Team: The Oral Biologic Frontier
Authors: The Chicago Collaborative
- Maja Ivanovic, MD, first-year rheumatology fellow, University of Chicago
- Daming Shao, MD, first-year rheumatology fellow, University of Chicago
- Michael Macklin, MD, Assistant Professor of Medicine, University of Chicago
- Anu Pandit, MD, first-year rheumatology fellow, Northwestern University
- Laura Arneson, MD, Assistant Professor of Medicine, Northwestern University
- Aliya Ahsan, MD, first-year rheumatology fellow, Loyola University
- Mohit Gupta, MD, second-year rheumatology fellow, Loyola University
- Melissa Briones, MD, Associate Professor, Rheumatology, Loyola University
Team Overview:
Psoriasis is a multisystem, immune-mediated inflammatory disorder at the intersection of dermatology and rheumatology. Extensive skin involvement or concurrent arthritis may require an aggressive approach, beyond topical agents, phototherapy, or conventional synthetic DMARDs. The veteran oral options in this arena, apremilast and JAK/TYK2 inhibitors, have limitations in their efficacy and safety.
This phase 2 dose-finding randomized clinical trial introduces a promising prospect: the novel oral treatment JNJ-77242113, which exerts strong defense by inhibiting IL-23 and downstream cytokine production involved in plaque psoriasis. In this study, 255 patients with moderate-to-severe plaque psoriasis were randomized to receive the rookie therapeutic with doses of 25 mg daily, 25 mg twice daily, 50 mg daily, 100 mg daily, 100 mg twice daily, or placebo for 16 weeks. The primary endpoint was 75% reduction from baseline in the Psoriasis Area and Severity Index score (PASI 75). At 16 weeks, the young phenom, JNJ-77242113, outmaneuvered placebo, demonstrating a significant dose-response relationship, with 79% of patients reaching PASI 75 in the highest-dose group.
The stats show that this novel oral IL-23 receptor antagonist is a rising star. By combining the ease of oral administration with significant therapeutic efficacy, it opens the door to an arena of safer and more convenient treatments for psoriasis and has strong potential for psoriatic arthritis as well. The success of this therapy is a harbinger of the rising players capable of oral inhibition of cytokine targets more broadly, heralding an era where patients will not have to compromise efficacy for ease of use – a slam dunk for us all!
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