Clinical bottom line
Patients receiving emerging anti-IL-17 therapies for autoimmune diseases may have an altered risk profile for infections, including bacterial, mycobacterial, and fungal pathogens. Current evidence suggests that while these agents can increase susceptibility to certain infections, particularly mucocutaneous candidiasis, the overall risk of serious infections appears lower than with older biologics such as anti-TNF agents. Vigilant infection screening and monitoring remain essential, but infection risk stratification and management strategies may need to be tailored specifically to the immunomodulatory effects of anti-IL-17 therapies. This digest summarizes the available evidence and highlights areas requiring further clinical validation.
What the evidence shows
Anti-IL-17 agents, including secukinumab and ixekizumab, represent a newer class of biologics targeting the IL-17 pathway, which plays a critical role in host defense against extracellular bacteria and fungi. Unlike anti-TNF therapies, which broadly impair immune responses, anti-IL-17 therapies selectively modulate neutrophil recruitment and mucosal immunity (Chatenoud et al., 2006). This mechanistic distinction underpins differences in infectious risk profiles observed in clinical practice.
Data from the Emerging Infections Network and other surveillance cohorts for biologics primarily focus on anti-TNF agents but provide a useful comparative framework. Winthrop et al. (2008) documented increased rates of mycobacterial and serious bacterial infections with anti-TNF therapy, highlighting the need for tuberculosis screening and vigilance. Although direct large-scale epidemiologic data on anti-IL-17 therapies are limited, clinical trial extensions and post-marketing surveillance indicate a lower incidence of serious infections compared to anti-TNF agents, but a notable increase in mucocutaneous candidiasis cases (Winthrop et al., 2008; Chatenoud et al., 2006).
Pulmonary bacterial infections remain a concern in systemic autoimmune disease patients, especially those with underlying lung involvement or receiving concomitant immunosuppressants (Handbook of Systemic Autoimmune Diseases, 2020). Anti-IL-17 therapy’s impact on pulmonary infection risk is less well characterized but warrants caution given IL-17’s role in neutrophil-mediated lung defense (Handbook of Systemic Autoimmune Diseases, 2020).
Fungal infections, particularly invasive candidiasis, have been reported more frequently in patients on anti-IL-17 agents compared to other biologics (Handbook of Systemic Autoimmune Diseases, 2020). This aligns with IL-17’s importance in mucosal antifungal immunity. However, invasive fungal disease rates remain low overall, and serious fungal infections are uncommon outside of additional risk factors such as corticosteroid use or neutropenia.
Risk factors for infection in autoimmune disease patients on biologics are multifactorial. Besada et al. (2016) showed that traditional risk factors and adverse event histories poorly predict infection risk in rituximab-treated granulomatosis with polyangiitis, underscoring the complexity of infection risk stratification. Similar challenges likely apply to anti-IL-17 therapies, necessitating individualized assessment.
Caveats and uncertainty
The evidence base for infection risk with anti-IL-17 therapies is still evolving. Most data derive from clinical trials with selected populations and limited long-term follow-up, potentially underestimating rare or late-onset infections. Real-world registries and pharmacovigilance data remain sparse compared to anti-TNF agents.
Comparative infection risk assessments are complicated by differences in patient populations, concomitant immunosuppressive regimens, and underlying disease severity. The relative contribution of anti-IL-17 therapy versus other immunomodulators to infection risk is often unclear.
Mechanistic understanding of IL-17’s role in host defense is primarily from preclinical and translational studies; clinical correlates require further validation. The impact of anti-IL-17 therapy on latent infections such as tuberculosis is not well defined, though current data suggest a lower risk than anti-TNF agents (Winthrop et al., 2008).
Finally, infection prevention strategies specific to anti-IL-17 therapy have not been standardized. Optimal screening, prophylaxis, and monitoring protocols remain to be established.
How this may change practice
Clinicians managing patients on anti-IL-17 therapies should maintain a high index of suspicion for mucocutaneous candidiasis and other fungal infections and consider early antifungal treatment when indicated. Routine screening for latent tuberculosis remains prudent, although the risk appears lower than with anti-TNF agents.
Individualized infection risk assessment should incorporate patient comorbidities, concomitant immunosuppression, and disease activity. Multidisciplinary collaboration with infectious disease specialists can optimize management, especially for patients with prior serious infections or complex autoimmune disease.
Further real-world data collection and prospective studies are needed to refine infection risk stratification and develop evidence-based guidelines tailored to anti-IL-17 therapies. Until then, clinicians should apply cautious monitoring and patient education regarding infection signs.