POS0658 GEOGRAPHIC VARIATION OF EFFICACY IN THE FILGOTINIB RHEUMATOID ARTHRITIS PROGRAM

Abstract

Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) across the FIL clinical program.1–3Objectives: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]) <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 <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 <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 1ACR20HAQ-DIFIL200FIL100FIL200FIL100FIL200FIL100North America64.8*58.3*33.8−0.63*−0.58*−0.34n = 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 America77.277.357.4−0.77*−0.67*−0.43n = 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 Europe69.4*68.3*24.4−0.69*−0.61*−0.28n = 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 Europe77.1*69.1*54.6−0.62*−0.51*−0.34n = 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)Asia81.0*60.0†37.7−0.83*−0.61†−0.42n = 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 Asia70.2†71.1†39.5−0.61−0.57−0.45n = 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)Other60.052.439.1−0.56‡−0.60‡−0.33n = 69(38.8, 81.2)(28.6, 76.1)(17.0, 61.2)(−0.72, −41)(−0.76, −0.43)(−0.49, −0.17)Overall73.4*66.4*45.3−0.71*−0.61*−0.40N = 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 <0.001, †P <0.01, ‡P <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) <2.6 and ≤3.2 response rates were higher for both doses of FIL vs PBO (P <0.05) in all regions, with the exception of Other, where PBO was higher than FIL100 for DAS28(CRP) <2.6 (Figure 1).Conclusion:In exploratory analyses, ACR20, DAS28(CRP) <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.