Connecting the Dots: A Potential Mechanism for Increased Rates of Nasopharyngitis in Secukinumab-Treated Patients
Author Type(s)
Resident/Fellow
Document Type
Abstract
Publication Date
2022
DOI
10.1016/j.jaad.2022.06.175
Journal Title
Journal of the American Academy of Dermatology
Department
Dermatology
Abstract
Background: Secukinumab is a human immunoglobulin G1-kappa monoclonal antibody that targets and inhibits cytokine interleukin (IL)-17A. Secukinumab successfully treats conditions in which IL-17A plays a role, including psoriasis, psoriatic arthritis, and ankylosing spondylitis. While there are no reports of dangerous adverse effects with secukinumab treatment, there is a notable increase in nasopharyngitis and upper respiratory infections (URI). Herein we investigate potential mechanisms to explain the increased rates of URI amongst patients treated with secukinumab. Methods: We conducted a literature review using PubMed and search terms “secukinumab,” “secukinumab adverse events,” “secukinumab phase 3,” “psoriasis transcriptome,” “nasopharyngitis,” and “DEFB4.” Approximately 120 articles were evaluated. Only articles in the English language were evaluated. Results: IL-17A exerts its inflammatory and proliferative effects via IkBζ. Secukinumab treatment downregulates IkBζ signature genes such as DEFB4. DEFB4 codes for β-defensin-2 (BD-2). BD-2 is an antimicrobial peptide that is expressed in human lung, trachea, and skin. BD-2 is effective against Gram-negative bacteria such as Haemophilus influenza, Moraxella catarrhalis, and fungi such as Candida albicans. BD-2 also disrupts viral replication of rhinovirus, adenovirus, and influenza. Downstream of IL-17A, BD-2 levels are increased in psoriatic skin lesions. As secukinumab decreases IL-17A, BD-2 is downregulated not only in psoriatic lesions, but also in the lungs and trachea, thereby leading to weakened defenses against common nasopharyngitis and URI pathogens. Conclusion: While nasopharyngitis is a largely benign adverse effect of secukinumab, this potential mechanism of action emphasizes caution when using secukinumab in patients with an increased risk for Gram-negative infections.
Recommended Citation
Guenin, S. H., Cline, A., & Schulz, A. (2022). Connecting the Dots: A Potential Mechanism for Increased Rates of Nasopharyngitis in Secukinumab-Treated Patients. Journal of the American Academy of Dermatology, 87 (3), AB35. https://doi.org/10.1016/j.jaad.2022.06.175
