A Clinician’s Update on Infection Risk in Patients Receiving Biologic and Targeted Synthetic DMARDs for Autoimmune Disease

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety.