In this episode of Topical Conversations, Brad P. Glick, DO, MPH, and Aaron Farberg, MD, explore the advancements in treating generalized pustular psoriasis (GPP) with the introduction of subcutaneous spesolimab. They discuss the chronic nature of GPP, the trial data that led to the drug’s approval, and its significant impact on the treatment landscape and patient experience. 

A targeted agent for a challenging condition 

The conversation begins with an overview of spesolimab IV, highlighting its significance as the first FDA-approved systemic therapeutic agent for acute GPP flares. They discuss the challenges in managing this chronic, heterogeneous condition, which previously lacked specific therapeutic options, noting that spesolimab now provides a targeted treatment for the quiescent yet active phases of the disease. 

Addressing the educational gap and increased GPP awareness

Dr Farberg notes that he anticipates an increase in GPP diagnosis and treatment as awareness and education improve. He stresses the importance of having an effective, approved medication for GPP, noting the substantial impact compared to older, less targeted treatments. He also discusses the recent approval of subcutaneous spesolimab, which offers a new dosing option for sustained disease management between flares. 

Clinical insights on GPP management 

Dr Glick shares his clinical experiences managing GPP, particularly in acute settings such as hospitals and emergency rooms. He underscores the IL-36 pathway’s pivotal role in GPP pathogenesis and how spesolimab effectively targets this pathway. He highlights the transition from IV dosing in acute flares to subcutaneous dosing for ongoing disease control, enhancing long-term patient outcomes. 

Effisayil-2 data: chronic GPP treatment insights 

The conversation then addresses the Effisayil-2 trial data, a randomised, placebo-controlled, dose-finding phase 2b trial that assessed the efficacy and safety of spesolimab for GPP flare prevention. The study identified a higher dose every 4 weeks as most effective in preventing flares and maintaining disease control. This dosing regimen, which kept about 90% of subjects clear at 48 weeks, offers a promising long-term management strategy for this often unpredictable disease. 

Comparing IV and subcutaneous dosing 

Addressing a common clinical question, Drs Glick and Farberg discuss the differing roles of IV and subcutaneous spesolimab and whether subcutaneous dosing can be used in place of intravenous. The subcutaneous dose is 150 mg, while the IV dose is 900 mg; achieving the same bioavailability with subcutaneous dosing would require a high number of injections, highlighting the distinct roles of each. Dr Farberg recommends the IV version for acute flares due to its higher dosage and rapid effect. Dr Glick concurs, noting that patients with acute GPP require aggressive treatment, whereas subcutaneous dosing is ideal for maintaining stability between flares. 

The necessity of ongoing GPP management and flare prevention 

Dr Farberg emphasizes the importance of treating the chronic aspects of GPP to prevent flares, which significantly impact patients’ quality of life. The Effisayil-2 trial supports proactive management to mitigate these severe episodes and improve long-term outcomes. 

Safety and efficacy of subcutaneous spesolimab 

The doctors review safety and efficacy data from the Effisayil-1 and Effisayil-2 trials. While some patients experienced fatigue, infections, flu-like symptoms, and injection site reactions with the IV drug, the subcutaneous dosing showed fewer side effects, with some urinary tract infections being the most notable. 

Quality of life improvements 

The stable dosing regimen of subcutaneous spesolimab greatly enhances the quality of life for patients, their families, and caregivers. It simplifies the treatment process, making disease management more feasible and maintaining almost clear or clear conditions. This underscores the importance of having both IV and subcutaneous options, providing flexibility and comprehensive care for patients with GPP. 

Drs Glick and Farberg conclude that the availability of both IV and subcutaneous spesolimab marks a significant advancement in GPP management. These therapies not only improve patient outcomes but also enhance the overall treatment experience, offering improved quality of life for those affected by this challenging condition.