Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies

Asres Berhan

doi:10.1186/1471-2474-14-332

Abstract

BackgroundThis meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs).MethodsElectronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I2 statistics.ResultsThe odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.ConclusionsTofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

Highlights

This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs)
Inclusion criteria and study selection The predetermined study inclusion criteria for this metaanalysis were: 1) double- blind randomized clinical trial that assessed the efficacy and safety of tofacitinib as monotherapy or in combination with methotrexate in patients with rheumatoid arthritis who were on at least one of the nonbiologic or biologic DMARDs; 2) studies that recruited patients with rheumatoid arthritis that had been diagnosed for ≥ 6 months and had active disease on the basis of the American College of Rheumatology 1987 revised criteria [14]
In all the included studies concomitant medication with stable doses of low-dose corticosteroids (≤10 mg per day prednisone or equivalent), nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors were allowed for all treatment groups

Summary

Introduction

This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs). Of the non biologic DMARDs methotrexate is the most widely used [3,4]. Patients with an inadequate response to methotrexate are usually treated with biologic DMARDs such as tumor necrosis factor (TNF) inhibitors, either as monotherapy or in combination with nonbiologics DMARDs [2]. About 20-30% of the patients who were treated with biologic DMARDs monotherapy or in combination with nonbiologic DMARDs may not meet the ACR 20 improvement criteria (ACR20) [5,6,7]. Some other patients discontinue medication due to adverse events

Methods

Results

Conclusion