Pyoderma gangrenosum (PG) is a rare, ulcerative neutrophilic dermatosis characterised by dysregulation of the Th1/Th17 axis and overexpression of interleukin-17 (IL-17). We describe a 52-year-old woman with Hurley stage 3 hidradenitis suppurativa (HS) who developed several PG ulcers on the lower extremities that were refractory to interleukin-12/23 inhibition (ustekinumab) and IL-17A inhibition (secukinumab). Transition to bimekizumab—a monoclonal antibody that selectively inhibits both IL-17A and IL-17F—resulted in complete healing within 2 months and marked improvement in HS, pain, and quality-of-life scores. This case highlights not only the potential efficacy of dual IL-17A/F inhibition in PG associated with HS but also the impact on quality of life and pain. A 52-year-old woman with a history of breast cancer and Hurley stage 3 HS presented with new bilateral lower-extremity ulcers of 1.5 months' duration shortly after a single 90 mg subcutaneous dose of ustekinumab. She had previously achieved HS control with infliximab, which was discontinued after her breast cancer diagnosis. The ulcers began as erythematous papules and pustules that ulcerated after scratching. Examination revealed a right-leg ulcer (2 cm × 1 cm) extending to subcutaneous tissue with a violaceous border, and similar smaller ulcers and a pustule with erythematous border on the left leg. Her PARACELSUS diagnostic score was 11, consistent with PG. Ustekinumab (90 mg) was continued for HS and PG, but after 3 months the ulcers showed no improvement. Secukinumab (300 mg weekly for 4 weeks, then every 4 weeks) induced partial response: all lesions healed over 8 months except for a persistent right-shin ulcer (0.3 cm × 0.6 cm) present for 9 months (Figure 1). Her HS did not respond to secukinumab. Bimekizumab (320 mg) was then initiated. Baseline pain on the Numeric Rating Scale (NRS) was 7/10 (Figure 2a). Skindex-Mini scores indicated severe quality-of-life impairment (83–100 across symptoms, emotions, and functioning; Figure 2b) 1; her Patient Global Assessment (PtGA) was 3 (moderate disease activity). After two 320 mg doses spaced 2 months apart, the PG ulcers completely healed (Figure 1). NRS pain score was 1, Skindex-Mini scores decreased to 0, and PtGA decreased to 1. HS activity also decreased, with reduced drainage and fewer draining sinus tracts. Bimekizumab was well tolerated. PG is a debilitating ulcerative dermatosis lacking Food and Drug Administration approved therapies; management relies on long-term immunosuppression with attendant risks. Biologic agents such as tumour necrosis factor-α (TNF-α) inhibitors can be effective but may be contraindicated in patients with recent malignancy, demyelinating disease, or heart failure. The initial trigger for PG is still unknown, though the inciting event may activate the complement system and induce neutrophil extracellular trap (NET) formation, creating a positive feedback loop in the T-helper (Th) response 2. Moreover, myeloid cells are the predominant cell type in PG and drive the changes in gene expression in perilesional skin of PG 3. Thus, biologics that target the Th pathway and affect the function of myeloid cells, such as IL-17 inhibitors, might be beneficial in the treatment of PG. Bimekizumab selectively neutralises IL-17A and IL-17F, providing a broader IL-17 pathway suppression than IL-17A–only inhibitors, such as secukinumab. IL-17 promotes matrix metalloproteinase production, neutrophil recruitment, and pro-inflammatory cytokine expression—including IL-1β, IL-6, and TNF-α—all of which are overexpressed in PG and implicated in NETosis 2, 4. Bimekizumab also down-regulates downstream inflammatory pathways STAT3 and NF-κB, which are up-regulated in PG lesional tissue 2, 4. Dual IL-17A/F blockade has demonstrated efficacy in other immune-mediated diseases, including HS and psoriasis. In a head-to-head trial in plaque psoriasis, bimekizumab produced greater skin clearance than secukinumab, supporting the concept that dual inhibition yields greater clinical benefit than IL-17A blockade alone 5. Notably, our patient failed secukinumab yet responded to bimekizumab, reinforcing this rationale. As with secukinumab, bimekizumab is not recommended in patients with inflammatory bowel disease (IBD). Bimekizumab induced complete healing of refractory PG in a patient who had failed both ustekinumab and secukinumab, with concomitant improvements in pain, quality of life, and HS activity. As a single case report, this study has inherent limitations in generalizability; however, it highlights the need for and encourages further investigation in this area. Although topical tacrolimus was administered concurrently with bimekizumab, the patient had previously received this topical therapy for 10 months alongside other biologics without resolution. Overall, this experience underscores the therapeutic potential of dual IL-17A/F inhibition in PG—especially in patients with HS and without IBD—and supports further investigation of bimekizumab in clinical studies for recalcitrant patients of PG or PG associated with genetic syndromes (e.g., pyoderma gangrenosum, acne, and hidradenitis suppurativa or PASH). The authors have nothing to report. A.G.O.-L. is the former President of the Pacific Dermatology Association and serves as an associate editor for Dermatology (Karger) and editorial board member of the American Journal of Clinical Dermatology. Additionally, he is a consultant for Genentec, Guidepoint, InflaRx, Corvus pharmaceuticals, Castle Biosciences, Clarivate, TFS HealthScience, Otsuka, and Leo Pharma. He is an advisor to Bristol-Meyers Squibb, Boehringer Ingelheim, Janssen, and Sanofi. Dr. Ortega has received research grants from Lilly, Janssen, Incyte, and Pfizer. He is supported by National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01 AR083110. The other authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Oberg et al. (Wed,) studied this question.