In modern dermatology, systemic psoriasis therapies have revolutionized the management of chronic, moderate-to-severe plaque psoriasis and associated psoriatic arthritis. However, modulating specific inflammatory cytokine cascades invariably impacts host immune defenses. Consequently, infection-related adverse events represent a vital safety consideration during clinical drug selection. A comprehensive pharmacovigilance study recently evaluated post-marketing safety data from the FDA Adverse Event Reporting System to understand how distinct therapeutic classes influence infection reporting.

Evaluating Infection Risks in Systemic Psoriasis Therapies

Dermatologists frequently weigh clinical clearance against infectious risks when prescribing targeted biologic and nonbiologic agents. Because moderate-to-severe plaque psoriasis requires prolonged therapeutic maintenance, real-world post-marketing registries provide essential safety data beyond randomized controlled trials. Therefore, researchers conducted a disproportionality analysis using FAERS records submitted between the third quarter of 2014 and the third quarter of 2025. The investigation assessed 357,728 psoriasis-indicated reports to quantify infectious event signals across sixteen distinct systemic agents. Specifically, the authors categorized treatments into tumor necrosis factor inhibitors, interleukin-12/23 inhibitors, interleukin-17 inhibitors, interleukin-23 inhibitors, and conventional nonbiologics. Among all submitted safety reports, 67,827 cases contained at least one recognized infection term. The investigators calculated reporting odds ratios and lower bounds of the information component to detect meaningful disproportionality signals. Through this comprehensive approach, the authors revealed substantial disparities in reporting frequency across mechanism classes. These findings offer practical benchmarks for physicians selecting long-term systemic regimens for vulnerable patient populations.

Mechanism-Specific Reporting Patterns in the FAERS Database

The pharmacovigilance analysis uncovered divergent safety signals that closely reflected the biological mechanism of each therapeutic category. In the unadjusted primary analysis, immunosuppressive nonbiologics generated the highest disproportionality signal, yielding a reporting odds ratio of 2.51. Similarly, interleukin-12/23 inhibition demonstrated an elevated reporting odds ratio of 2.43. Furthermore, interleukin-17 inhibitors produced a distinct safety signal with a reporting odds ratio of 1.82. In contrast, tumor necrosis factor inhibitors demonstrated only a modest reporting odds ratio of 1.17. Most notably, selective interleukin-23 inhibitors showed a near-null reporting signal, recording a reporting odds ratio of 0.99 and a negative information component lower bound. Consequently, these numerical contrasts underscore biological differences in immune surveillance disruption. While targeted IL-23 inhibition preserves critical mucosal barrier immunity, dual IL-12/23 inhibition disrupts interferon-gamma pathways essential for intracellular pathogen control. Therefore, clinicians can utilize these comparative metrics to stratify infectious susceptibility before initiating targeted biologic therapy.

Impact of Indication Linkage and Confounding by Indication

Spontaneous reporting registries frequently suffer from reporting bias, polypharmacy, and co-morbid confounding. To address these potential distortions, the study investigators performed a rigorous sensitivity analysis requiring direct drug-sequence linkage to psoriatic disease. Interestingly, this indication linkage materially altered the observed signal for immunosuppressive nonbiologics. The adjusted analysis attenuated the reporting odds ratio for oral immunosuppressive nonbiologics from 2.51 down to 1.14. This significant reduction suggests that multi-indication exposure and off-label usage previously inflated baseline adverse reporting for conventional agents like methotrexate and cyclosporine. In contrast, the elevated infection signals for interleukin-12/23 inhibitors and interleukin-17 inhibitors persisted even after enforcing strict disease linkage. Hence, researchers demonstrated that methodological refinement is vital when evaluating spontaneous reporting databases. Clinicians must interpret raw safety notifications with caution, recognizing that unadjusted pharmacovigilance data may exaggerate conventional drug toxicities. Ultimately, adjusting for true therapeutic indication clarifies authentic biological risks versus observational reporting artifacts.

Candida Risk and Pathophysiological Profiles of IL-17 Inhibitors

A granular evaluation of infectious subtypes revealed unique pathogen-specific liabilities across targeted biologic classes. Most prominently, interleukin-17 inhibitors demonstrated an exceptional disproportionality signal for Candida infections, with a reporting odds ratio of 8.67. This pronounced signal directly reflects the fundamental immunological role of interleukin-17 in mucocutaneous defense. Because interleukin-17 stimulates epithelial production of antimicrobial peptides and mobilizes neutrophils, neutralizing this cytokine pathway impairs protective barrier responses against fungal commensals. As a result, patients receiving secukinumab, ixekizumab, or bimekizumab experience higher rates of oral, esophageal, and vulvovaginal candidiasis. Fortunately, most reported fungal infections remain localized, mild to moderate in severity, and responsive to standard oral antifungals. Nonetheless, clinicians must conduct baseline oral and mucosal examinations prior to commencing interleukin-17 blockade. In addition, healthcare providers should educate patients on recognizing early thrush symptoms to prevent extensive infection and unnecessary drug discontinuation.

Clinical Implications for Practice in Infection-Endemic Regions

These pharmacovigilance findings carry profound clinical relevance for dermatologists and rheumatologists managing psoriatic disease in high-burden environments. In regions where tuberculosis, fungal pathogens, and viral hepatitis remain endemic, selecting appropriate systemic therapies requires vigilant risk mitigation. For example, the near-null infection signal observed with selective interleukin-23 inhibitors offers clinical reassurance for patients with significant infectious comorbidities or advanced age. Conversely, the persistent signals observed with interleukin-12/23 and interleukin-17 inhibitors emphasize the need for vigilant clinical surveillance throughout therapy. Physicians must ensure comprehensive baseline screening, including tuberculin skin tests, interferon-gamma release assays, viral serologies, and chest radiography. Furthermore, practicing physicians should maintain active post-prescription monitoring protocols during routine clinic visits. When managing patients with recurrent fungal infections or latent mycobacterial exposure, tailored mechanism selection substantially optimizes outcomes. Ultimately, combining robust pharmacovigilance data with structured clinical screening protocols ensures safe, efficacious long-term disease control.

Frequently Asked Questions

What did the FAERS analysis reveal regarding the infection safety of IL-23 inhibitors?

The FAERS analysis revealed that selective interleukin-23 inhibitors demonstrated a near-null reporting signal for infection-related adverse events, recording a reporting odds ratio of 0.99. Unlike broader immunosuppressants or dual cytokine inhibitors, selective interleukin-23 blockers preserve fundamental interleukin-17-mediated epithelial barrier defenses and interferon-driven antimicrobial activity. Consequently, interleukin-23 inhibitors present an exceptionally favorable infectious safety profile in real-world pharmacovigilance, offering clinicians a reassuring therapeutic option for infection-vulnerable psoriatic patients.

Why did the infection signal for immunosuppressive nonbiologics attenuate after indication linkage?

The initial elevated infection signal for conventional immunosuppressive nonbiologics dropped from 2.51 to 1.14 after researchers linked drug sequences strictly to psoriatic disease. Conventional immunosuppressants like cyclosporine and methotrexate are widely prescribed across severe autoimmune and transplant indications involving profound baseline immunosuppression. Therefore, unadjusted pharmacovigilance reports captured confounding secondary infections originating from other clinical disorders. Enforcing strict disease-indication linkage effectively removed non-psoriatic confounding, providing an accurate, clinically realistic assessment of infection risks.

How should clinicians approach fungal risk when prescribing IL-17 inhibitors?

Because interleukin-17 inhibitors demonstrated a high reporting odds ratio of 8.67 for Candida infections, clinicians should actively screen mucosal tissues before and during therapy. Interleukin-17 governs mucocutaneous defense by driving neutrophil recruitment and inducing antimicrobial peptides. Clinicians must advise patients regarding common oral thrush or genital candidiasis symptoms. When fungal infections emerge, practitioners can typically manage them using prompt oral antifungals like fluconazole without permanently discontinuing the biologic therapy unless infections become recalcitrant.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice, diagnosis, or treatment. Healthcare professionals should exercise their independent clinical judgment when making treatment decisions. Patient details and clinical scenarios have been anonymized or adapted where applicable. While every effort is made to ensure clinical accuracy, medical knowledge evolves rapidly; always verify drug dosages, indications, contraindications, and treatment protocols against official manufacturer prescribing information and national regulatory authorities. The views expressed do not necessarily reflect those of the publisher. Refer to the latest local and national guidelines for clinical practice.

References

1. Hwang S et al. Mechanism-based reporting patterns of infection-related adverse events with systemic psoriasis therapies in FAERS. J Dermatolog Treat. 2026 Dec undefined. doi: 10.1080/09546634.2026.2727193. PMID: 42806931.
2. Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic therapies for psoriasis. Int J Dermatol. 2019;58(6):649-658.
3. Armstrong AW, Puig L, Joshi A, et al. Comparison of Biologics and Oral Agents for Plaque Psoriasis: A Systematic Review and Network Meta-analysis. JAMA Dermatol. 2020;156(3):258-269.