Prevention of Radiographic Progression in Higher-Risk Patients with Rheumatoid Arthritis Using Filgotinib in Phase III Studies: Narrative Review of Post Hoc Analyses

Abstract

Filgotinib is an oral preferential Janus kinase 1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH 1) and vs MTX in MTX-naïve patients with RA (FINCH 3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from post hoc analyses of phase 3 trials of filgotinib that examined subgroups with 4 PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4 PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200 mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4 PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.

Keywords: Adalimumab; Filgotinib; Methotrexate; Poor prognostic factors; Rheumatoid arthritis.

Fig. 1

Radiographic progression (FINCH 1, MTX-IR patients) through a week 24, and b week 52 [11, 21]. ADA adalimumab, FIL filgotinib, FIL100 FIL 100 mg, FIL200 FIL 200 mg, IR inadequate response, JSN joint space narrowing, LS least squares, mTSS modified total Sharp score, MTX methotrexate, PBO placebo, PPF poor prognostic factor. Data from Combe et al. [11], Springer Nature, and Combe et al. [21], Springer Nature

Fig. 2

Findings from FINCH 3 (MTX-naïve patients); a change from baseline in mTSS and components in overall population at week 24, b change from baseline in mTSS and components in overall population at week 52, c mTSS change in patients with 4 PPFs vs overall population at week 24, and d mTSS change in patients with 4 PPFs and overall population at week 52 [12, 22]. a, b ***Nominal p < 0.001; **nominal p < 0.01; *nominal p < 0.05; for supportive analysis without adjustment for multiplicity. Error bars represent 95% CI. For mTSS, week 24 includes only data from campaign A and week 52 includes data from campaign A and B. Week 52 n values are not provided for mTSS change from baseline, as the analysis included both campaign A (through week 24) and campaign B (through week 52 including re-reading of baseline and week 24). c, d *Nominal p < 0.05; **nominal p < 0.01; ***nominal p < 0.001. CI confidence interval, ES erosion score, FIL filgotinib, FIL100 FIL 100 mg, FIL200 FIL 200 mg, JSN joint space narrowing, LSM least squares mean, mono monotherapy, mTSS modified total Sharp score, MTX methotrexate, PPF poor prognostic factor. Reproduced from Westhovens et al. [12] with permission from BMJ Publishing Group Ltd. (link to license), and Aletaha et al. [22] with permission from BMJ Publishing Group Ltd (link to license)

Fig. 3

Change from baseline in mTSS at week 24 and 52 in a MTX-IR and b MTX-naïve patients [23]. All p values are nominal vs PBO or ADA at week 24 and vs ADA at week 52 in FINCH 1 and vs MTX mono in FINCH 3. ADA at week 24 is out of scope for statistical calculation. ADA adalimumab, e-NRRP estimated nonrapid radiographic progression, e-RRP estimated rapid radiographic progression, FIL filgotinib, FIL100 FIL 100 mg, FIL200 FIL 200 mg, IR inadequate response, mono monotherapy, mTSS modified total Sharp score, MTX methotrexate, PBO placebo, W week. Reproduced from Tanaka et al. [23], Springer Nature (link to license)

Fig. 4

Proportions of MTX-IR patients (FINCH 1) with 4 PPFs and with < 4 PPFs with no radiographic progression (change from baseline mTSS ≤ 0.5) at week 24 [21]. All treatment groups also received MTX. ADA adalimumab, FIL filgotinib, FIL100 FIL 100 mg, FIL200 FIL 200 mg, IR inadequate response, mTSS modified total Sharp score, MTX methotrexate, PBO placebo, PPF poor prognostic factor. Adapted from Combe et al. [21], Springer Nature (link to license)