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DOI: 10.1055/s-0041-1734236
Efficacy and Safety of Filgotinib as Maintenance 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) Maintenance-Study was a double-blind, randomized trial of FIL as maintenance therapy for patients with moderately to severely active UC who achieved clinical remission or Mayo Clinic Score (MCS) response after 10 weeks induction with FIL 200mg, FIL 100mg or placebo (PBO). Patients randomized to FIL induction were rerandomized 2:1 to their induction FIL dose or PBO. Patients randomized to induction PBO continued PBO maintenance. Steroid tapering was mandatory. Primary endpoint was endoscopic/rectal-bleeding/stool-frequency (EBS) remission (definition in [Table]) at Wk58. Key secondary endpoints included 6-month corticosteroid-free clinical remission, sustained clinical remission, MCS remission, endoscopic remission and Geboes histologic remission at Wk58.
Results A total of 664 patients were enrolled and treated (n = 93 PBO, n = 270 FIL 100mg, and n = 301 FIL 200mg; efficacy analyses included only patients who received FIL during induction (n = 558). Baseline demographics were generally balanced across treatment arms; ≈40 % of patients were biologic-experienced.A significantly higher proportion of patients on FIL 200mg or FIL 100mg achieved EBS remission vs PBO. Significantly higher proportions of patients achieved key secondary endpoints with FIL 200mg vs PBO.Incidences of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across treatment arms. Serious infection and herpes zoster infection were infrequent. No opportunistic infections occurred. No venous thromboses, including pulmonary embolism, occurred among FIL-treated patients. Two patients on FIL 200mg died (1 asthma exacerbation, 1 left ventricular failure), both considered unrelated to FIL.
Conclusions FIL 200mg and 100mg were effective as maintenance treatment and well tolerated for patients with moderately to severely active UC who had achieved clinical response to induction treatment with FIL. FIL 200 mg met all key secondary endpoints including endoscopic, histologic and 6-month corticosteroid-free remission.
|
Induction Treatment |
FIL 200mg |
FIL 100mg |
|||
|---|---|---|---|---|---|
|
Maintenance Treatment |
PBO |
FIL 200mg |
PBO |
FIL 100mg |
|
|
EBS remission, n/N (%) |
11/98 (11.2) |
74/199 (37.2)[*] |
12/89 (13.5) |
41/172 (23.8)† |
|
|
6-month corticosteroid-free -clinical remission, n/N (%) |
3/47 (6.4) |
25/92 (27.2)[*] |
2/37 (5.4) |
11/81 (13.6) |
|
|
Sustained clinical remission, n/N (%) |
5/98 (5.1) |
36/199 (18.1)[*] |
7/89 (7.9) |
15/172 (8.7) |
|
|
MCS remission, n/N (%) |
9/98 (9.2) |
69/199 (34.7)[*] |
12/89 (13.5) |
39/172 (22.7) |
|
|
Endoscopic remission, n/N (%) |
6/98 (6.1) |
31/199 (15.6)[*] |
7/89 (7.9) |
23/172 (13.4) |
|
|
Geboes histologic remission, n/N (%) |
13/98 (13.3) |
76/199 (38.2)[*] |
16/89 (18.0) |
48/172 (27.9) |
|
|
Induction Treatment |
PBO |
FIL 200mg |
FIL 100mg |
||
|
Maintenance Treatment |
PBO (n = 93) |
PBO (n = 99) |
FIL 200mg(n = 202) |
PBO(n = 91) |
FIL 100mg(n = 179) |
|
AE, n (%) |
57 (61.3) |
59 (59.6) |
135 (66.8) |
60 (65.9) |
108 (60.3) |
|
Discontinued due to AE, n (%) |
3 (3.2) |
2 (2.0) |
7 (3.5) |
4 (4.4) |
10 (5.6) |
|
Serious AE, n (%) |
4 (4.3) |
0 |
9 (4.5) |
7 (7.7) |
8 (4.5) |
|
Death, n (%) |
0 |
0 |
2 (1.0) |
0 |
0 |
|
Infections, n (%) |
21 (22.6) |
25 (25.3) |
71 (35.1) |
27 (29.7) |
46 (25.7) |
|
Serious infections, n (%) |
1 (1.1) |
0 |
2 (1.0) |
2 (2.2) |
3 (1.7) |
|
Herpes zoster, n (%) |
0 |
0 |
1 (0.5) |
1 (1.1) |
0 |
|
Any venous thrombosis, n (%) |
2 (2.2) |
0 |
0 |
0 |
0 |
|
Any arterial thrombosis, n (%) |
0 |
0 |
0 |
0 |
1 (0.6) |
* p < 0.025, †p < 0.05 FIL dose arm vs PBOEBS remission=ES of 0 or 1, rectal bleeding subscore of 0, and ≥1-point decrease in SFS from baseline to achieve a SFS of 0 or 1; 6-month corticosteroid-free EBS remission =EBS remission with no corticosteroid use for the indication of UC for ≥6 months prior to Wk58 among patients who were on corticosteroids at baseline of maintenance study; Sustained EBS remission=EBS remission at both Wk10 and Wk58; MCS remission=MCS of ≤2 and no single subscore > 1; Endoscopic remission=ES of 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.AE, adverse event; FIL, filgotinib; MCS, Mayo Clinic Score; PBO, placebo
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Publikationsverlauf
Artikel online veröffentlicht:
01. September 2021
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