The P2X7-NLRP3 inflammasome inhibitor AZD9056 has no significant effect on hidradenitis suppurativa clinical disease activity but restores cytokine production in peripheral blood mononuclear cells: Results of a phase 2 trial
Journal of the American Academy of Dermatology, 2025
Kilgour J., Landy H., Kimball A., Resnik B., Anadkat M., Dhawan S., de Souza M., Sarin K.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Pathophysiology | Cell Culture Supernatant |  Olink Target 96 |
Abstract
A growing body of evidence has implicated the NLRP3 inflammasome in the inflammatory cascade associated with autoimmune and autoinflammatory diseases, including hidradenitis suppurativa (HS). The NLRP3 inflammasome is a multiprotein complex that, upon activation, triggers the release of multiple proinflammatory cytokines involved in the pathogenesis of HS.1 The P2X7 ATP-gated ion channel receptor is an upstream regulator of NLRP3 and plays a pivotal role in inflammasome activation and cytokine release. Immunohistochemical studies have shown upregulation of both complexes in HS lesions,2 highlighting their potential pathophysiologic role. AZD9056 is a P2X7 antagonist that was well-tolerated in prior phase 2 clinical trials conducted by AstraZeneca. We report here a phase II, multicenter, randomized-controlled, double-blind clinical trial of AZD9056 in HS.