Introduction
Risankizumab (RZB), a monoclonal antibody targeting the interleukin-23 p19 subunit, has previously demonstrated improvement in clinical and endoscopic outcomes during induction (INSPIRE) and maintenance (COMMAND) studies in patients with moderate to severe ulcerative colitis (UC).1 Long-term RZB therapy for 1 year (yr) of maintenance followed by 2 years in the COMMAND Open-label extension (OLE) study showed durable efficacy and a well-tolerated safety profile through OLE week (wk) 96.2,3 This post hoc analysis of the ongoing COMMAND OLE study evaluated the durability of clinical and endoscopic outcomes at wks 0 and 96 stratified by the number of prior AT exposure ( 0, 1, >1).
Aims & Methods
The COMMAND OLE enrolled RZB-treated patients who completed the 52-wk maintenance substudies and/or responded to 12/24-wk induction therapy and received at least 1 dose of RZB during the OLE, following up to 3 yrs of RZB treatment (1 yr in the 52-wk maintenance study; 2 yrs of RZB treatment in the OLE [3 yrs total]).2,3 All patients who received RZB rescue therapy (a single RZB 1200 mg intravenous dose, then subcutaneous [SC] RZB 360 mg [RZB360] every 8 wks) prior to OLE wk 0 continued to receive RZB360 every 8 wks during the OLE. All other patients received RZB 180 mg SC (RZB180) every 8 wks during the OLE. Clinical remission (CR) per Adapted Mayo Score (AMS) or Partial Adapted Mayo Score (PAMS), endoscopic improvement, and endoscopic remission were assessed at OLE wks 0 and 96 by the number of prior AT exposures (0, 1, >1). Results were reported using both the as-observed (AO) method prior to RZB rescue therapy during OLE and the modified-nonresponder imputation (mNRI) method (Table). Safety was reported previously.2,3
Results
At induction baseline, among the 1003 patients included in the AO analysis, 29.4% (N = 295) were AT-naïve; 29.4% (N = 295) and 41.2% (N = 418) had previously experienced 1 and > 1 AT, respectively (Table). Among the RZB180 and RZB360 groups, rates of CR (per AMS or PAMS) generally remained stable at OLE wks 0 and 96, regardless of the number of prior AT exposures, per AO analysis. Rates of endoscopic improvement and endoscopic remission were sustained, regardless of the number of prior AT exposures, per AO analysis (Table). Across most endpoints, responses were numerically higher among AT-naïve patients, followed by those with prior exposure to 1 AT, and then by those with prior exposure to >1 AT; however, some responses among AT-exposed approached those observed in AT-naive patients (Table). Similar results were observed for most endpoints at OLE wks 0 and 96 using the more conservative mNRI analysis (Table).
| Endpoint, (n/N) % | No. of prior ATa | RZB 180 mg SC | RZB 360 mg SC |
| AOb | mNRIc | AOb | mNRIc |
| Wk 0 | Wk 96 | Wk 0 | Wk 96 | Wk 0 | Wk 96 | Wk 0 | Wk 96 |
Clinical remission
per AMSd | 0
1
>1 | (138/229)60.3
(127/218)58.3
(119/254) 46.9 | (114/156)73.1
(101/163)62.0
(95/176)54.0 | (118/193)61.1
(122/208)58.7
(117/248)47.2 | (118/193)61.1
(109/208)52.4
(103/248)41.4 | (20/66)30.3
(14/77)18.2
(42/159)26.4 | (21/39)53.8
(20/48)41.7
(44/92)47.8 | (18/56)32.1
(14/71)19.7
(37/150)24.7 | (24/56)42.1
(21/71)29.7
(47/150)31.1 |
Clinical remission
per PAMSe | 0
1
>1 | (182/229)79.5
(170/218)78.0
(179/254)70.5 | (133/152)87.5
(131/167)78.4
(128/166)77.1 | (155/193)80.3
(163/208)78.4
(175/248)70.6 | (133/193)69.0
(131/208)63.0
(128/248)51.8 | (38/66)57.6
(33/77)42.9
(82/159)51.6 | (30/38)78.9
(25/41)61.0
(61/82)74.4 | (32/56)57.1
(30/71)42.3
(74/150)49.3 | (30/56)52.7
(25/71)35.1
(61/150)40.7 |
| Endoscopic improvementf | 0
1
>1 | (164/229)71.6
(152/218)69.7
(152/254)59.8 | (127/159)79.9
(126/162)77.8
(117/178)65.7 | (138/193)71.5
(144/208)69.2
(149/248)60.1 | (145/193)75.0
(144/208)69.3
(149/248)59.9 | (26/66)39.4
(23/77)29.9
(50/159)31.4 | (25/40)62.5
(25/46)54.3
(54/90)60.0 | (22/56)39.3
(22/71)31.0
(45/150)30.0 | (30/56)54.4
(29/71)41.0
(64/150)42.8 |
| Endoscopic remissiong | 0
1
>1 | (95/229)41.5
(72/218)33.0
(62/254)24.4 | (85/159)53.5
(68/162)42.0
(69/178)38.8 | (78/193)40.4
(70/208)33.7
(61/248)24.6 | (93/193)48.1
(77/208)36.8
(82/248)32.9 | (8/66)12.1
(5/77)6.5
(26/159)16.4 | (16/40)40.0
(13/46)28.3
(26/90)28.9 | (6/56)10.7
(5/71)7.0
(23/150)15.3 | (19/56)33.2
(15/71)20.8
(29/150)19.3 |
Table. Efficacy Analysis From the COMMAND Open-Label Extension Study by Number of Prior Advanced Therapies Exposures
AMS, Adapted Mayo Score; AO, as-observed; AT, advanced therapy; IV, intravenous; mNRI, modified-nonresponder imputation; no, number; OLE, open-label extension; PAMS, Partial Adapted Mayo Score; Q8w, every 8 weeks; RBS, rectal bleeding score; RZB, risankizumab; SC, subcutaneous; SFS, stool frequency score; UC, ulcerative colitis; wk, week; yr, year.
Efficacy analysis included patients who entered the OLE from induction or the 52-wk maintenance study and received at least 1 dose of study drug. Analysis included patients who received RZB 180 mg starting at OLE wk 0 and patients who had prior rescue therapy (a single RZB 1200 mg IV dose, then 360 mg SC Q8w) during induction or the 52-wk maintenance study and continued with RZB 360 mg in OLE. The data cut-off date was 25 Aug 2025. Wk 0 was defined as the entry of the OLE period, based on the last nonmissing value prior to the first dose of study drug in the OLE. No statistical comparisons were made.
aIncludes approved biologics for UC (infliximab, adalimumab, golimumab, ustekinumab, and/or vedolizumab), approved Janus kinase inhibitors for UC (tofacitinib, filgotinib, upadacitinib), and/or ozanimod.
bIncludes all patients from the pivotal maintenance study and the exploratory maintenance substudy who received at least 1 dose of study drug in COMMAND OLE, excluding those who received rescue therapy, regardless of whether they completed wk 96. AO analysis does not impute values for missing data.
cIncludes all patients enrolled from the pivotal maintenance study and exploratory maintenance substudy, who received at least one dose of study drug in the COMMAND OLE and completed up to 3 yrs of total RZB therapy (2 yr in the OLE in addition to 1 yr in the pivotal maintenance study).
dDefined as SFS ≤ 1, and not greater than baseline, RBS = 0, and endoscopic subscore ≤ 1 without evidence of friability.
eDefined as SFS ≤ 1, and not greater than baseline, and RBS = 0.
fDefined as an endoscopy subscore of 0 or 1 without evidence of friability.
gDefined as endoscopic subscore = 0. |
Conclusion
Patients who received up to 3 yrs of long-term RZB maintenance treatment demonstrated durable improvements, with high response rates among AT-naïve patients at OLE wk 96. Although responses were generally the highest among AT-naïve patients, patients with prior AT exposure also showed sustained improvement over time.
References
- Louis E, et al. JAMA. 2024;332:881-97.
- Panaccione R, et al. J Crohns Colitis. 2025;19(1), jjaf005.
- Atreya R, et al. J Crohn’s Colitis. 2026;20(S1):i231-33 [abstract].
Disclosure
Funding: AbbVie funded this study (COMMAND; NCT03398135) and participated in the study design, research, analysis, data collection, data interpretation, review, and publication approval. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.
Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support; Catherine Barone, PhD, of AbbVie, provided editorial support.
Joanna Torres has received consulting/advisory board fees from AbbVie, Pfizer, Janssen, Takeda, Sandoz, and Lilly, as well as grant support from Janssen and AbbVie.
Mark Samaan has served as a speaker, a consultant and/or an advisory board member for AbbVie, Bristol Myers Squibb, Sandoz, Janssen, Takeda, MSD, Falk, and Samsung Bioepis.
Brigid S. Boland has received research grants from Prometheus Biosciences, Merck, Mirador, SRT Therapeutics, and Gilead; served on advisory boards Merck, Celltrion, Abbvie, Sanofi, Jannsen.
Gil Melmed is a consultant for AbbVie, Arena, Boeringer-Ingelheim, Bristol Myers Squibb, Cristcot, Diasorin, Dieta, Ferring, Fresenius Kalbi, Genentech, Gilead, Iterative Scopes, Janssen, Lilly, Merck, Oshi Health, Pfizer, Prometheus Labs, Samsung Bioepis, Takeda, Techlab, Verantos and Viatris. He has received research grants from Pfizer. He has received speaking fees from Abbvie and Janssen.
Colla Cunneen, Daniel O’Brien, Jasmina Kalabic, Nurbek Mambetsariev, and Xiao Li, are employees of AbbVie and may own stocks or stock options.
Marc Ferrante has received research grants from AbbVie, Celltrion, EG Pharma, Janssen, Pfizer, Takeda, and Viatris; consulting fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Numab Therapeutics AG, Pfizer, Takeda, Thermo Fisher, and ZipBio; and speaker fees from AbbVie, Biogen, Boehringer Ingelheim, Dr. Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare, and Viatris.
