Introduction
Tulisokibart is a monoclonal antibody that targets tumor necrosis factor-like cytokine 1A (TL1A), a regulator of inflammation and fibrosis in inflammatory bowel disorders. In the Phase 2 ARTEMIS-UC study, a significantly higher proportion of participants on tulisokibart compared to placebo achieved clinical remission after 12 weeks of induction treatment in patients with moderate to severe active ulcerative colitis (UC) and conventional or advanced treatment failure.1 In a post hoc analysis from ARTEMIS-UC, re-induction and delayed induction treatment with tulisokibart were effective in participants who did not respond during the initial induction period.2 We explored the efficacy and safety of tulisokibart maintenance therapy up to 1 year during the open-label extension of ARTEMIS-UC among patients who responded to induction, re-induction, and delayed induction.
Aims & Methods
Participants (≥18 years) were randomized to intravenous (IV) tulisokibart 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10 or placebo. The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this analysis. Participants were classified as induction responders (defined as reduction of ≥2 points and ≥30% in modified Mayo score from baseline, accompanied by a reduction ≥1 in rectal bleeding subscore or absolute rectal bleeding subscore ≤1 at week 12) or induction nonresponders. Induction non-responders in the tulisokibart and placebo groups were assigned to an open label 12-week re-induction with the aforementioned tulikosibart induction dosing regimen. Cohort 1 induction, re-induction, and delayed induction responders were randomized (stratified by Dx status) to open-label IV tulisokibart 100 mg or 250 mg every 4 weeks.
Results
In Cohort 1, 47 tulisokibart induction responders, 13 re-induction responders, and 29 delayed induction responders were randomized to open-label maintenance treatment with tulisokibart 100 mg or 250 mg every 4 weeks. Maintenance of treatment effect was generally similar with a trend for higher efficacy with tulisokibart 250 mg vs 100 mg maintenance treatment observed across the 3 groups. The safety profile of tulisokibart maintenance treatment was similar across the 3 groups, with no new safety signals being observed.
Conclusion
Tulisokibart was effective as a maintenance treatment in patients with moderate to severe UC. The effect was generally similar across Cohort 1 tulisokibart induction responders, re-induction responders, and delayed induction responders. Tulisokibart maintenance treatment was well tolerated across the 3 groups, with no identified safety signals. Altogether, this suggests that a second induction regimen in tulisokibart non-responders may result in a long-term efficacy benefit without increased safety risk. Larger trials are needed to confirm these findings.
Table: Efficacy and fecal calprotectin
| As observed | Tulisokibart induction
| Tulisokibart induction responders
| Tulisokibart induction non-responders who responded to re-induction with tulisokibart
| Placebo induction non-responders who responded to delayed induction with tulisokibart
|
Week 12
| Week 34
| Week 50 | Week 26 | Week 48 | Week 26 | Week 48 |
| 100 mg | 250 mg | 100 mg | 250 mg | 100 mg | 250 mg | 100 mg | 250 mg |
Endoscopic improvement, n/N (%)
| 25/68 (36.8)
| N/A
| N/A
| 8/22 (36.4)
| 12/25 (48.0)
| N/A
| 3/6 (50.0)
| 1/7 (14.3)
| N/A
| 4/17 (23.5)
| 3/12 (25.0)
|
Clinical response, n/N (%)
| 45/68 (66.2)
| N/A
| N/A
| 13/22 (59.1)
| 17/25 (68.0)
| N/A
| 3/6 (50.0)
| 4/7 (57.1)
| N/A
| 7/17 (41.2)
| 6/12 (50.0)
|
Symptomatic response, n/N (%)
| 60/68 (88.2)
| 17/22 (77.3)
| 23/25 (92.0)
| 15/22 (68.2)
| 22/25 (88.0)
| 13/21 (61.9)
| 4/6 (66.7)
| 5/7 (71.4)
| 31/41 (75.6)
| 11/17 (64.7)
| 10/12 (83.3)
|
Symptomatic improvement, n/N (%)
| N/A
| 17/22 (77.3)
| 21/25 (84.0)
| 15/22 (68.2)
| 20/25 (80.0)
| 10/21 (47.6)
| 3/6 (50.0)
| 5/7 (71.4)
| 26/41 (63.4)
| 11/17 (64.7)
| 9/12 (75.0)
|
Mean (SD) fecal calprotectin, µg/g
Baseline
Timepoint
|
1219.1
(1381.5)
N=67
594.4
(926.9)
n=55
|
1103.9
(855.7)
n=22
628.5
(995.2)
n=13
|
1204.2
(1614.9)
n=24
239.2
(367.7)
n=19
|
1103.9
(855.7)
n=22
785.0
(1270.5)
n=13
|
1204.2
(1614.9)
n=24
636.7
(916.1)
n=18
|
1228.9
(1548.3)
n=21
906.3
(936.8)
n=18
|
531.7
(565.0)
n=6
791.8
(1473.2)
n=4
|
1377.9
(1075.4)
n=7
399.8
(280.2)
n=4
|
1230.4
(1209.3)
N=41
691.4
(902.6)
n=36
|
877.9
(934.9)
n=17
476.2
(837.5)
n=12
|
1671.9
(1481.4)
n=12
594.5
(968.4)
N=10
|
GM fecal calprotectin fold change from baseline
| 0.21 | 0.30 | 0.21 | 0.31 | 0.23 | 0.48 | 0.22 | 0.25 | 0.41 | 0.47 | 0.17 |
Endoscopic improvement is defined as endoscopy subscore ≤ 1 with no friability.
The 3-component Modified Mayo Score clinical response is defined as reduction from baseline ≥ 2 points and ≥ 30% in 3-component Modified Mayo Score, accompanied by a reduction ≥ 1 in RB subscore or absolute RB subscore ≤ 1.
Symptomatic response is defined as a reduction of PRO-2 score ≥ 1 point from baseline.
Symptomatic improvement is defined as RB subscore = 0 or SF subscore = 0 or 1 with a reduction of ≥ 1 point from baseline.
GM, geometric mean; N/A, not assessed at that timepoint. |
References
- Sands et al. N Engl J Med 2024; 26;391:1119-1129
- Hoque et al. J Crohns Colitis 2025; 19(suppl 1):i1158-i1159
Disclosure
Sami Hoque: Received Lecture fees and research grants from Tillotts, Ferring and Eli Lilly.
Bruce E. Sands: Travel fees from Eli Lilly and Company, Janssen Research & Development, LLC, Takeda Development Center Americas, Inc.; Received food & beverage from AnX Robotica Corp.; Grant from Janssen Research & Development, LLC; Owns stock options in Ventyx Biosciences; Consulting fees from AbbVie, Abivax, Aclaris Therapeutics, Adiso Therapeutics, Agomab Therapeutics, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb Company, Celltrion Healthcare, Celltrion Healthcare, Connect Biopharm, Cytoki Pharma, Eli Lilly and Company, Entera, Enveda Biosciences, Equilium, Evommune, F. Homann-La Roche AG, Ferring, Fresenius Kabi USA, LLC, Galapagos, Genentech USA, Inc., Gilead Sciences , GlaxoSmithKline, GossamerBio, HMP Acquisition, Imhotex, Immunic, Immunyx Pharma Ltd., Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen Biotech, Inc., Janssen Scientific Affairs, LLC, Johnson & Johnson Health Care Systems Inc., Kaleido, Kallyope, Kyowa Kirin Co., Ltd, Merck & Co., Inc., Microba, Microbiotica Limited, MiroBio, Mobius Care, Morphic Therapeutic, MRM Health, Nexus Therapeutics, Nimbus Therapeutics, Odyssey Therapeutics, Pfizer, Progenity Inc., Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Recludix Pharma, SANOFI US SERVICES INC., Spyre Therapeutics, Surrozen, Synlogic Operating Company, Takeda Pharmaceuticals International, Inc., Target RWE, Teva Branded Pharmaceutical Products R&D, Theravance Biopharma Inc., TLL Pharmaceutical, VectivBio AG, Ventyx Biosciences
Brian G. Feagan: Consulting fees from Abbvie, Adiso Therapeutics, Agomab, Alimentiv Inc, Allianthera, Amgen Canada, AnaptysBio, Applied Molecular Transport, Arena Pharma, Biora Therapeutics, Blackbird Laboratories, Boehringer Ingelheim AB, Bristol-Myers Squibb, Celgene, Celsius Therapeutics, Connect BioPharma, Duality, Eli Lilly and Company, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen Global Services, LLC, JapanTobacco, Klick Health, Mage Biologics, Mestag Therapeutics, Mobius Therapeutics, LLC, Monte Rosa Therapeutics, Nexys Therapeutics, Nimbus Discovery Inc, Orphagen Inc., PFIZER CANADA INC, Prometheus, SANOFI US SERVICES INC., Seres Therapeutics, Sobi, Inc, Spyre Therapeutics, Surrozen, Synedgen, Takeda Canada, Takeda Development Center Americas, Inc., Televant, Tillotts, Triastek Inc.
Mark Yen: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Bin Dong: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Wen Zhou: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Silvio Danese: Consulting fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion Healthcare, Ferring, Gilead Sciences, Hospira, Inc., Janssen Biotech, Johnson & Johnson Health Care Systems Inc., Pfizer, Sandoz, UCB Inc., Vifor (International) Ltd.
