The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of Phase 3 studies

Abstract

Background: The effects of filgotinib on patient-reported outcomes (PROs) from 3 trials in patients with active rheumatoid arthritis were investigated.

Methods: Methotrexate (MTX)-naïve patients received filgotinib 200 or 100 mg plus MTX (FIL200+MTX, FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX monotherapy through 52 weeks (NCT02886728). Patients with inadequate response (IR) to MTX (MTX-IR) received FIL200+MTX, FIL100+MTX, adalimumab 40 mg +MTX (ADA+MTX), or placebo (PBO)+MTX (rerandomized to FIL200+MTX or FIL100+MTX at week 24) through 52 weeks (NCT02889796). Patients with IR to biologic disease-modifying antirheumatic drugs (bDMARD-IR) received FIL200 or FIL100 or PBO with background stable conventional synthetic (cs) DMARDs for up to 24 weeks (NCT02873936). PROs included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical/mental component summary (PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and Patient Global Assessment of Disease Activity (PtGA). Data are reported as least-squares mean changes from baseline with standard error to the timepoint representing each study's primary endpoint. All statistical comparisons are of filgotinib groups vs their respective control groups.

Results: At week 24, among MTX-naïve patients, change from baseline (standard deviation) in HAQ-DI was - 1.00 (0.03; P < 0.001) with FIL200+MTX, - 0.94 (0.04; P < 0.01) with FIL100+MTX, and - 0.91 (0.04; P < 0.05) with FIL200 alone compared with - 0.81 (0.03) with MTX alone. At week 12, among MTX-IR patients, change from baseline in HAQ-DI was - 0.69 (0.04; P < 0.001 vs PBO+MTX, P < 0.05 vs ADA) with FIL200+MTX, - 0.57 (0.04; P < 0.001 vs placebo) with FIL100+MTX, and - 0.60 (0.04) with ADA vs - 0.40 (0.04) with PBO+MTX. At week 12, among bDMARD-IR patients, change from baseline in HAQ-DI was - 0.50 (0.06; P < 0.001) with FIL200+csDMARD and - 0.46 (0.05; P < 0.001) with FIL100+csDMARD vs - 0.19 (0.06) with placebo+csDMARD. Changes in SF-36 PCS and MCS, FACIT-Fatigue, WPAI, and PtGA tended to favor filgotinib over PBO, MTX, and ADA. Greater proportions of patients experienced clinically meaningful differences with either dosage of FIL in combination with csDMARDs (including MTX) and with FIL200 monotherapy vs comparators.

Conclusions: Filgotinib provided improvements in PROs across patient populations. These findings suggest filgotinib can be an effective treatment option for patients with insufficient response to MTX or bDMARDs and patients who are MTX-naïve.

Trial registration: ClinicalTrials.gov , FINCH 1, NCT02889796 , first posted September 7, 2016; FINCH 2, NCT02873936 , first posted August 22, 2016, retrospectively registered; FINCH 3, NCT02886728 , first posted September 1, 2016, retrospectively registered.

Keywords: FACIT-Fatigue; Filgotinib; HAQ-DI; Patient-reported outcomes; SF-36; WPAI.

Conflict of interest statement

COB reports grant/research support from BMS; is a consultant for AbbVie; BMS; Eli Lilly & Co.; Gilead Sciences, Inc.; Janssen; Pfizer; Regeneron; and Sanofi. DW has financial ties with Eli Lilly & Co.; Gilead Sciences, Inc.; Pfizer; and Roche. PN reports financial relationships with AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly & Co., Gilead, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi. SJL, LY, and HH are employees and shareholders of Gilead Sciences, Inc. JMK is an employee of Galapagos NV. BC receives grant/research support from Novartis, Pfizer, and Roche-Chugai; is a consultant for AbbVie; Celltrion; Eli Lilly & Co.; Galapagos; Gilead Sciences, Inc.; Janssen; Roche-Chugai; and is on the speakers bureau for BMS; Eli Lilly & Co.; Gilead Sciences, Inc.; MSD; Pfizer; Roche-Chugai.

© 2021. The Author(s).

Figures

Fig. 1

Proportion of patients achieving MCID for HAQ-DI in A MTX-naïve patients, B MTX-IR patients, and C and bDMARD-IR patients; proportion of patients who achieved HAQ-DI score of ≤ 0.5 by visit D MTX-naïve, E MTX-IR, and F bDMARD-IR. Comparison with PBO or MTX: ***P < 0.001, **P < 0.01, *P < 0.05. Comparison with ADA: †P < 0.05. All P values are exploratory (not adjusted for multiplicity) and were from logistic regression with treatment groups and stratification factors in the model. A nonresponder imputation was used for patients with missing data. MCID was defined as a ≥ 0.22-point reduction from baseline. In the MTX-IR trial, patients on PBO were rerandomized to FIL 200 or 100 mg at week 24. The study in bDMARD-IR patients ended at week 24. ADA, adalimumab; bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; DMARD, disease-modifying antirheumatic drug; FIL, filgotinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least-squares; MCID, minimal clinically important difference; MTX, methotrexate; PBO, placebo

Fig. 2

Proportion of patients achieving MCID for SF-36 PCS in A MTX-naïve patients, B MTX-IR patients, and C bDMARD-IR patients; proportion of patients achieving MCID for SF-36 MCS in D MTX-naïve, E MTX-IR, and F bDMARD-IR. Comparison with PBO or MTX: ***P < 0.001, **P < 0.01, *P < 0.05. All P values are exploratory (not adjusted for multiplicity) and were from logistic regression with treatment groups and stratification factors in the model. A nonresponder imputation was used for patients with missing data. MCID was defined as a ≥ 2.5-point increase from baseline. In the MTX-IR trial, patients on PBO were rerandomized to FIL 200 or 100 mg at week 24. The study in bDMARD-IR patients ended at week 24. ADA, adalimumab; bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; DMARD, disease-modifying antirheumatic drug; FIL, filgotinib; MCID, minimal clinically important difference; MCS, mental component score; MTX, methotrexate; PBO, placebo; PCS, physical component score; SF-36, Medical Outcomes Study 36-Item Short Form

Fig. 3

LS mean change from baseline in SF-36 individual domains by visit in A MTX-naïve patients, filgotinib dosing regimens compared with MTX: B MTX-IR patients, and filgotinib dosing regimens compared with placebo and adalimumab C bDMARD-IR patients, filgotinib dosing regimens compared with placebo. Concentric octagons represent the LS mean change from baseline in the SF-36 domain score. Comparison with placebo or MTX: ***P < 0.001, **P < 0.01, *P < 0.05. Comparison with ADA: †††P < 0.001, ††P < 0.01. All P values are exploratory (not adjusted for multiplicity) and were from the MMRM including treatment, visit (as categorical), treatment by visit, stratification factors, baseline value as fixed effects, and patients being the random effect. In the MTX-IR study, patients receiving PBO were rerandomized to FIL 200 or 100 mg at week 24. The bDMARD-IR study ended at week 24. ADA, adalimumab; BP, bodily pain; bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; DMARD, disease-modifying antirheumatic drug; FIL, filgotinib; GH, general health; LS, least-squares; MH, mental health; MMRM, mixed-effects model for repeated measures; MTX, methotrexate; PBO, placebo; PF, physical functioning; R-E, role-emotional; R-P, role-physical; SF, social functioning; SF-36, Medical Outcomes Study 36-Item Short Form; V, vitality

Fig. 4

Proportion of patients achieving MCID for FACIT-Fatigue in A MTX-naïve patients, B MTX-IR patients, and C bDMARD-IR patients. Comparison with placebo or methotrexate: ***P < 0.001, **P < 0.01, *P < 0.05. Comparison with adalimumab: †P < 0.05. All P values are exploratory (not adjusted for multiplicity) and were from logistic regression with treatment groups and stratification factors in the model. A nonresponder imputation was used for patients with missing data. MCID was defined as a ≥ 4-point increase from baseline. In the MTX-IR study, patients on PBO were rerandomized to FIL 200 or 100 mg at week 24. The bDMARD-IR study ended at week 24. ADA, adalimumab; bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; DMARD, disease-modifying antirheumatic drug; FACIT, Functional Assessment of Chronic Illness Therapy; FIL, filgotinib; MCID, minimal clinically important difference; MTX, methotrexate; PBO, placebo