A Clinician's Guide to Opportunistic Infections in the Era of Biologic and Targeted Synthetic DMARDs

Background: Immunomodulatory therapies, including biologics, JAK inhibitors, immune checkpoint inhibitors (ICIs), and bispecific antibodies (BsAbs), have reshaped the treatment of autoimmune diseases and malignancies. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: I conducted a scoping review of recent literature to characterize infectious complications associated with modern immunomodulatory drugs, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, I systematically searched 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. After screening 1,046 unique records, 24 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. In oncology, bispecific antibodies have a high incidence of severe infections, driven by neutropenia and hypogammaglobulinemia. Immune checkpoint inhibitors were associated with a 26.9% serious infection rate, with complications difficult to distinguish from immune-related adverse events. Conclusion: The infectious risk associated with modern immunomodulators is not one profile, but a spectrum of specific vulnerabilities. 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.