Dataset Information

Efficacy of Filgotinib in Patients with Ulcerative Colitis by Line of Therapy in the Phase 2b/3 SELECTION Trial.

ABSTRACT:

Background and aims

The efficacy of new therapies for ulcerative colitis [UC] is usually influenced by previous biologic use. These post hoc analyses of SELECTION, a placebo-controlled phase 2b/3 trial in patients with moderately to severely active UC, evaluated the efficacy of filgotinib, an oral Janus 1 kinase preferential inhibitor, with respect to prior biologic failure.

Methods

The effect of filgotinib 200 mg (FIL200) relative to placebo was compared in biologic-naïve and biologic-failed patient groups, and in further subgroups by number of failed biologics [1 or >1], biologic mechanism of action [MoA] classes [1 or 2] and tumour necrosis factor [TNF] antagonists [1 or >1]. Odds ratios [ORs] for clinical remission at week 10 [induction] and hazard ratios [HRs] for protocol-specific disease worsening [PSDW] from week 11 to week 58 [maintenance] were calculated.

Results

At week 10, FIL200-treated patients were more likely to achieve clinical remission than placebo-treated patients in the biologic-naïve (OR [95% confidence interval, CI]: 1.98 [1.14-3.44]) and biologic-failed (3.91 [1.33-11.48]) groups. During maintenance, FIL200-treated patients had a reduced risk of PSDW in the biologic-naïve (HR [95% CI]: 0.22 [0.11-0.44]) and biologic-failed (0.22 [0.12-0.40]) groups, and in all biologic-failed subgroups (except >1 TNF antagonist failure). The data suggest that the likelihood of PSDW at week 58 increased with increasing numbers of failed biologics.

Conclusions

FIL200 induced and maintained benefits relative to placebo regardless of previous biologic use; however, the estimated therapeutic benefit was greatest in biologic-naïve patients and patients previously treated with one biologic or biologic MoA class. [ClinicalTrials.gov: NCT02914522].

SUBMITTER: Dotan I

PROVIDER: S-EPMC10441561 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Efficacy of Filgotinib in Patients with Ulcerative Colitis by Line of Therapy in the Phase 2b/3 SELECTION Trial.

Dotan Iris I Feagan Brian G BG Taliadouros Virginia V Oortwijn Alessandra A Rudolph Christine C de Haas Angela A Santermans Eva E Hsieh Jeremy J Peyrin-Biroulet Laurent L Hibi Toshifumi T

Journal of Crohn's & colitis 20230801 8

<h4>Background and aims</h4>The efficacy of new therapies for ulcerative colitis [UC] is usually influenced by previous biologic use. These post hoc analyses of SELECTION, a placebo-controlled phase 2b/3 trial in patients with moderately to severely active UC, evaluated the efficacy of filgotinib, an oral Janus 1 kinase preferential inhibitor, with respect to prior biologic failure.<h4>Methods</h4>The effect of filgotinib 200 mg (FIL200) relative to placebo was compared in biologic-naïve and bio ...[more]

PMID: 36928705

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Project description:Background and aimsCorticosteroid-free remission is an important treatment goal for patients with ulcerative colitis [UC]. The corticosteroid-sparing effects of filgotinib, an oral, Janus kinase 1 preferential inhibitor, were assessed in SELECTION, a placebo-controlled, phase 2b/3 trial in moderately to severely active UC.MethodsThese post hoc analyses assessed 1-, 3-, 6-, and 8-month rates of corticosteroid-free clinical remission at Week 58 and change in median daily prednisone-equivalent dose over time. A matching-adjusted indirect comparison [MAIC] of maintenance studies assessed corticosteroid-free remission with filgotinib 200 mg, intravenous vedolizumab, subcutaneous vedolizumab, and oral tofacitinib.ResultsThe Maintenance Study full analysis set included 199 patients receiving filgotinib 200 mg and 98 receiving placebo. Among patients receiving corticosteroids at Maintenance Study baseline, at Week 58, 30.4%, 29.3%, 27.2%, and 21.7% receiving filgotinib had been in corticosteroid-free remission for ≥1, ≥3, ≥6, or ≥8 months, respectively, versus 6.4% receiving placebo across thresholds [p <0.05]. Median daily prednisone-equivalent dose decreased from 17.5 mg/day to 10.0 mg/day with filgotinib treatment during the Maintenance Study. Based upon the MAIC, filgotinib was associated with greater likelihood of corticosteroid-free clinical remission versus intravenous vedolizumab (odds ratio [OR], 15.2; 95% confidence interval [CI], 1.6-139.9; p <0.05]) and similar odds to subcutaneous vedolizumab [OR, 3.8; CI, 0.2-63.8; p = 0.36] in biologic-naïve patients, and similar odds to tofacitinib overall [OR, 2.0; 0.4-9.1; p = 0.39].ConclusionsFilgotinib 200 mg demonstrated corticosteroid-sparing effects and maintained corticosteroid-free clinical remission in patients with UC. MAIC results should be interpreted cautiously given the large CIs and differences in study design and patient populations. [ClinicalTrials.gov: NCT02914522].

Project description:BackgroundFilgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long-term treatment response trajectories may improve UC management.ObjectiveWe aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time.MethodsIn these post hoc analyses of SELECTION, group-based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom-based patient trajectories using data from patients who responded to filgotinib 200 or 100 mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient-level multi-component endpoint of comprehensive disease control (CDC) was assessed in each group.ResultsGBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1 year), were receiving filgotinib 200 mg and were biologic-naive versus the relapsing trajectory groups (4%-9% vs. 4%-5%; 43%-65% vs. 36%-46%; 54%-70% vs. 35%-58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%-32% vs. 0%-7%).ConclusionsBeneficial long-term response trajectories and achievement of CDC with filgotinib were associated with being biologic-naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC.ClinicaltrialsGov identifierNCT02914522.

Dataset Information

Efficacy of Filgotinib in Patients with Ulcerative Colitis by Line of Therapy in the Phase 2b/3 SELECTION Trial.

Background and aims

Methods

Results

Conclusions

Publications

Efficacy of Filgotinib in Patients with Ulcerative Colitis by Line of Therapy in the Phase 2b/3 SELECTION Trial.

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