Abstract
Aims
SELECTION (NCT02914522) Maintenance evaluated filgotinib (FIL), a preferential JAK1 inhibitor, as maintenance therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who achieved clinical remission or Mayo Clinic Score (MCS) response after 10 weeks of FIL 200mg QD, FIL 100mg QD or placebo (PBO) induction.
Methods
Pts randomized to FIL induction were rerandomized 2:1 to their induction FIL dose or PBO; pts randomized to PBO induction continued PBO maintenance. Steroid tapering was mandatory. The primary endpoint was clinical remission at Week 58. Key secondary endpoints and exploratory endpoints were assessed at Week 58.
Results
664 pts were treated in the Maintenance Study (n=93, 270, and 301 from induction with PBO, FIL 100mg and FIL 200mg); efficacy analyses included only FIL induction pts. Baseline demographics and disease characteristics were generally balanced across treatment arms; 40% were biologic experienced. Significantly higher proportion of pts on FIL 200mg or FIL 100mg were in clinical remission vs PBO. Significantly higher proportions of pts achieved key secondary endpoints with FIL 200mg vs PBO. More pts on FIL 200 mg or FIL 100mg achieved an MCS response and endoscopic improvement vs PBO.
Incidences of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across arms. Serious infection (<2%) and herpes zoster (<1%) were infrequent among FIL-treated patients. There were no venous thromboses, including pulmonary embolism, among FIL-treated pts. Two pts on FIL 200mg died, both AEs leading to death were considered unrelated to FIL.
Conclusions
FIL 200mg and FIL 100mg were effective as maintenance treatment for pts with moderately to severely active UC who had achieved clinical response to FIL induction treatment. FIL 200 mg met all key secondary endpoints including endoscopic, histologic and 6-month corticosteroid-free remission. FIL was well tolerated in pts with moderate to severely active UC.
SELECTION Maintenance Study Summary of Efficacy
| Induction Treatment | FIL 200mg | FIL 100mg | ||
| Maintenance Treatment | PBO | FIL 200mg | PBO | FIL 100mg |
| Clinical 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 (%)a | 3/47 (6.4) | 25/92 (27.2)* | 2/37 (5.4) | 11/81 (13.6) |
| Sustained clinical remission, n/N (%)a | 5/98 (5.1) | 36/199 (18.1)* | 7/89 (7.9) | 15/172 (8.7) |
| MCS remission, n/N (%)a | 9/98 (9.2) | 69/199 (34.7)* | 12/89 (13.5) | 39/172 (22.7) |
| Endoscopic remission, n/N (%)a | 6/98 (6.1) | 31/199 (15.6)* | 7/89 (7.9) | 23/172 (13.4) |
| Histologic remission, n/N (%)a | 13/98 (13.3) | 76/199 (38.2)* | 16/89 (18.0) | 48/172 (27.9) |
| MCS response, n/N (%)b | 32/98 (32.7) | 133/199 (66.8)* | 35/89 (39.3) | 87/172 (50.6) |
| Endoscopic improvement, n/N (%)b | 15/98 (15.3) | 81/199 (40.7)* | 17/89 (19.1) | 46/172 (26.7) |
a Key secondary endpoints; b exploratory endpoints. *p<0.025, †p<0.05 FIL dose arm vs PBO
Clinical 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 clinical remission =clincial 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 clinical remission=clinical 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. MCS response= reduction of 3 or more points in MCS and at least 30% from induction baseline with an accompanying decrease in rectal bleeding subscore of 1 point or more, or an absolute rectal bleeding subscore of 0 or 1; Endoscopic improvement=Mayo endoscopic subscore of 0 or 1.
FIL, filgotinib; MCS, Mayo Clinic Score; PBO, placebo
Funding Agencies
None