title: Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies.
abstract: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies.
authors.affiliation: Metroplex Clinical Research Center, Dallas, Texas, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: Center for Rheumatology, Albany Medical College, Albany, New York, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Kremer
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gruben
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Kanik
authors.affiliation: Pfizer Inc., New York, New York, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Koncz
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Gene
authors.initials: G
authors.lastname: Wallenstein
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Bethanie
authors.initials: B
authors.lastname: Wilkinson
authors.affiliation: Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Keystone
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases
keywords: Phase 2; efficacy; rheumatoid arthritis; safety; tofacitinib