Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults

ABSTRACT

Introduction

Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE.

Areas covered

Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and −2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and −2). Based on the DISCOVER-1 and −2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020.

Expert Opinion

Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

KEYWORDS:

• Guselkumab
• interleukin-23
• psoriasis
• psoriatic arthritis
• p19
• risankizumab
• tildrakizumab

Company review

During the peer review process, Janssen Pharmaceuticals Inc., the marketing-authorization holder of guselkumab, was offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Article highlights

• Guselkumab binds to the p19 subunit of IL-23 and is thus a specific and selective inhibitor of this cytokine.

• Guselkumab affects regulatory mechanisms of the immune system, which explains the convenient long interval of two months between applications.

• Guselkumab reached the primary efficacy end point (ACR20 response at week 24) in both of the pivotal DISCOVER-1 and −2 phase-3 psoriatic arthritis trials.

• ACR20 response patterns are consistent in psoriatic arthritis patients with and without previous TNF inhibitor use, including patients who previously demonstrated an inadequate response to TNF inhibitors.

• Based on the results of the clinical development program, guselkumab has become the first molecule of its class approved for the treatment of adults with active psoriatic arthritis.

Disclosure statement

W-H Boehncke received honoraria as a speaker/advisor from Abbvie, Almirall, Amgen, Celgene, Janssen, Leo, Lilly, Novartis and Pfizer, and received a research grant from Pfizer. MJ Nissen received honoraria as a speaker/advisor from Abbvie, Celgene, Lilly, Novartis, Pfizer and received research grants from Abbvie, is a member of the Novartis sponsored EuroSpA collaboration of European SpA registries. 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.

Additional information

Funding

This paper was not funded.