title: Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs.
abstract: BACKGROUND
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis.
  
  
  METHODS
  In this 6-month, phase 3, randomized, placebo-controlled trial, 611 patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR) were randomized 4:4:1:1 to receive: tofacitinib 5 mg BID or tofacitinib 10 mg BID for the duration of the study, or placebo for 3 months followed by tofacitinib 5 mg BID or tofacitinib 10 mg BID. Patient-reported outcomes (PROs) included: Patient Global Assessment of Disease Activity (PtGA); Patient Assessment of Pain (Pain); Health Assessment Questionnaire-Disability Index (HAQ-DI); Medical Outcomes Survey (MOS) Short Form-36 (SF-36); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); and MOS Sleep Scale. Time-to-event data (PtGA and Pain) were collected using an interactive voice response system daily diary (baseline through day 14).
  
  
  RESULTS
  At month 3, tofacitinib 5 and 10 mg BID demonstrated statistically significant improvements versus placebo in PtGA (both p < 0.0001), Pain (both p < 0.0001), HAQ-DI (both p < 0.0001), SF-36 Physical (p < 0.0001) and Mental (p < 0.05 [5 mg BID] and p < 0.0001 [10 mg BID]), Component Summary scores and all domain scores (p < 0.05-p < 0.0001) and FACIT-F (both p < 0.0001). Statistically significant changes from baseline in MOS Sleep Scale were reported for 10 mg BID (p < 0.05). Benefits of tofacitinib treatment were rapid in onset and significant improvements were reported at week 2 for PtGA, Pain and HAQ-DI, and differentiation from baseline was seen as early as 3 days after treatment initiation for interactive voice response system (IVRS) PtGA and IVRS Pain. The numbers needed to treat for patients to report changes greater than or equal to the minimum clinically important difference in PtGA, Pain, HAQ-DI, SF-36 Physical Component Summary score and FACIT-F ranged between 4.0-6.1 (5 mg BID) and 3.2-5.0 (10 mg BID).
  
  
  CONCLUSIONS
  Tofacitinib monotherapy in DMARD-IR patients resulted in statistically significant and clinically meaningful improvements in multiple PROs versus placebo at month 3, with sustained improvements over 6 months.
  
  
  BACKGROUND
  Clinicaltrials.gov registration NCT00814307 , registered 22 December 2008.
authors.affiliation: Biopharmaceutical Consultant, Portola Valley, CA, USA. vstrand@aol.com.|Stanford University, Palo Alto, CA, USA. vstrand@aol.com.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.affiliation: Center for Rheumatology, Albany Medical College, Albany, NY, USA. jkremer@joint-docs.com.
authors.forename: Joel
authors.initials: J
authors.lastname: Kremer
authors.affiliation: Pfizer Inc, 445 Eastern Point Road, MS 8260-2515, Groton, CT, 06340, USA. Gene.wallenstein@pfizer.com.
authors.forename: Gene
authors.initials: G
authors.lastname: Wallenstein
authors.affiliation: Pfizer Inc, 445 Eastern Point Road, MS 8260-2515, Groton, CT, 06340, USA. keith.s.kanik@pfizer.com.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kanik
authors.affiliation: Pfizer Inc, 445 Eastern Point Road, MS 8260-2515, Groton, CT, 06340, USA. carol.a.connell@pfizer.com.
authors.forename: Carol
authors.initials: C
authors.lastname: Connell
authors.affiliation: Pfizer Inc, 445 Eastern Point Road, MS 8260-2515, Groton, CT, 06340, USA. david.gruben@pfizer.com.
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.affiliation: Pfizer Inc, 445 Eastern Point Road, MS 8260-2515, Groton, CT, 06340, USA. samuel.h.zwillich@pfizer.com.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX, USA. rfleischmann@arthdocs.com.
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D011788:Quality of Life; D057566:Self Report; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib