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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 effic...

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Autores principales: Gyldenløve, Mette, Meteran, Howraman, Sørensen, Jennifer A., Fage, Simon, Yao, Yiqiu, Lindhardsen, Jesper, Nissen, Christoffer V., Todberg, Tanja, Thomsen, Simon F., Skov, Lone, Zachariae, Claus, Iversen, Lars, Nielsen, Mia-Louise, Egeberg, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350848/
https://www.ncbi.nlm.nih.gov/pubmed/37465323
http://dx.doi.org/10.1016/j.lanepe.2023.100639
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author Gyldenløve, Mette
Meteran, Howraman
Sørensen, Jennifer A.
Fage, Simon
Yao, Yiqiu
Lindhardsen, Jesper
Nissen, Christoffer V.
Todberg, Tanja
Thomsen, Simon F.
Skov, Lone
Zachariae, Claus
Iversen, Lars
Nielsen, Mia-Louise
Egeberg, Alexander
author_facet Gyldenløve, Mette
Meteran, Howraman
Sørensen, Jennifer A.
Fage, Simon
Yao, Yiqiu
Lindhardsen, Jesper
Nissen, Christoffer V.
Todberg, Tanja
Thomsen, Simon F.
Skov, Lone
Zachariae, Claus
Iversen, Lars
Nielsen, Mia-Louise
Egeberg, Alexander
author_sort Gyldenløve, Mette
collection PubMed
description 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 10.13039/501100002918Gentofte Hospital, 10.13039/501100001734University 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.
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spelling pubmed-103508482023-07-18 Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO) Gyldenløve, Mette Meteran, Howraman Sørensen, Jennifer A. Fage, Simon Yao, Yiqiu Lindhardsen, Jesper Nissen, Christoffer V. Todberg, Tanja Thomsen, Simon F. Skov, Lone Zachariae, Claus Iversen, Lars Nielsen, Mia-Louise Egeberg, Alexander Lancet Reg Health Eur Articles 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 10.13039/501100002918Gentofte Hospital, 10.13039/501100001734University 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. Elsevier 2023-04-21 /pmc/articles/PMC10350848/ /pubmed/37465323 http://dx.doi.org/10.1016/j.lanepe.2023.100639 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Gyldenløve, Mette
Meteran, Howraman
Sørensen, Jennifer A.
Fage, Simon
Yao, Yiqiu
Lindhardsen, Jesper
Nissen, Christoffer V.
Todberg, Tanja
Thomsen, Simon F.
Skov, Lone
Zachariae, Claus
Iversen, Lars
Nielsen, Mia-Louise
Egeberg, Alexander
Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title_full Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title_fullStr Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title_full_unstemmed Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title_short Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
title_sort efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (psorro)
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350848/
https://www.ncbi.nlm.nih.gov/pubmed/37465323
http://dx.doi.org/10.1016/j.lanepe.2023.100639
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