Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: A double‐blind trial

Abstract

Objective. To evaluate the efficacy and safety of tacrolimus as monotherapy in controlling the signs and symptoms of patients with rheumatoid arthritis (RA).Methods. This was a 6-month, phase III, doubleblind, multicenter study. Patients with active RA who had discontinued all disease-modifying antirheumatic drugs (DMARDs) for an appropriate washout period (at least 1 month) and who, after the washout period, had a stable joint count (at least 10 tender/painful joints and 7 swollen joints) were stratified according to DMARD intolerance or DMARD resistance, and randomized to receive a single daily oral dose of placebo, tacrolimus 2 mg, or tacrolimus 3 mg.Results. A total of 464 patients received at least 1 dose of study drug. Baseline characteristics were similar among the 3 treatment groups. American College of Rheumatology 20% improvement (ACR20) success (defined as completion of 6 months of treatment and an ACR20 response at the month 6 visit) for the placebo, tacrolimus 2 mg, and tacrolimus 3 mg groups was 10.2%, 18.8% (P < 0.05 versus placebo), and 26.8% (P < 0.0005 versus placebo), respectively. At the end of treatment, the ACR20 and ACR50 response rates in the 3-mg group were 32.0% (P < 0.005 versus placebo) and 11.8% (P < 0.05 versus placebo), respectively. DMARDintolerant patients had better ACR response rates than did DMARD-resistant patients. Although serum creatinine levels increased by >40% from baseline at some time during the trial in 20% and 29% of patients receiving tacrolimus 2 mg/day and 3 mg/day, respectively, the serum creatinine level remained within the normal range throughout the trial in ϳ90% of patients.Conclusion. Tacrolimus, at dosages of both 2 mg/day and 3 mg/day, is efficacious and safe as monotherapy for patients with active RA, but treatment with the 3-mg dose of tacrolimus resulted in generally better ACR response rates.Rheumatoid arthritis (RA) is a chronic autoimmune disorder that requires early diagnosis and aggressive treatment to minimize the morbidity associated with its progression (1,2). Disease-modifying antirheumatic drugs (DMARDs) and biologic modifiers have been used to accomplish these objectives (3-23). A common prominent feature of these agents is their immunosuppressive properties.Tacrolimus (Prograf, FK506), an orally available macrolide calcineurin inhibitor, is an immunomodulatory and antiinflammatory agent (24-31). It diminishes the ability of calcineurin to dephosphorylate and translocate the nuclear factor of activated T cells that initiates gene transcription for the synthesis of inflammatory cytokines such as tumor necrosis factor ␣, interleukin-2,

Effect of Additional Administration of Tacrolimus in Patients With Rheumatoid Arthritis Treated With Biologics

“…Tac also suppresses the production of cytokines such as IL -2 and TNFα 11,12) . The usefulness of Tac for RA has been demonstrated in double -blind, placebo -controlled, parallel -group studies and controlled studies compared with other drugs 13,14) . Tac up to 3 mg/daily is approved to be used for the patients with RA in Japan.…”

Tacrolimus, a Calcineurin Inhibitor, Overcomes Treatment Unresponsiveness Mediated by P-glycoprotein on Lymphocytes in Refractory Rheumatoid Arthritis

“…The response of patients with RA to tacrolimus treatment is normally investigated about 1-2 months after initiation of such treatment [19][20][21][22][23][24][25] . In our study, however, we noted that some patients responded …”

“…Studies indicate that the clinical effects of tacrolimus on RA appear after 1-2 months of treatment [19][20][21][22][23][24][25] . In our study, we report rapid improvement in clinical symptoms and laboratory tests after 2-week treatment with tacrolimus.…”

Treatment of refractory juvenile dermatomyositis with tacrolimus

“…It is widely used in transplant medicine and has been shown to be effective in several autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease [3][4][5]. Beneficial effects of tacrolimus have also been demonstrated in adult polymyositis and dermatomyositis [6][7][8][9][10].…”