ANALYSIS OF THE IMPACT OF TOFACITINIB TREATMENT ON WEIGHT IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: A prior post hoc analysis of tofacitinib clinical trial data reported improvements in rheumatoid arthritis (RA) outcomes with tofacitinib vs placebo (PBO) through Month (M)6, regardless of baseline (BL) body mass index (BMI). Objectives: To assess change from BL (Δ) in BMI, and disease activity by BL BMI status, in patients (pts) with moderate/severe RA receiving tofacitinib through M12. Methods: This post hoc analysis included data pooled from Phase 3 and 3b/4 studies of pts who were methotrexate-naïve (NCT01039688) or inadequate responders to conventional synthetic (cs) or biologic DMARDs (NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT02187055; NCT02831855). Pts received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or 11 mg once daily (QD), ± csDMARDs, or PBO. Least squares (LS) mean ΔBMI (linear mixed model repeated measures; observed cases) was summarised for all treatment groups at M3/6/12 (M3/6 only for tofacitinib 11 mg QD and PBO). Other assessments at M3/6/12 included ΔBMI ± BL concomitant glucocorticoids (GCs) or antidepressants (descriptive statistics), LS mean ΔDAS28-4(ESR) stratified by BL BMI status (<25, ≥25–<30, ≥30), and correlations between LS mean ΔBMI and ΔDAS28-4(ESR). Results: In total, 2349, 1611, 694 and 681 pts received tofacitinib 5 mg BID, 10 mg BID, 11 mg QD or PBO, respectively. Demographics/baseline characteristics were generally similar across treatments, except for some numerical differences in the tofacitinib 11 mg QD group, eg fewer female pts, more White pts and fewer pts receiving concomitant GCs, compared with other treatment groups. At M3/6, LS mean BMI significantly increased from BL with all tofacitinib doses vs PBO (all p<0.05); LS mean ΔBMI was greatest with 10 mg BID and lowest with 11 mg QD ( Figure 1a ). LS mean ΔBMI was greater in pts receiving tofacitinib as monotherapy vs combination therapy at M3/6/12 ( Figure 1b ). ΔBMI was generally similar in pts receiving treatment ± concomitant GCs or antidepressants (data not shown). Improvements in DAS28-4(ESR) were observed in each BL BMI status group at M3/6/12 and were greatest with all tofacitinib doses vs PBO. LS mean ΔDAS28-4(ESR) was generally numerically highest for pts with BMI <25 and numerically lowest for pts with BMI >30, for all tofacitinib doses. LS mean ΔDAS28-4(ESR) was generally greatest with tofacitinib 10 mg BID and 11 mg QD vs 5 mg BID across BL BMI status groups ( Figure 1c ). Across treatments, model-adjusted associations between LS mean ΔDAS28-4(ESR) and ΔBMI were weak (correlation coefficients all <0.3; Table 1 ). Table 1. Correlations between LS mean ΔDAS28-4(ESR) and ΔBMI through M12 Tofacitinib 5 mg BID Tofacitinib 10 mg BID Tofacitinib 11 mg QD PBO N Correlation coefficient N Correlation coefficient N Correlation coefficient N Correlation coefficient M3 2021 0.1169 1348 0.1240 641 0.0907 554 0.0783 M6 1918 0.1305 1270 0.1397 611 0.0438 150 0.1556 M12 1455 0.1213 874 0.1826 - - - - Slopes for associations between LS mean ΔBMI and ΔDAS28-4(ESR) were significantly different from 0 at M3/6/12 with tofacitinib 5 and 10 mg BID (all p<0.05). Correlations were analysed by a general linear model method, which included BL age, gender, race and RA duration. For pts receiving tofacitinib 11 mg QD in ORAL Shift (NCT02831855), only data to M6 were included. Pts who advanced from PBO to tofacitinib were not analysed post-advancement DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; N, number of pts analysed Conclusion: LS mean ΔBMI was greater with tofacitinib (all doses) vs PBO at M3/6, and with tofacitinib monotherapy vs combination therapy at M3/6/12. Improvements in DAS28-4(ESR) were seen across all BL BMI status groups. BMI increases with tofacitinib were only weakly associated with DAS28-4(ESR) improvements. The relationship between disease activity and ΔBMI requires further investigation. REFERENCES: [1]Dikranian et al. Arthritis Rheumatol 2018; 69 (S10): Abs 2371. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Jürgen Wollenhaupt Speakers bureau: Pfizer Inc, Consultant of: Pfizer Inc, Jacques Morel Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Claire Daien Consultant of: Abivax, Grant/research support from: AbbVie, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Novartis, Pfizer Inc, Sandoz, Adeline Ruyssen-Witrand Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Mylan, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Mylan, Pfizer Inc, Cédric Lukas Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc, Sanofi Genzyme, UCB, Grant/research support from: Novartis, Pfizer Inc, Christophe Richez Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Mylan, Pfizer Inc, Grant/research support from: Biogen, Eli Lilly, Glenmark, Nordic Pharma, Roche, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Magali CROS Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 1148Session: Rheumatoid arthritis - non biologic treatment and small molecules (Publication Only)