Case Report: Interleukin-23 blockade achieves sustained remission in Niemann-Pick type C-associated Crohn's disease refractory to anti-tumor necrosis factor therapy.

Background: Niemann-Pick type C (NPC) is a lysosomal lipid trafficking disorder that is associated with defective autophagy and impaired bacterial clearance, potentially predisposing patients to Crohn's disease (CD)-like granulomatous enteritis. Tumor necrosis factor-alpha inhibitors are typically the first-line biologic treatment for CD. However, due to limited evidence-based data, the optimal treatment for NPC-associated CD remains unclear. Case presentation: A 20-year-old female patient with genetically confirmed NPC developed diarrhea and refractory perianal abscesses at the age of 17 years. Colonoscopy showed discontinuous longitudinal erosions, and histological examination revealed chronic inflammation with granulomas. Based on these finding, a diagnosis of CD complicating NPC was made. Adalimumab was not successful in maintaining remission despite corticosteroid therapy. Ustekinumab induced steroid-free remission. Nevertheless, its effect diminished before each dosing interval. Switching to risankizumab achieved stable remission, which was maintained for 3 years. During interleukin (IL)-23 blockade therapy, the patient developed an infection associated with an intrathecal baclofen pump. Conclusion: This case indicates that IL-12/23 and IL-23 inhibitors can be effective therapeutic options for NPC-associated CD. Furthermore, it supports the hypothesis that IL-23-driven inflammation plays a role in the development of this condition. These findings should be considered hypothesis-generating and validated in additional cases.