LAUSR

Dear Editor Biologics are revolutionary therapies for psoriasis. Different classes of biologics may be required due to the inefficacy in clinical practice. To date, no studies have assessed the switch between two newer biologics, guselkumab and ixekizumab, which are interleukin (IL)-23 and IL-17 antibodies, respectively. We report a case of guselkumab-resistant psoriasis that was successfully treated with ixekizumab. A 35-year-old man has been diagnosed with psoriasis for 15 years. He has neither extracutaneous symptoms nor systemic diseases; however, he has felt overwhelmed with work and life. The disease was relapsing-remitting with multiple therapies that have not worked, including narrowband ultraviolet B phototherapy, acitretin, cyclosporine, etanercept, and ustekinumab. Owing to the inefficacy of conventional therapies and older biologics (etanercept and ustekinumab), guselkumab was administered 15 months ago when his psoriasis area and severity index (PASI) score was 27.1. Improvement of skin lesions was experienced initially, with the nadir of the PASI score at 10.6 after 12 weeks. However, loss of response to guselkumab was observed in the following days; his PASI score rose to 18.0 after 28 weeks. Guselkumab was withdrawn due to its inefficacy (Figure 1A-C). After 8 weeks, the patient began ixekizumab treatment (160 mg starting dose, followed by 80 mg every 2 weeks through week 12, then 80 mg every 4 weeks). This created a marked improvement in cutaneous lesions in 2 weeks and achieved 100% improvement from baseline (PASI-100 response) after 10 weeks. To date, he has continued with ixekizumab treatment and the PASI score of 0 was maintained for more than 7 months (Figure 1D-F). To the best of our knowledge, this is the first report of successful treatment of guselkumab-resistant psoriasis with ixekizumab. Guselkumab is a fully human immunoglobulin (Ig) G1 λ monoclonal antibody that blocks the IL-23-mediated signaling pathway. Guselkumab is superior to adalimumab and placebo treatment at week 16; a greater proportion of patients achieved PASI-75 response (91% vs 73% vs 6%). Continuous guselkumab treatment for psoriasis may conduces to 82% of patients reporting PASI-90 response at week 100. Ixekizumab is a humanized IgG4 monoclonal antibody that blocks IL-17A. Greater proportions of ixekizumab-treated patients achieved PASI-75 response (89%) when compared with placebotreated patients (4%) at week 12. Following 52 weeks' continuous therapy, a significantly higher proportion of ixekizumab-treated patients can reach PASI-90 response (77%) than ustekinumab-treated patients (59%). Studies have indicated that guselkumab and ixekizumab are promising therapies for >80% psoriasis patients. However, a few patients are unresponsive to these biologics. Despite widespread usage, there are limited data on switching biologics that target IL17/IL23 pathway. By targeting the IL23-specific p19 subunit, guselkumab acts upstream of the IL/17/IL23 pathway. It reduces not IL-17A but also IL-17F, IL-21, and IL-22. Additionally, guselkumab can neutralizes IL-39 which causes proinflammatory effects in psoriasis. Ixekizumab directly against IL-17A can antagonizes the IL-17/IL23 pathway downstream. It also blocks IL-17A derived from immune cells other than Th17, such as neutrophils and mast cells. These innate immune cells can produce IL-17A independently of IL-23. Accordingly, ixekizumab blocks IL-17A more fully and alleviates the dysregulated innate and adaptive immune systems in psoriasis. Guselkumab and ixekizumab act in different mechanism and have their own therapeutic advances. Studies have emphasized that prior biologic failure does not mean a loss of response to another biologic. Hence, patients who show a poor response to guselkumab might benefit from switching to ixekizumab and vice versa. Biologic switching policies in psoriasis should be individualized based on pharmacologic characteristics, therapeutic response, and patient's clinical needs. Our report can help physicians managing inefficacy in patients with biologic-treated psoriasis. Further studies are required to confirm the efficacy of biologic switch. We would like to thank the patient cited in this manuscript that has given a written informed consent to the publication of his case details and photographs.