Immunosuppressive medication exposure and risk of invasive fungal and nontuberculous mycobacterial infections following TNF-α inhibitor initiation: a time-varying analysis.

Alexander J Ruehman, Shaimaa Elshafie, Mohammed Zuber, Lorenzo Villa Zapata, Andrés F Henao-Martínez, Daniel B Chastain

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Article in Infection, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Alexander J Ruehman *Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, 21201, USA.

Shaimaa Elshafie *Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.ORCID https://orcid.org/0000-0001-7279-4418

Mohammed Zuber *Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.ORCID https://orcid.org/0000-0002-4842-7551

Lorenzo Villa ZapataDepartment of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.ORCID https://orcid.org/0000-0002-3821-4595

Andrés F Henao-MartínezDivision of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.ORCID https://orcid.org/0000-0001-7363-8652

Daniel B ChastainDepartment of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, 914 New Bailie Street HM Bldg, Room 116, Augusta, GA, 30912, USA. daniel.chastain@uga.edu.ORCID https://orcid.org/0000-0002-4018-0195

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6 · The paper itself

Abstract

purposeInvasive fungal and nontuberculous mycobacterial (NTM) infections are important complications following TNF-α inhibitor initiation, but the contribution of additional immunosuppressive medication exposure remains incompletely defined. We evaluated their incidence and spectrum and associations with time-varying immunosuppressive medication exposure.

methodsWe conducted a retrospective cohort study using Merative MarketScan data (2018-2022) among adults initiating TNF-α inhibitors. Invasive fungal and NTM infections were identified using ICD-10-CM codes. Systemic glucocorticoid and non-glucocorticoid immunosuppressant exposures were modeled as time-varying variables. Cox proportional hazards models evaluated associations between immunosuppressive medication exposure and infection risk.

resultsAmong 62,772 adults, 238 (0.4%) developed an invasive fungal or NTM infection after a median of 14.6 months, corresponding to 146 per 100,000 person-years. Histoplasmosis (26%), NTM infections (22%), and coccidioidomycosis (16%) were most common. In time-varying analyses, glucocorticoid exposure alone (aHR 1.77, 95% CI 1.24-2.52) and non-glucocorticoid immunosuppressant exposure alone (aHR 2.25, 95% CI 1.43-3.52) were associated with higher infection risk compared with periods without either exposure. Combined exposure was not associated with infection risk (aHR 1.31, 95% CI 0.92-1.85).

conclusionsInvasive fungal and NTM infections were uncommon following TNF-α inhibitor initiation. Time-varying glucocorticoid and non-glucocorticoid immunosuppressant exposures were associated with higher infection risk, illustrating the importance of dynamic immunosuppressive medication exposure when assessing infection risk during longitudinal care.

Indexed as

AdultCoccidioidomycosisGlucocorticoidsHistoplasmosisImmunosuppression therapyImmunosuppressive agentsOpportunistic infections

Identifiers

PMID42671776

DOI10.1177/20499361251313841

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