Generalized Pustular Psoriasis Treated With Risankizumab
PRACTICE POINTS
- Generalized pustular psoriasis (GPP) is a potentially life-threatening condition that can be precipitated by systemic steroids.
- Although more than 20 systemic medications have been tried with varying success, there has not been a single US Food and Drug Administration–approved medication for GPP until recently with the approval of spesolimab, an IL-36 receptor inhibitor.
- Risankizumab, a high-affinity humanized monoclonal antibody that targets the p19 subunit of the IL-23 cytokine, also has shown promise in a recent phase 3, open-label study for GPP.
Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.5 In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),5 an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.
Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.11 However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.
A number of questions still need to be answered regarding treating GPP with risankizumab:
• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?12
• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?
• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).
• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.13
• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?5
Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.
Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications3 and phase 3, randomized, placebo-controlled studies.5 We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.
