Background Tacrolimus is an immunosuppressive drug widely used for the prevention and treatment of allograft rejection in organ transplantation. In Japan it was approved of rheumatoid arthritis (RA) in 2005. Tacrolimus prevents differentiation and maturation of osteoclasts by inhibiting the activation of NFATc induced by RANKL in osteoclasts . Therefore, it is expected that tacrolimus directly suppress the activation of osteoclast as well as the production of cytokines related to RA inflammation. These effects of tacrolimus may achieve the inhibition of joint destruction. Recently, an excellent clinical response of tacrolimus has been demonstrated in RA patients that were resistant to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). However, its inhibitory effect on the joint destruction remains to be clarified.
Objectives The aim of this study is to examine the inhibitory effect of tacrolimus on the progression of joint damage in patients with RA.
Methods We have retrospectively examined 27 patients with RA that failed to respond to non-biologic DMARDs and administered tacrolimus for one year or more with periodical X-ray examination of both hands and feet. Expert readers analyzed the photographs and recorded modified total Sharp scores (mTSS). Progression of joint destruction was evaluated with an estimated yearly change in mTSS (ΔmTSS). Disease activity was assessed with DAS28-ESR. Treatment responses were determined by using EULAR response criteria
Results The mean age was 68.2±10.5 years old, and the duration of RA was 12.5±8.5 years. The mean DAS28-ESR in the patients was 4.99 at baseline and gradually improved to 3.65 at one year. Good and moderate response rate according to EULAR improvement criteria was 22.2% and 59.3% at one year, respectively. The mean ΔmTSS before tacrolimus administration was 11.1. Mean ΔmTSS then decreased to a value of 2.98 one year after tacrolimus treatment, indicating the inhibition of the progression of joint damage. We also examined the effect of tacrolimus on the radiographic joint damage at 2 years in 19 patients who were administered tacrolimus for two years or more. In these patients, ΔmTSS during the second year was significantly lower than that in the first year, although DAS28-ESR at two years was almost same as that at one year. Furthermore, the rate of patients with 0 or less ΔmTSS, indicating complete inhibition or repair of joint damage, significantly increased to 36.8% at two years, compared with 21.1% at one year.
Conclusions These findings suggest that tacrolimus has a potential to inhibit the progression of joint damage in RA patients.
Takayanagi H et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Developmental Cell 2002.
Disclosure of Interest None Declared
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