Prevention of joint destruction by tacrolimus in patients with early rheumatoid arthritis: a post hoc analysis of a double-blind, randomized, placebo-controlled study

Abstract

Objectives A multicenter, randomized, double-blind, placebo-controlled study of the oral calcineurin inhibitor tacrolimus was performed in patients with early rheumatoid arthritis who had responded poorly to disease-modifying antirheumatic drugs (DMARDs), and factors related to suppression of joint destruction were investigated.

Methods The change in the total Sharp score (∆TSS) was assessed by univariate analysis in patients with X-ray films to identify the main determinant of a ∆TSS of <0.5 in week 52. Patients with this factor were then investigated further.

Results Univariate analysis showed that a baseline C-reactive protein (CRP) level of <1.5 mg/dL was the major determinant of ∆TSS <0.5 at week 52 in the tacrolimus group. Detailed analysis of patients with a baseline CRP of <1.5 mg/dL revealed no significant differences in background factors between the two groups. In week 52, ∆TSS was significantly smaller in the tacrolimus group than in the placebo group (2.67 ± 5.40 vs. 8.05 ± 10.32, respectively, p = 0.017). Both groups had a similar incidence of adverse reactions.

Conclusions Adding tacrolimus to DMARDs significantly suppressed disease activity and joint destruction in patients with early rheumatoid arthritis, a disease duration ≤3 years, a CRP <1.5 mg/dL, and a poor response to oral DMARDs.

Keywords::

• DMARD
• Rheumatoid arthritis
• Tacrolimus

Acknowledgments

The authors thank Astellas Pharma Inc., which sponsored the study and provided editorial support. Statistical analysis was also performed by Astellas Pharma Inc. under the supervision of the authors.

Conflict of interest

Y. Tanaka, S. Kawai, T. Takeuchi, K. Yamamoto, and N. Miyasaka have received consulting fees from Astellas Pharma Inc.