Introduction

Persistent high-risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC).
HR-HPV prevalence is higher in men who have sex with men living with HIV (MSMLWH) than in HIV-negative MSM, respectively 74% and 37-41% (1,2). The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP. The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytohistology in MSM using PrEP and MSMLWH. Preliminary data are reported here and final results are expected in coming months.

Aims & Methods

MSM using PrEP and MSMLWH were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing. Patients with HR-HPV infection, abnormal cytology or both were subsequently sent for High Resolution Anoscopy (HRA).

Results

At present, we enrolled 150 MSM using PrEP and 107 MSMLWH. Quality of anal swabs was sufficient in respectively 95% (n=143) and 81% (n=87). HR-HPV prevalence in MSM using PrEP was comparable with HR-HPV prevalence in MSMLWH; respectively 74% (n=106) and 75% (n=65) tested positive for at least one HR-HPV (p=1.000). No significant difference in abnormal cytology was seen; 53% (n=76) of MSM using PrEP and 58% (n=51) of MSMLWH had either ASC-US, ASC-H, LSIL or HSIL (p=0.6). Until today, 58 MSM using PrEP and 31 MSMLWH underwent HRA. Biopsies were performed in 43 MSM using PrEP and 25 MSMLWH. Preliminary results on histology of lesions show presence of anal HSIL in 19% (n=11) and 32% (n=10) respectively (p= 0.706).

Conclusion

MSM using PrEP have a similar risk of HR-HPV infection and abnormal anal cytohistology as MSMLWH, which is higher than what has been reported in HIV-negative MSM not using PrEP (1). ANCHOR showed that treating anal HSIL reduces the incidence of anal SCC in people living with HIV (3), but the risk of progression to anal cancer and thus the need for screening and treatment is to be investigated in this immunocompetent population of MSM using PrEP.

References

1. Wei F, Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
2. Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
3. Palefsky J, Lee J, Jay N et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 202;386(24):2273-82.

Introduction

Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies.

Aims & Methods

Retrospective multicenter study (8 centers) of UC patients who failed ≥1 advanced therapy. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission (fecal calprotectin ≤ 250 µg/g) and endoscopic remission (Mayo Endoscopic Subscore=0). Time to remission was assessed using Cox regression analysis. A subanalysis was performed including only second-line use after anti-TNF failure. Multivariate analysis was performed, adjusted for duration of disease, extent and number of prior therapies.

Results

We evaluated 259 cases [54.4% (n=141) female; diagnostic age 32.3 ± 15.1 years] who initiated UST (n=105; 40.5%), UPA (n=87; 33.6%) or TOFA (n=67; 25.9%). The groups were similar in disease duration (UST: 11.6 ± 8.0; UPA: 9.8 ± 6.4; TOFA: 10.4 ± 5.4 years) and 49.8% (n=129) had failed ≥2 previous AT
At week 16, UPA showed higher SFCR compared to UST (OR 2.1; p=0.014) and TOFA (OR 2.1; p=0.040), with no difference at week 52. Biochemical remission was higher with UPA at week 16 vs UST (OR 2.3; p=0.015) and TOFA (OR 2.1; p=0.039) and at week 52 vs UST (OR 4.7; p=0.010) and TOFA (OR 4.6; p=0.013). At week 16, endoscopic remission was higher with UST (OR 3.5; p=0.036) and UPA (OR 3.1; p=0.041) compared to TOFA; and at week 52, UPA was associated with higher endoscopic remission vs UST (OR 3.6; p=0.036).
In Cox regression, UPA achieved earlier biochemical remission than UST (HR 1.9; p<0.001) and TOFA (HR 1.8; p=0.011). JAK inhibitors led to earlier endoscopic remission than UST (vs UPA: HR 3.2; p<0.001; vs TOFA: HR 1.4; p=0.002).
In the subanalysis, UPA as second-line therapy demonstrated higher SFCR than TOFA (OR 3.6; p=0.035) and higher endoscopic remission at week 52 than TOFA (OR 12.0; p=0.017), and trend-wise compared to UST (OR 4.5; p=0.090).

Conclusion

Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results in this real world study.

References

Singh, Siddharth, et al. "AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis." Gastroenterology 167.7 (2024): 1307-1343.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391

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

References

1. Sands et al. N Engl J Med 2024; 26;391:1119-1129
2. 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.

Introduction

Risankizumab (RZB) is a high-affinity humanised immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to the p19 subunit of the interleukin-23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor.^1,2 Long-term RZB therapy for 3 years of maintenance showed durable efficacy and a well-tolerated safety profile in patients with ulcerative colitis (UC) in the COMMAND open-label extension (OLE) study.^1,3 This post hoc analysis evaluated the long-term efficacy of RZB in improving patient-reported outcomes through week (wk) 96 of the ongoing COMMAND OLE study.

Aims & Methods

COMMAND OLE is a 220-wk study enrolling patients who completed 52-wks maintenance dosing or enrolled directly as responders to induction.^1,3 This analysis included patients who completed 52 wks maintenance and an additional 96 wks of RZB treatment in the OLE. All patients received subcutaneous (SC) RZB180 Q8w starting at OLE wk 0, except patients who had prior rescue therapy (single RZB 1200 mg intravenous dose, then SC RZB360 Q8w) who continued RZB360 in the OLE. The OLE study was not designed to compare RZB180 and RZB360 groups. The data cut-off date for this interim analysis was 30 June 2024. Efficacy outcomes included the percentage of patients who achieved the absence of abdominal pain, bowel urgency, faecal incontinence, nocturnal bowel movements, tenesmus, sleep disruption due to UC symptoms; Inflammatory Bowel Disease Questionnaire (IBDQ) response; a meaningful within-person change (MWPC) in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Short-Form Health Survey-36 version 2 Mental Component Score (SF-36v2 MCS), and SF-36v2 Physical Component Score (PCS). Results were reported using as-observed (AO; Table) and nonresponder imputation (NRI) methods (Table). Safety was reported previously.³

Results

Of the 1003 patients (RZB180 = 701; RZB360 = 302) who entered the OLE, 398 (39.7%) patients (RZB180 = 262; RZB360 = 136) completed wk 96 at data cut-off date. In the AO analysis, RZB180- or RZB360-treated patients showed sustained improvements from OLE wks 0 to 96 in the absence of abdominal pain, bowel urgency, nocturnal bowel movements, tenesmus, faecal incontinence, sleep disruption due to UC symptoms, IBDQ response, MWPC in FACIT-Fatigue, SF-36 PCSv2, and SF-36v2 MCS (Table). Using the more conservative NRI analysis, similar results were observed for most endpoints through OLE wk 96 (Table). Despite RZB360-treated patients were more likely to have numerically higher clinical and endoscopic activity at OLE wk 0 compared with RZB180-treated patients (Adapted Mayo Score [AMS], mean [standard deviation], RZB180, 2.0 [1.4]; RZB360, 3.5 [2.0]; endoscopic subscore: RZB180, 1.1 [1.0]; RZB360, 1.9 [1.0]; clinical remission per AMS, RZB180, 54.8%; RZB360, 24.8%), at OLE wk 96, both RZB dosing regimens exhibited consistent and similar sustained improvements throughout all investigated patient-reported outcomes.

Conclusion

RZB-treated patients who completed OLE wk 96 (3 years of total maintenance therapy) experienced sustained improvement in quality of life and patient-reported outcomes.

References

1. Louis E, et al. JAMA. 2024; 332:881-97.
2. Singh S, et al. mAbs. 2015;7:778-91.
3. Atreya R, et al. J Crohn’s Colitis. 2025;19(S1):i108-i110 [Abstract].

Disclosure

Funding: AbbVie funded this study (COMMAND; NCT03398135) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. 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; S. Michael Austin, of AbbVie, provided editorial support.
Disclosures: Luc Biedermann has received lecture and consulting fees from Takeda, Sanofi, AbbVie, Falk, Bristol Myer Squibb, and Pfizer and is on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Falk, Janssen, Pfizer, Takeda, and Sanofi.
Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.
Silvio Danese has received consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Enthera, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, Lilly, Merck Sharp and Dohme, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor.
Satoshi Tanida received speaker fees from JIMRO, Mitsubishi Tanabe Pharma, AbbVie, Janssen, Kissei, writing fees from Pfizer, and research funding from AbbVie.
Parambir S. Dulai received research support and/or consulting for AbbVie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genentech/Roche, Geneoscopy, Janssen, Pfizer, Takeda.
Nidhi Shukla, Jasmina Kalabic, Pierre Morisset, Cecile Holweg, and Dolly Sharma, are employees of AbbVie and may own stock options.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.