POS0658 GEOGRAPHIC VARIATION OF EFFICACY IN THE FILGOTINIB RHEUMATOID ARTHRITIS PROGRAM
Authors: M. H. Buch, T. Matsubara, B. Combe, A. Pechonkina, Y. Tan, Z. Yin, J. Hong, R. Besuyen, A. Gomez-Centeno
Journal: Annals of the Rheumatic Diseases (2021)

Background: The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) across the FIL clinical program. 1–3 Objectives: To assess FIL efficacy across geographic regions. Methods: Pooled data from patients (pts) meeting 2010 ACR/EULAR RA criteria randomised to once-daily FIL 200 mg (FIL200), FIL100 mg (FIL100), or placebo (PBO) with background conventional synthetic disease-modifying antirheumatic drugs in DARWIN 1 (P2; up to week [W]12) and FINCH 1–2 (P3; up to W24) studies were evaluated. Data were analysed by region: North America, South and Central America, Western Europe, Eastern Europe, Asia, South East (SE) Asia, and Other. W12 American College of Rheumatology 20% improvement (ACR20) and W24 Disease Activity Score in 28 joints (C-reactive protein) (DAS28[CRP]) &lt;2.6 and ≤3.2 response rates were analysed by a logistic regression model. Change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at W12 was analysed by a mixed-effects model for repeated measures. Analyses were exploratory and not adjusted for multiplicity. Results: Despite high PBO response rates in Eastern Europe and South and Central America, greater proportions of pts receiving FIL200 or FIL100 vs PBO achieved ACR20 at W12 ( P &lt;0.05) in all regions, except Other (with lowest sample size, n = 69), where both FIL doses were numerically greater than PBO (Table 1). At W12, least-squares mean CFB in HAQ-DI improved for pts receiving FIL200 or FIL100. vs PBO ( P &lt;0.05) in all regions, except SE Asia, where improvement was numeric (Table 1). Table 1. Proportion of pts achieving ACR20 and LSM change from baseline HAQ-DI at week 1 ACR20 HAQ-DI FIL200 FIL100 FIL200 FIL100 FIL200 FIL100 North America 64.8 * 58.3 * 33.8 −0.63 * −0.58 * −0.34 n = 455 (56.7, 72.9) (50.3, 66.4) (26.0, 41.6) (−0.70, −0.56) (−0.65, −0.51) (−0.41, −0.27) South and Central America 77.2 77.3 57.4 −0.77 * −0.67 * −0.43 n = 283 (68.1, 86.3) † (65.8, 86.2) † (46.9, 68.0) (−0.85, −0.68) (−0.75, −0.59) (−0.52, −0.35) Western Europe 69.4 * 68.3 * 24.4 −0.69 * −0.61 * −0.28 n = 135 (55.5, 83.3) (52.8, 83.8) (10.8. 38.1) (−0.80, −0.58) (−0.73, −0.49) (−0.40, −0.17) Eastern Europe 77.1 * 69.1 * 54.6 −0.62 * −0.51 * −0.34 n = 822 (71.9, 82.3) (63.5, 74.7) (48.5, 60.7) (−0.68, −0.56) (−0.57, −0.45) (−0.40, −0.28) Asia 81.0 * 60.0 † 37.7 −0.83 * −0.61 † −0.42 n = 236 (71.7, 90.3) (48.6, 71.4) (26.2, 49.1) (−0.92, −0.73) (−0.70, −0.52) (−0.52, −0.33) South East Asia 70.2 † 71.1 † 39.5 −0.61 −0.57 −0.45 n = 135 (56.1, 84.4) (56.8, 85.5) (23.8, 55.3) (−0.73, −0.49) (−0.69, −0.45) (−0.58, −0.33) Other 60.0 52.4 39.1 −0.56 ‡ −0.60 ‡ −0.33 n = 69 (38.8, 81.2) (28.6, 76.1) (17.0, 61.2) (−0.72, −41) (−0.76, −0.43) (−0.49, −0.17) Overall 73.4 * 66.4 * 45.3 −0.71 * −0.61 * −0.40 N = 2135 (70.1, 76.8) (62.9, 70.0) (41.5, 49.0) (−0.76, −0.66) (−0.66, −0.56) (−0.45, −0.35) Includes only patients initially randomised to the treatment groups in each study for the comparison of interest. ACR20 presented as percentage (95% CI); 95% CI was based on normal approximation method with a continuity correction; P values calculated from the logistic regression.HAQ-DI presented as LSM (95% CI); LSM, 95% CI, and P value calculated from a mixed-effects model for repeated measures.*P &lt;0.001, †P &lt;0.01, ‡P &lt;0.05; not adjusted for multiplicity. ACR20, American College of Rheumatology 20% improvement; CI, confidence interval; FIL, filgotinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least square mean; PBO, placebo. At W24, DAS28(CRP) &lt;2.6 and ≤3.2 response rates were higher for both doses of FIL vs PBO ( P &lt;0.05) in all regions, with the exception of Other, where PBO was higher than FIL100 for DAS28(CRP) &lt;2.6 (Figure 1). Conclusion: In exploratory analyses, ACR20, DAS28(CRP) &lt;2.6 and ≤3.2 response rates and HAQ-DI scores varied between regions; however, no stable trend was shown in any particular region. Small pt numbers in some subgroups may confound statistical analysis. References: [1]Genovese et al. JAMA . 2019;322:315–25. [2]Westhovens et al. Ann Rheum Dis . 2021; online first. [3]Combe et al. Ann Rheum Dis . 2021; online first. Disclosure of Interests: Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB., Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB., Tsukasa Matsubara Speakers bureau: Pfizer Japan, Nichi-Iko, Astellas, Meiji Seika, Bristol-Myers Squibb, AbbVie GK, Janssen, Chugai, Eisai, AYUMI, Bernard Combe Speakers bureau: BMS; Eli Lilly &amp; Co.; Gilead Sciences, Inc.; MSD; Pfizer; Roche-Chugai; and UCB, Consultant of: AbbVie; Eli Lilly &amp; Co.; Gilead Sciences, Inc.; Janssen; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Jaehyung Hong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, Antonio Gomez-Centeno Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly &amp; Co., Gebro, Janssen, Menarini, Merck Sharp &amp; Dohme, Pfizer, Roche, Rubio, Sanofi, and UCB, Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly &amp; Co., Gebro, Gilead Sciences, Inc., Hospira, Merck Sharp &amp; Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi, Grant/research support from: Boehringer Ingelheim, Celltrion, Eli Lilly &amp; Co., Galapagos NV, Gilead Sciences, Inc., Novartis, Pfizer, Roche, Sanofi, UCB, YL Biologics