title: Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.
abstract: Tofacitinib is an oral JAK inhibitor that is used for the treatment of rheumatoid arthritis (RA). In previous clinical trials of tofacitinib, a Disease Activity Score in 28 joints (DAS28)-based analysis was used to assess outcomes. In this study, remission rates according to various remission criteria were evaluated across 5 phase III randomized controlled studies.
  
  
  
  In all 5 studies, tofacitinib was administered at a dosage of 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs. One of the studies included adalimumab 40 mg once every 2 weeks. In addition to the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]), a primary efficacy variable used in the phase III studies, disease activity was assessed post hoc by the 4-variable DAS28 using the C-reactive protein level (DAS28-4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean-based assessment.
  
  
  
  A total of 3,306 patients were analyzed (1,213 of these patients received tofacitinib 5 mg twice daily, 1,212 received tofacitinib 10 mg twice daily, 679 received placebo, and 202 received adalimumab 40 mg every 2 weeks). Remission rates varied according to the criteria used, with higher rates in the active-treatment groups for the DAS28-4(CRP) than for other scores. At month 3, remission rates with tofacitinib 5 mg twice daily were 18-22% using the DAS28-4(CRP), 5-10% using the DAS28-4(ESR), 4-7% using the SDAI, 5-6% using the CDAI, and 2-7% using the Boolean-based method. In contrast, the remission rates with placebo varied from 0% to 7%, with small differences between the DAS28-4(ESR) and the DAS28-4(CRP).
  
  
  
  Although tofacitinib at dosages of 5 mg twice daily and 10 mg twice daily was effective compared with placebo in achieving disease remission, regardless of the disease activity measure, remission rates were substantially higher when the DAS28-4(CRP) was used. The presence or absence and type of acute-phase reactants in remission criteria were significant contributors to remission rates across treatment groups. This finding has important consequences for trial design and clinical practice.
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.affiliation: Pfizer, Inc., Groton, Connecticut.
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.affiliation: Pfizer, Inc., Groton, Connecticut.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.affiliation: Pfizer, Inc., Groton, Connecticut.
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.affiliation: Pfizer, Inc., Groton, Connecticut.
authors.forename: Charles
authors.initials: C
authors.lastname: Mebus
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib