evaluated, the authors provide additional useful information for treating physicians. However, further studies regarding the long-term efficacy and safety of tacrolimus treatment in a larger number of active rheumatoid arthritis patients are necessary in order to draw valid conclusions.