Efficacy and Safety of Filgotinib as Induction Therapy for Patients with Moderately to Severely Active Ulcerative Colitis: Results from the Phase 2b/3 SELECTION Study

Introduction Filgotinib (FIL) is a Janus kinase 1 inhibitor being investigated for ulcerative colitis (UC).

Aims and Methods The SELECTION (NCT02914522) Induction Studies evaluated efficacy and safety of FIL as induction therapy for patients with moderately-severely active UC (CohortA: biologic-naïve, but failed conventional therapy; CohortB: biologic-experienced). Both studies randomized patients 2:2:1 to oncedaily FIL 200mg/FIL 100mg/placebo(PBO). The primary endpoint for both studies was endoscopic/rectal-bleeding/stool-frequency (EBS) remission at Wk10 (definition see [Table]). Key secondary endpoints included Mayo Clinic Score(MCS) remission, endoscopic remission (ES=0), and Geboes histologic remission at Wk10.

Results Baseline demographics, UC disease characteristics and concomitant medications were generally similar across treatment groups and cohorts. CohortA (n = 659) baseline: mean MCS=8.6, 56 % severe endoscopic disease (ES=3). 625(95 %) completed treatment; most common reason for treatment discontinuation was an adverse event (AE). A significantly higher proportion of patients treated with FIL 200mg vs PBO achieved EBS-remission and all key secondary endpoints. CohortB (n = 689) baseline: mean MCS=9.3, 78 % had ES=3. Prior anti-TNF-failure: ≈86 %; prior vedolizumab-failure: 52 %; 43 % had failed both. 635 (92 %) completed treatment; most common reason for treatment discontinuation was an AE. A significantly higher proportion of patients receiving FIL 200mg vs PBO achieved EBS-remission ([Table]).Incidence of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO. In PBO, FIL 100mg and FIL 200mg groups, serious infection occurred in 0.7 %, 0.7 % and 0.4 % of patients in CohortA, and 1.4 %, 1.4 % and 0.8 % in CohortB. Herpes zoster infection occurred in 0 %, 0 % and 0.8 % of patients in CohortA, and 0 %, 0.4 % and 0.4 % in CohortB.

Conclusions The SELECTION study population included a high proportion of dual-refractory patients, and patients with severe endoscopic disease. Both doses of FIL were well tolerated. FIL 200mg was effective as induction treatment for both biologic-naïve and biologic-experienced patients with moderately to severely active UC.

Tab. 1

Efficacy summary for Cohort A and Cohort B

	Cohort A Induction Study (Biologic naïve)				Cohort B Induction Study (Biologic experienced)
	PBO (n = 137)	FIL 100mg (n = 277)	FIL 200mg (n = 245)	∆% FIL 200mg vs PBO (95 % CI); p value	PBO (n = 142)	FIL 100mg (n = 285)	FIL 200mg (n = 262)	∆% FIL 200mg vs PBO (95 % CI); p value
EBS remission, n (%)	21 (15.3)	53 (19.1)	64 (26.1)	10.8(2.1, 19.5); p = 0.0157	6 (4.2)	27 (9.5)	30 (11.5)	7.2 (1.6, 12.8), p = 0.0103
MCS remission, n (%)	17 (12.4)	47 (17.0)	60 (24.5)	12.1 (3.8, 20.4); p = 0.0053	6 (4.2)	17 (6.0)	25 (9.5)	5.3 (−0.1, 10.7); p = 0.0393
Endoscopic remission, n (%)	5 (3.6)	16 (5.8)	30 (12.2)	8.6 (2.9, 14.3); p = 0.0047	3 (2.1)	6 (2.1)	9 (3.4)	1.3 (−2.5, 5.1); p = 0.4269
Geboes histologic remission, n (%)	22 (16.1)	66 (23.8)	86 (35.1)	19.0 (9.9, 28.2); p < 0.0001	12 (8.5)	39 (13.7)	52 (19.8)	11.4 (4.2, 18.6); p = 0.0019

EBS remission=endoscopic subscore ≤1, rectal bleeding subscore=0, and ≥1-pt decrease in stool frequency subscore from baseline and stool frequency subscore ≤1; MCS remission = MCS ≤2 and no single subscore > 1; Endoscopic remission=Mayo endoscopic subscore=0; Geboes histologic remission=Grade 0 of ≤0.3, Grade 1 of ≤1.1, Grade 2a of ≤ 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0.CI, confidence interval; EBS, endoscopy/bleeding/stool; FIL, filgotinib; MCS, Mayo Clinic Score; PBO, placebo

Publication History

Article published online:
01 September 2021