Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population

Stephen Hall; Peter Nash; Maureen Rischmueller; David Bossingham; Paul Bird; Nicola Cook; David Witcombe; Koshika Soma; Kenneth Kwok; Krishan Thirunavukkarasu

doi:10.1007/s40744-018-0118-2

Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population

Rheumatol Ther. 2018 Dec;5(2):383-401. doi: 10.1007/s40744-018-0118-2. Epub 2018 Jun 11.

Authors

Affiliations

¹ Department of Medicine, Cabrini Health and Monash University, Emeritus Research, Melbourne, Australia.
² Department of Medicine, University of Queensland, Brisbane, Australia.
³ Department of Rheumatology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia.
⁴ Cairns Clinical School, James Cook University, College of Medicine and Dentistry, Cairns, Australia.
⁵ Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁶ Department of Rheumatology, Royal Perth Hospital, Perth, Australia.
⁷ Immunology and Inflammation, Pfizer Australia, Sydney, Australia. david.witcombe@pfizer.com.
⁸ Clinical Research, Pfizer Inc, Groton, CT, USA.
⁹ Biostatistics, Pfizer Inc, New York, NY, USA.
¹⁰ Immunology and Inflammation, Pfizer Australia, Sydney, Australia.

Abstract

Introduction: In Australia, there is an unmet need for improved treatments for rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. To provide an overview of key study outcomes for tofacitinib in Australian patients, we analyzed the efficacy and safety of tofacitinib in the Australian subpopulation of global RA phase III and long-term extension (LTE) studies.

Methods: Data were pooled from the Australian subpopulation of four phase III studies and one LTE study (database not locked at cut-off date: January 2016). Patients in the phase III studies received tofacitinib 5 or 10 mg twice daily (BID), placebo (advancing to tofacitinib at months 3 or 6), or adalimumab, with background methotrexate or conventional synthetic disease-modifying antirheumatic drugs. Patients in the LTE study received tofacitinib 5 or 10 mg BID. Efficacy endpoints were American College of Rheumatology (ACR) 20/50/70 response rates, and change from baseline in the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Safety endpoints included incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs. AEs of special interest and laboratory parameters were analyzed in the LTE study.

Results: Across phase III studies (N = 100), ACR response rates and improvements in DAS28-4(ESR) and HAQ-DI scores were numerically greater with tofacitinib vs. placebo at month 3, and increased until month 12. The results were sustained in the LTE study (N = 99) after 60 months' observation. In general, the efficacy and safety profiles of tofacitinib were similar to those of the global RA population.

Conclusions: In Australian patients with RA, tofacitinib therapy demonstrated sustained efficacy and consistent safety over ≥ 60 months' treatment.

Funding: Pfizer Inc. TRIAL REGISTRATION NUMBERS (ALL CLINICALTRIALS.GOV): NCT00960440; NCT00847613; NCT00856544; NCT00853385; NCT00413699.

Keywords: Australia; Efficacy; Rheumatoid arthritis; Safety; Tofacitinib.

Associated data

ClinicalTrials.gov/NCT00853385
ClinicalTrials.gov/NCT00960440
ClinicalTrials.gov/NCT00847613
ClinicalTrials.gov/NCT00856544
ClinicalTrials.gov/NCT00413699