Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs—a multicenter, double-blind, parallel-group trial

Abstract

In this trial, we investigated the safety and efficacy of tacrolimus used in addition to standard antirheumatic drugs in patients with rheumatoid arthritis. Tacrolimus 3 mg or placebo was orally administered once daily for 52 weeks in a double-blind manner to patients with early active rheumatoid arthritis receiving other disease-modifying antirheumatic drugs (DMARDs). A total of 123 patients were randomized to the tacrolimus group (61 patients) and to the placebo group (62 patients). In the tacrolimus group, 70.5% achieved a clinical response according to American College of Rheumatology (ACR) 20 criteria, whereas 45.2% in the placebo group did so (P = 0.005). The tacrolimus group also showed significant improvement in terms of the European League Against Rheumatism (EULAR) response criteria of "good or moderate" versus the placebo group (86.9 vs. 56.5%, respectively). Likewise, significantly more patients in the tacrolimus group versus the placebo group achieved remission of the Disease Activity Score in 28 joints (DAS28) (45 vs. 21%). The mean changes in the Total Sharp Score and erosion score were lower in the tacrolimus group, but the differences between the two groups were not significant. There was no significant difference between the two groups in the incidence of adverse events. Based on these results, we can conclude that the additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to other DMARD treatments is useful, and this could become one of the treatment options for these rheumatoid arthritis patients.

Efficacy and safety of add‐on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate

“…Adverse events reported in our study were consistent with side effects of both tacrolimus and leflunomide reported in the literature . Cases of gastrointestinal disorders including dyspepsia or diarrhea were slightly higher in the tacrolimus plus MTX group (Table ).…”

“…We did not witness any warning signal of deteriorating renal function in our patients during the 24‐week study. A 52‐week, placebo‐controlled trial of add‐on tacrolimus in early RA patients who had inadequate response to other cDMARDs showed ACR20 response of 70.5% at the end the study (DAS28 remission in 45%) compared with 45.2% in the placebo group . Our DAS28 remission rate at 24 weeks in the tacrolimus plus MTX group was 48.7% in the FA set and 57.1% in the PP set.…”

Long‐term efficacy and safety of add‐on tacrolimus for persistent, active rheumatoid arthritis despite treatment with methotrexate and tumor necrosis factor inhibitors

“…As for radiographic efficacy, several observational studies have demonstrated tacrolimus has the potential to inhibit progression of joint damage in RA . A double‐blind, placebo‐controlled trial to investigate the clinical and radiographic efficacy of adding tacrolimus in patients with active RA despite treatment with conventional synthetic DMARDs, mostly methotrexate, demonstrated no significant difference in radiographic progression between the tacrolimus group and the placebo group . However, subgroup analysis of this study revealed tacrolimus prevented structural damages in patients with a baseline CRP level less than 1.5 mg/dL …”

Inhibitory effect of tacrolimus on progression of joint damage in patients with rheumatoid arthritis

“…A recent double‐blind parallel‐group trial of tacrolimus in patients with early RA showed a significantly improved response and increased remission rate by additional use of tacrolimus . However, after 52 weeks, changes in mTSS were not significantly different between the tacrolimus and placebo groups.…”