Background Tofacitinib is an oral JAK inhibitor for the treatment (tx) of rheumatoid arthritis (RA). Studies have shown diminishing response to tx in RA patients (pts) when cycling through TNF inhibitors. Prior analyses assessed tofacitinib in csDMARD-inadequate response (IR) pts vs overall bDMARD-IR pts.
Objectives To compare tofacitinib safety and efficacy in RA pts who have previously failed tx (lack of efficacy and/or safety reasons) with csDMARDs, with pts who failed tx with either 1 or ≥2 prior bDMARDs.
Methods Data from pts who received ≥1 dose of tofacitinib in 19 RA studies up to 96 months (2 Phase [P] 1; 9 P2; 6 P3; 2 LTE studies [1 LTE ongoing; data as of March 2015]) were used in this analysis. Data were pooled across all 19 studies for safety assessments in the All RA population: csDMARD-IR, n=4377; bDMARD-IR, n=838 (1 bDMARD-IR, n=533; ≥2 bDMARD-IR n=305). Safety was also assessed up to 24 months in pts randomised to tofacitinib 5 or 10 mg BID or placebo (PBO) in a pooled P2/P3 randomised controlled trial (RCT) population (8 P2, 6 P3 studies; csDMARD-IR, n=3328; bDMARD-IR, n=782). Incidence rates (pts with events/100 pt-years) were calculated for serious AEs (SAEs), serious infections (SIs) and herpes zoster (HZ). Efficacy was assessed by pts achieving ACR20 response and DAS28-4(ESR) ≤3.2 at Month 3 in a pooled P3 RCT population (csDMARD-IR, n=2375; bDMARD-IR, n=664).
Results Prior to tofacitinib tx, bDMARD-IR pts had longer RA duration, greater disease burden and more corticosteroid use vs csDMARD-IR pts. SAEs were more common among bDMARD-IR vs csDMARD-IR pts in both the P2/P3 RCT and the All RA populations; SAE rates were not higher in pts failing ≥2 bDMARDs vs 1 bDMARD (Table). Incidence rates for SIs were generally greater in pts with IR to bDMARDs vs csDMARDs in the All RA population, but generally lower in pts with IR to 1 or ≥2 bDMARDs vs csDMARDs in the P2/P3 RCT population; incidence with 5 mg BID was lower for 1 vs ≥2 bDMARDs in the P2/P3 RCT population. Incidence rates for HZ were similar between pts with IR to csDMARDs or 1 bDMARD, but appeared numerically greater in pts with IR to ≥2 bDMARDs in both the P2/P3 RCT and the All RA populations. A similar pattern was observed across tofacitinib and PBO groups. Efficacy at Month 3 in the P3 RCT population was greater with both tofacitinib doses vs PBO. Although absolute response was smaller in pts with IR to bDMARDs vs csDMARDs, generally similar efficacy was observed in pts with IR to 1 or ≥2 bDMARDs (Table).
Conclusions SAEs and SIEs were more common in tofacitinib- and PBO-treated pts with IR to bDMARDs vs csDMARDs; increased risk was generally not observed with increasing number of prior bDMARDs. HZ risk appeared greater with ≥2 bDMARDs vs 1 bDMARD. Efficacy was greater with tofacitinib vs PBO for csDMARD-IR and bDMARD-IR pts, with similar response observed in pts with IR to ≥2 or 1 bDMARD. These data support the use of tofacitinib in different lines of therapy, although the analysis is limited by smaller sample size in some groups.
Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by N Jones of CMC and was funded by Pfizer Inc.
Disclosure of Interest C. Charles-Schoeman Grant/research support from: AbbVie, Bristol-Myers Squibb, Pfizer Inc, Consultant for: Amgen, Pfizer Inc, Regeneron-Sanofi, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Pfizer Inc, Employee of: Corrona, LLC, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Strengholt Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, Medimmune, MSD, Novartis, Pfizer Inc, Roche, Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche