Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry

Steven H Itzkowitz; Yue Jiang; Cristina Villagra; Jean-Frederic Colombel; Keith Sultan; Dana J Lukin; David M Faleck; Ellen Scherl; Shannon Chang; LeaAnn Chen; Seymour Katz; Joann Kwah; Arun Swaminath; Francesca Petralia; Virginia Sharpless; David Sachar; Lina Jandorf; Jordan E Axelrad; New York Crohn’s and Colitis Organization

doi:10.1016/j.cgh.2024.05.006

Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry

Clin Gastroenterol Hepatol. 2024 May 18:S1542-3565(24)00479-8. doi: 10.1016/j.cgh.2024.05.006. Online ahead of print.

Authors

Steven H Itzkowitz¹, Yue Jiang², Cristina Villagra³, Jean-Frederic Colombel⁴, Keith Sultan⁵, Dana J Lukin⁶, David M Faleck⁷, Ellen Scherl⁶, Shannon Chang⁸, LeaAnn Chen⁹, Seymour Katz⁸, Joann Kwah⁸, Arun Swaminath¹⁰, Francesca Petralia¹¹, Virginia Sharpless¹², David Sachar⁴, Lina Jandorf¹³, Jordan E Axelrad⁸; New York Crohn’s and Colitis Organization

Affiliations

¹ Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: steven.itzkowitz@mountsinai.org.
² Department of Statistical Science, Duke University, Durham, North Carolina.
³ Department of Population Health, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
⁵ Division of Gastroenterology, Department of Medicine, Northwell Health-North Shore University Hospital, Zucker School of Medicine, Manhasset, New York.
⁶ Division of Gastroenterology, Department of Medicine, Weill Cornell Medicine, New York, New York.
⁷ Gastroenterology, Hepatology and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
⁸ Division of Gastroenterology, Department of Medicine, New York University Grossman School of Medicine, New York, New York.
⁹ Division of Gastroenterology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
¹⁰ Division of Gastroenterology, Department of Medicine, Northwell Health-Lenox Hill Hospital, Zucker School of Medicine, New York, New York.
¹¹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
¹² Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina.
¹³ Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Population Health, Icahn School of Medicine at Mount Sinai, New York, New York.

PMID: 38768673
DOI: 10.1016/j.cgh.2024.05.006

Abstract

Background & aims: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue.

Methods: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications.

Results: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class.

Conclusions: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

Keywords: Crohn’s Disease; Immunosuppression; Incident Cancer; Ulcerative Colitis.