Clinical advances in biological therapy for generalized pustular psoriasis: a review

ABSTRACT

Introduction

In 2022, U.S. Food and Drug Administration (FDA) approved the first biologics, intravenous spesolimab, for acute flare of generalized pustular psoriasis (GPP). The drug works by blocking IL-36 signaling, the key pathway of GPP. Among the known mutations causing GPP, IL36RN mutations are most common, and the presence of IL36RN mutations had been found to affect the clinical manifestations and treatment response of GPP.

Areas covered

Literature search was conducted in PubMed, Embase and ClinicalTrials.gov for relevant studies discussing biologic treatment for GPP with special emphasis on larger studies, pediatric group, pregnant women, and the influence of IL36RN mutation on the effectiveness of biologics.

Expert opinion

The approval of spesolimab for GPP flare treatment marks a new era. However, whether spesolimab will be placed as the treatment of choice remains unknown, considering its higher cost, lack of direct comparison with existing biologics, and uncertain effects on co-existing plaque-type psoriasis. However, the demonstration of numerically better efficacy for patients carrying pathogenic IL36RN mutations suggests the role of pharmacogenetics in the choices of GPP treatment. Future randomized studies are warranted to investigate the effectiveness and safety of biologics for GPP in pediatric and pregnant groups.

KEYWORDS:

• Biologics
• children
• deficiency of interleukin-36-receptor antagonist (DITRA)
• deficiency of interleukin-1-receptor antagonist (DIRA)
• GPP (generalized pustular psoriasis)
• IL36RN mutation
• pustular psoriasis
• pregnancy

Article highlights

• Most biologics approved for the treatment of plaque-type psoriasis vulgaris, including infliximab, adalimumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, certolizumab pegol, and bimekizumab have also been approved for GPP in Japan based on open-label studies of small sample size.

• U.S. Food and Drug Administration (FDA) approved the first biologics, intravenous spesolimab, for GPP acute flare in 2022, and the efficacy of subcutaneous spesolimab for flare prevention has been shown in a recent randomized study.

• Spesolimab is a IL-36 receptor antagonist, and both patients with or without IL36RN mutations may respond to spesolimab. However, it is likely that spesolimab will be especially useful for patients carrying pathogenic IL36RN mutations.

• For pregnant women, certolizumab appeared to be a reasonable and safe choice due to minimal transplacental transfer.

• Currently, no biologics have been approved for the treatment of pediatric GPP, but secukinumab represents the most widely reported one. The randomized controlled trial, Effisayil 2, includes adolescents older than the age of 12, but the result is still pending for this age group and the number of pediatric patients remains limited.

Declaration of interest

CY Hsieh received honoraria for educational events from Boehringer Ingelheim. TF Tsai has conducted clinical trials or received honoraria for serving as a consultant for Abbvie, AnaptysBio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, Galderma, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme, Novartis International, Pfizer, PharmaEssentia, Sanofi, Sun Pharma, and UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

CY Hsieh drafted this manuscript. TF Tsai is responsible for the conceptualization and the final refinement.

Additional information

Funding

This paper was not funded.