Geographic Analysis of the Safety and Efficacy of Filgotinib in Rheumatoid Arthritis

Abstract

Introduction: Global clinical trials in rheumatoid arthritis (RA) often do not recruit enough patients from diverse racial and ethnic backgrounds to identify any potential differences in treatment outcome across such groups. To overcome this limitation, using data from five previous clinical trials and two ongoing trial extensions, this study aimed to assess the efficacy and safety of filgotinib in patients with RA across geographic regions.

Methods: This was a post hoc, exploratory analysis of data from male and female patients with RA meeting the 2010 RA criteria as defined by the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology. Data were analyzed from phase 2 (DARWIN 1-2) and phase 3 (FINCH 1-3) clinical trials, as well as two long-term extension studies (DARWIN 3, FINCH 4), of filgotinib. Efficacy endpoints included ACR 20%/50%/70% improvement (ACR20/50/70) responses, disease activity score in 28 joints using C-reactive protein [DAS28(CRP)], Clinical Disease Activity Index scores, Boolean remission, and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety data were presented as exposure-adjusted incidence rates per 100 patient-years of exposure of treatment-emergent adverse events.

Results: Compared with placebo, at week 12 a greater proportion of patients receiving filgotinib 200 mg (FIL200) or 100 mg (FIL100) achieved ACR20 (p < 0.01), with similar outcomes in most regions. Overall, the reduction in HAQ-DI with FIL200 or FIL100 was greater than with placebo (p < 0.05) at week 12. Compared with placebo, at week 24 the proportions of patients achieving DAS28(CRP) ≤ 3.2 were greater for both doses of FIL, as seen in most regions (p < 0.01). Safety outcomes did not indicate regional or ethnic differences in the safety profile of filgotinib.

Conclusion: Filgotinib efficacy and safety in patients with RA were generally consistent across geographic regions.

Gov trial registration numbers: NCT02889796; NCT02873936; NCT02886728; NCT03025308; NCT01888874; NCT01894516; NCT02065700.

Keywords: Adverse effects; Disease-modifying antirheumatic drug; Filgotinib; Outcomes; Rheumatoid arthritis.

© 2022. The Author(s).

Figures

Fig. 1

Pooled efficacy data for a ACR20, b HAQ-DI, c DAS28(CRP) ≤ 3.2, and d DAS28(CRP) < 2.6. Other = South Africa, New Zealand, Australia, and Israel. For ACR20 and DAS28(CRP), 95% CIs and P values were calculated from the logistic regression with treatment groups, stratification factors, subgroup, study, and treatment by subgroup included in the model. For HAQ-DI, the MMRM included treatment, visit (as categorical variable), subgroup, treatment by visit, treatment by subgroup, baseline value, stratification factors, and study as fixed effects, and patients as the random effect. LS mean, 95% CI, and P value were obtained from the MMRM. The common stratification factor is prior exposure to bDMARDs for the analysis through week 12 and includes prior exposure to bDMARDs and presence of anti-cyclic citrullinated peptide or rheumatoid factor for the analysis through week 24. ACR20 American College of Rheumatology 20% improvement, bDMARD biologic disease-modifying antirheumatic drug, CI confidence interval, DAS28(CRP) disease activity score in 28 joints using C-reactive protein, FIL100/200 filgotinib 100 mg/200 mg, HAQ-DI Health Assessment Questionnaire–Disability Index, LS least squares, MMRM mixed effects model for repeated measures, OR odds ratio

Fig. 2

EAIR of a serious infections, b herpes zosterb, c malignancy other than NMSC (long-term, as-treated), d major adverse cardiovascular events, and e venous thromboembolism. Other = South Africa, New Zealand, Australia, and Israel. aThe Poisson model was not adjusted by study, except when any study had zero events within the treatment. bData reported in Winthrop et al. 2022 [19]. CI confidence interval, EAIR exposure-adjusted incidence rate, FIL100/200 filgotinib 100 mg/200 mg, NMSC nonmelanoma skin cancer, PYE patient-years of exposure