DOP123Risk of serious infections in patients with inflammatory bowel disease with or without corticosteroid treatment: A nationwide propensity score-matched cohort study

Abstract Background We aimed to assess infection risk in patients with IBD, with or without corticosteroids, across different treatments, since such data are scarce. Methods Using nationwide Swedish registers (2007–2024), we assessed rates of serious and opportunistic infections in patients with IBD, with and without corticosteroids, during exposure periods with different therapies (naïve to immunomodulators/advanced therapies; immunomodulators; and advanced therapies, including TNF inhibitors, vedolizumab, ustekinumab, Janus kinase inhibitors, and risankizumab). For contextualization, we compared these rates to matched (by sex, age, and residence) general population comparators. Within the IBD population, we performed 1:1 propensity score-matching to compare infection rates in patients with or without corticosteroids across strata of concomitant treatment. Propensity scores were estimated using logistic regression including baseline demographics, time since diagnosis, comorbidities, health care utilisation, infections prior to index date, and prior exposure to advanced therapy. Incidence rates (IRs), IR differences, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated. Results We identified 145,125 exposure periods in IBD patients naïve to immunomodulator/advanced therapy, 82,675 on immunomodulators, and 90,181 on advanced therapies. Across therapies, exposure periods with corticosteroids showed higher rates of serious and opportunistic infections than periods without corticosteroids compared to the general population (IR difference range=3.6–10.2/100 person-years; aHR range=4.52–15.86) (Figure 1). The pattern was similar when restricting outcomes to opportunistic infections (data not shown). While hazard ratios were highest in younger patients, incidence rate differences were similar across age groups (data not shown). In propensity score-matched comparisons of exposure periods with or without corticosteroids among patients with IBD on different concomitant treatments, rates were 2-4 times higher during corticosteroid exposure (IR difference range=3.9–8.5/100 person-years; aHR range=1.82–3.60) (Figure 2). Hazard ratios increased with cumulative corticosteroid dose per course (data not shown). Conclusion Patients with IBD receiving corticosteroids had significantly higher rates of serious and opportunistic infections compared with those not receiving corticosteroids across all therapies with important rate differences across age groups and combinations of immunosuppressive treatments. Use of corticosteroids should prompt individualised infection risk stratification and consideration of preventive treatment strategies. Conflict of interest: Forss, Anders: Served as speaker/advisory board member for Janssen Cilag AB and Tillotts Pharma. Axelrad, Jordan: Research grants from BioFire Diagnostics, Genentech, Janssen, and Takeda. Consultancy fees, honorarium, or advisory board fees from Abbvie, Abviax, Adiso, BioFire Diagnostics, Biomerieux, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Pfizer, Sanofi, Takeda, and Vedanta. Söderling, Jonas: Dr. Söderling has worked on projects at Karolinska Institutet and SWIBREG partly financed by grants from Ferring and Janssen. Mårild, Karl: Dr. Mårild is a sub-investigator at a clinical trial financed by Pfizer and have been a speaker at a meeting initiated by Pfizer. Hreinsson, Jóhann P.: Declares no conflicts of interest. Grip, Olof: Dr. Grip has served as speaker and/or advisory board member for AbbVie, Bristol-Myers Squibb, Ferring, Janssen-Cilag, MSD, Pfizer, Takeda, Tillotts Pharma, Vifor Pharma. Halfvarson, Jonas: Grant support: Swedish Foundation for Strategic Research (RB13-0160 to J.H.), the Swedish Research Council (2020-02021 to J.H.), the Örebro University Hospital research foundation (OLL-890291 to J.H.), NordForsk (90569 to J.H.) and Vinnova (2019-01185 to JH and 2024-01155 co-applicant), IHI, EU, INTERCEPT (Grant agreement number 101194780, co-applicant), miGut-Health, HORIZON-HLTH-2022, EU (Grant Agreement 101095470, Co-applicant), 3TR, IMI 2, EU, (Grant agreement number 831434, Co-applicant), Janssen, MSD, and Takeda. Consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Hospira, Index Pharmaceuticals, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB and speaker’s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma and research grant support from Janssen, Merck Sharp & Dohme and Takeda. Naucler, Pontus: Dr. Naucler is PI on a project at Karolinska Institutet financed by Merck. Ludvigsson, Jonas: Dr. Ludvigsson has coordinated an unrelated study on behalf of the Swedish IBD Register (SWIBREG). This study received funding from Janssen corporation. He has also received financial support from Merck/MSD to develop a paper reviewing national healthcare registers in China, and for unrelated IBD research. Ludvigsson receives funding for celiac disease research from Takeda and has ongoing discussions with this company about a collaboration on chronic liver disease research. Olen, Ola: Karolinska Institutet has received research grants from Pfizer, Janssen, AbbVie, Takeda, Ferring, Bristol Myers Squibb, and Alfasigma for projects led by Olén. Ola Olén has also received fees for lectures from Pfizer, Janssen, Bristol Myers Squibb, and Takeda.