Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).
Objectives To assess the efficacy and safety of tofacitinib after temporary discontinuation and reinitiation of therapy in RA patients (pts).
Methods Data were collected from a randomised, parallel-group (grp), controlled, open label, vaccine sub-study in RA pts participating in a long-term extension (LTE) study (NCT00413699). Pts were ≥18 years of age with active RA and had received tofacitinib 10 mg BID for ≥3 months. The sub-study included 2 treatment (tx) grps: “continuous tx” (tofacitinib 10 mg twice daily [BID] as monotherapy or with methotrexate [MTX]) and “interrupted tx” (tofacitinib withdrawn for 2 weeks post-randomisation [Day 1–Day 15; Visits 1–3], then tofacitinib 10 mg BID reinitiated as monotherapy or with MTX at Visit 3); randomisation was stratified by MTX use. Pneumococcal and influenza vaccines were administered to all pts on Day 8 (Visit 2; vaccine titers reported previously1). Blood samples were taken on Days 8, 15 (Visit 3) and 43 (Visit 4). Efficacy endpoints included change from baseline in C-reactive protein (CRP), Health Assessment Questionnaire Disability Index (HAQ-DI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at each visit. A mixed-effects model with repeated measures was used to evaluate treatment effect at each visit. Analyses for efficacy were exploratory, with no multiplicity adjustment for comparisons.
Results Of the 199 pts in this analysis (continuous, n=100; interrupted, n=99), 117 received concomitant MTX. At LTE study baseline (BL) in the continuous and interrupted grps, respectively: 81.8/83.8% of pts were white, 84.8/86.9% were female and mean age was 55.0/53.9 years. BL (Day 1) values for CRP, HAQ-DI and DAS28-4(ESR) were generally similar between groups. At Day 8, mean CRP and DAS28-4(ESR) significantly increased from BL for interrupted vs continuous tx; HAQ-DI values were similar between grps (Figure). As expected at Day 15, mean CRP, HAQ-DI and DAS28-4(ESR) significantly increased from BL for interrupted vs continuous tx. After tofacitinib reinitiation for 28 days (Day 43), changes in CRP, HAQ-DI and DAS28-4(ESR) were similar between grps and approached BL levels. Adverse events (AEs) were experienced by 35.4% and 49.5% of pts receiving interrupted and continuous tx, respectively. The most frequent treatment-emergent AEs were bronchitis and upper respiratory tract infection (each AE: 6 pts) and vaccination-related immunisation reaction, myalgia and rash (each AE: 5 pts). Serious AEs occurred in 3 pts (3%) in each grp. In total, 1 pt (1%), in the interrupted tx grp, discontinued due to a study-drug related AE; no pts discontinued due to disease flare.
Conclusions Efficacy of tofacitinib 10 mg BID can be reestablished following loss of efficacy during temporary (2 weeks) tx discontinuation in pts with RA. Pts receiving continuous tx maintained efficacy throughout the study. Further investigations are required.
Winthrop KL et al. Ann Rheum Dis 2016; 75: 687–695.
Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Haines of CMC and was funded by Pfizer Inc.
Disclosure of Interest J. Kaine Speakers bureau: Bristol-Myers Squibb, Pfizer Inc, J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc