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

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.

Figures

Fig. 1

Efficacy over time in the pooled phase III study population, as measured by a ACR20 response rates, b ACR50 response rates, c ACR70 response rates, d proportion of patients achieving clinical remission and LDA at month 12, as measured by DAS28-4(ESR), e mean change from baseline in DAS28-4(ESR), and f mean change from baseline in HAQ-DI (FAS, no imputation). Remission was defined as DAS28-4(ESR) < 2.6. LDA was defined as DAS28-4(ESR) ≤ 3.2. ACR American College of Rheumatology, BID twice daily, DAS28-4(ESR) Disease Activity Score in 28 joints, erythrocyte sedimentation rate, FAS full analysis set, HAQ-DI Health Assessment Questionnaire-Disability Index, LDA low disease activity, Q2W every other week, SE standard error

Fig. 2

PROs in the pooled phase III study population showing the mean changes from baseline a across eight SF-36 domain scores at month 3, b in SF-36 PCS to month 12, and c in SF-36 MCS to month 12 (FAS, no imputation). BID twice daily, FAS full analysis set, MCS mental component summary, PCS physical component summary, PROs patient-reported outcomes, Q2W every other week, SE standard error, SF-36 Short Form-36 Health Survey

Fig. 3

Summary of changes in laboratory variables following treatment with tofacitiniba during the LTE study, showing mean change from baseline in a hemoglobin (g/dl), b absolute lymphocyte count (109 cells/l), c absolute neutrophil count (109 cells/l), d serum creatinine (mg/dl), and e HDL and LDL cholesterol (percent change). BID twice daily, HDL high-density lipoprotein, LDL low-density lipoprotein, LTE long-term extension, SE standard error, TDD total daily dose