title: Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis.
abstract: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi).
  
  
  
  A systematic literature review identified 5 randomized placebo-controlled trials that evaluated tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) against placebo in patient populations with RA with a prior IR to TNFi. The definition of TNFi-IR varied across studies, and included patients with an IR or who had failed treatment with TNFi for any reason. A network meta-analysis was conducted comparing study data with regard to American College of Rheumatology response rates and Health Assessment Questionnaire-Disability Index improvement at weeks 12 and 24, rates of treatment withdrawal due to all causes; adverse events (AEs) and lack of efficacy; and rates of AEs, serious AEs, and serious infections.
  
  
  
  The 5 trials included a total of 2136 patients. Tofacitinib 5 mg twice daily combined with methotrexate was found to have relative risk estimates of American College of Rheumatology responses and change from baseline in Health Assessment Questionnaire-Disability Index score comparable with abatacept, golimumab, rituximab, and tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs. Withdrawal rates from trials due to all causes and AEs were comparable between treatments, and tofacitinib had a lower rate of withdrawals due to lack of efficacy. Rates of AEs and HAQ-DI were comparable between tofacitinib, other active treatments, and placebo. No serious infections were reported with tofacitinib during the placebo-controlled period (up to week 12) in this study population; rates of serious infection with other active treatments were generally low and similar to placebo.
  
  
  
  During a 24-week period, tofacitinib had efficacy and rates of AEs comparable with currently available bDMARDs in the treatment of patients with RA who had a prior IR to TNFi. ClinicalTrials.gov identifiers: ORAL Step, NCT00960440; ATTAIN, NCT00124982; GO-AFTER, NCT00299546; RADIATE, NCT00106522; REFLEX, NCT00462345.
authors.affiliation: Mapi, Boston, Massachusetts.
authors.forename: Maria-Cecilia
authors.initials: MC
authors.lastname: Vieira
authors.affiliation: Pfizer Inc, Groton, Connecticut.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Jansen
authors.affiliation: Mapi, Boston, Massachusetts.
authors.forename: Brielan
authors.initials: B
authors.lastname: Smiechowski
authors.affiliation: Pfizer Inc, Tadworth, Surrey, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Spurden
authors.affiliation: Pfizer Inc, Groton, Connecticut. Electronic address: gene.wallenstein@pfizer.com.
authors.forename: Gene V
authors.initials: GV
authors.lastname: Wallenstein
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000069283:Rituximab / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept; C479163:tofacitinib; C529000:golimumab; C502936:tocilizumab; D008727:Methotrexate
keywords: disease-modifying antirheumatic drugs; rheumatoid arthritis; tofacitinib; tumor necrosis factor inhibitors