Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background

Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied.

Methods

A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 μg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12.

Findings

In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events.

Interpretation

Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments.

Funding

Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

Informations de copyright

© 2023 Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

The Danish market authorization holder of roflumilast was informed prior to study initiation but did not provide any financial or in-kind support for the trial. None of the investigators hold any financial interest in the study drug. Mette Gyldenløve: Research funding from the Kgl. Hofbuntmager Aage Bang Foundation, the Danish Psoriasis Foundation, Fonden af familien Kjærsgaard, Sunds, the Simon Spies Foundation, and the CC. Klestrup og hustru Henriette Klestrups Mindelegat. Four-year postdoctoral stipend (2022–26) from Herlev and Gentofte Hospital, University of Copenhagen. Howraman Meteran: Research funding from Per Henriksens Fond, Danish Lung Association, and ALK-Abelló. Honoraria as consultant and/or speaker for ALK-Abelló, GSK, Novartis, AstraZeneca, Sanofi-Aventis Denmark, Airsonett AB, and Teva. Jennifer A. Sørensen: None. Simon Fage: Investigator for AbbVie, Galderma, UCB, Eli Lilly, Novartis, and LEO Pharma. Yiqiu Yao: None. Jesper Lindhardsen: None. Christoffer Nissen: None. Tanja Todberg: Investigator for Novartis, AbbVie, Dr. Wolff, Galderma, and Almirall. Simon F. Thomsen: Research funding from Janssen Pharmaceuticals, LEO Pharma, Novartis, Sanofi and UCB. Honoraria as consultant and/or speaker for Novartis, CSL, Sanofi, Union Therapeutics, LEO Pharma, Pfizer, Sanofi, and AstraZeneca. Lone Skov: Research funding from Almirall, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish Psoriasis Foundation, the LEO Foundation, and the Kgl. Hofbundtmager Aage Bang Foundation. Honoraria as consultant and/or speaker for AbbVie, Eli Lilly, Novartis, Pfizer, LEO Pharma, Janssen Cilag, UCB, Almirall, Bristol-Myers Squibb, Boehringer Ingelheim, Novo, and Sanofi. Investigator for AbbVie, Pfizer, Sanofi, Janssen Cilag, Boehringer Ingelheim, Eli Lilly, Novartis, Galderma, and LEO Pharma. Claus Zachariae: Paid speaker for Eli Lilly, Novartis, CSL, and LEO Pharma. Consultant and/or advisory board member for AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Takeda, Amgen, and CSL. Lars Iversen: Consultant and/or speaker honoraria from AbbVie, BMS, LEO Pharma, Novartis, UCB, Janssen Pharmaceuticals, Boehringer Ingelheim, and Regranion. Part-time employment at MC2 Therapeutics. Mia-Louise Nielsen: None. Alexander Egeberg: Research funding from the Danish Psoriasis Foundation, the Kgl. Hofbuntmager Aage Bang Foundation, the Simon Spies Foundation, Pfizer, Eli Lilly, Novartis, AbbVie, and Janssen Pharmaceuticals. Consultant and/or speaker honoraria from AbbVie, Almirall, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Galápagos NV, Horizon Therapeutics, Janssen Pharmaceuticals, LEO Pharma, Mylan, Novartis, Pfizer, Samsung Bioepis Co., Ltd., UCB, and Union Therapeutics.