Introduction

Sex-based differences have shown to impact ulcerative colitis (UC) treatment outcomes and need to be considered when managing therapy strategies for patients with UC. Etrasimod is an oral, once‑daily (QD), selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active UC.

Aims & Methods

This pre-defined subgroup analysis reports on efficacy and safety outcomes in male and female patients receiving etrasimod 2 mg QD or placebo in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. Key efficacy endpoints were assessed in patients with a baseline modified Mayo score 5–9 at Week 12 (data pooled from both trials) and Week 52 (ELEVATE UC 52 only). Safety was assessed in the pooled ELEVATE UC 52 and ELEVATE UC 12 safety population.

Results

In the pooled population, a total of 269 male and 227 female patients received etrasimod; 150 and 97, respectively, received placebo. Significantly more male and female patients receiving etrasimod vs placebo achieved clinical remission (Week 12 – male: percentage difference for etrasimod vs placebo [Δ] 10.7, female: Δ 19.7; Week 52 – male: Δ 21.5, female: Δ 29.1; all p < 0.01), symptomatic remission (Week 12 – male: Δ 21.4, female: Δ 20.6; Week 52 – male: Δ 26.4, female: Δ 22.5; all p < 0.01), endoscopic improvement (Week 12 – male: Δ 12.7, female: Δ 21.2; Week 52 – male: Δ 21.9, female: Δ 32.5; all p < 0.01) and endoscopic improvement-histologic remission (Week 12 – male: Δ 9.9, female: Δ 16.7; Week 52 – male: Δ 14.1, female: Δ 24.1; all p < 0.01; Table). Similar findings were seen for corticosteroid‑free and sustained clinical remission (Table). Similar proportions of treatment‑emergent adverse events (TEAEs; 56.8% and 64.6%), serious TEAEs (4.9% and 5.0%) and TEAEs leading to discontinuations (3.8% and 5.8%) were reported in male and female patients receiving etrasimod and were comparable to those receiving placebo.

Conclusion

Similar findings in male and female patients support the use of etrasimod in both to achieve symptomatic, endoscopic and histologic outcomes.

References

Disclaimer: Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

JT receives advisory board fees from AbbVie, Lilly, Janssen and Pfizer Inc; research grants from AbbVie and Janssen; and speaker fees from AbbVie, Janssen, Lilly, Takeda and Pfizer Inc.
RB receives advisory board fees from AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Lilly, Takeda and Pfizer Inc; and consultancy/speaker/moderator fees from AbbVie, Bristol Myers Squibb, Celltrion, Ferring, Janssen, Takeda and Pfizer Inc.
AJY receives consultancy fees from AbbVie, Arena, Bristol Myers Squibb, Celltrion, Pfizer Inc and Takeda; and lecture fees from AbbVie and Bristol Myers Squibb.
MG, EK are employees of Pfizer AG and shareholders of Pfizer Inc.
LH is an employee of Pfizer R&D UK Ltd.
ABD is an employee of Pfizer Inc, Philippines.
KW is an employee of Pfizer Canada Inc and shareholder of Pfizer Inc.
IB reports consulting and lecturer fees from AbbVie, Amgen, Biogen, Janssen‐Cilag, Celgene/BMS GmbH, Celltrion, Falk Foundation, Fresenius Kabi, Galapagos, Lilly,Merck, Pharmacosmos, Pfizer, Takeda, and Tillotts.

Clinical Case Summary

Introduction: Infliximab, an anti-TNF agent, has revolutionized the management of inflammatory bowel disease (IBD), promoting long-term remission and improving quality of life. However, paradoxical immune-mediated reactions, including autoimmune dermatologic conditions, have been increasingly recognized.
Aims & Methods: We report a rare case of paradoxical development of giant pyoderma gangrenosum (PG) in a patient with Crohn’s disease during Infliximab maintenance therapy.
Case Report: A 26-year-old female with Crohn’s disease (A2, L3, B1), in clinical remission under Infliximab, developed a pustular erythematous nodule (~5 cm) on the right popliteal region after the third maintenance dose. The lesion rapidly expanded to a painful ulcerative plaque with inflammatory borders, reaching 15 cm in diameter within 8 days. Histopathology revealed dense neutrophilic dermatosis, confirming pyoderma gangrenosum.
Results: This case exemplifies a paradoxical reaction induced by anti-TNF therapy. Although PG is more commonly associated with ulcerative colitis, it may occur in Crohn’s disease and be exacerbated by immunomodulation. The lesion was managed with corticosteroids and discontinuation of Infliximab, with partial improvement.
Conclusion: Paradoxical PG during anti-TNF therapy is rare but significant. Clinicians should be alert to unusual dermatologic manifestations in IBD patients on biologics. Early recognition and multidisciplinary management are essential to mitigate morbidity.

References

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• Autores: Llamas-Velasco M, García-Diez A, Daudén E.J Crohns Colitis. 2013;7(10):e479-81.
2) Paradoxical skin reactions to anti-TNFα agents: a study of 118 cases.
• Autores: Ramos-Casals M, Brito-Zerón P, Muñoz S, Soto MJ.Br J Dermatol. 2010;163(5):1159-65.
3) Paradoxical psoriasis and pyoderma gangrenosum induced by anti-TNF therapy in inflammatory bowel disease: a case series.
• Autores: Navarini AA, Trüeb RM, Imhof L, French LE.J Crohns Colitis. 2011;5(5):457-62.