PROSE study finds treatment of disease not optimal

Patients with moderate-to-severe psoriasis who have not been previously treated with systemic therapies reported significant symptoms and considerable impairment in quality of life in the European, multicenter, open-label PROSE trial.

The trial evaluated treatment with the biologic secukinumab (Cosentyx, Novartis Pharma AG), in patients with psoriasis who had and had not received prior conventional or biologic systemic therapies, with quality of life (QoL) as a primary endpoint and family member QoL as a secondary endpoint.

Secukinumab was the first fully human IL-17A antagonist approved to treat moderate to severe plaque psoriasis, as well as psoriatic arthritis (PsA).

Two double-blind, year-long phase III trials sponsored by Novartis (ERASURE and FIXTURE) validated interleukin-17A as an important therapeutic target for the treatment of moderate-to-severe plaque psoriasis.

The biologic was approved by the FDA in 2016, and since then two other IL-17A antagonists – ixekizumab (Taltz, Eli Lilly & Co.) and brodalumab (Siliq, Ortho Dermatologics) have entered the market in the U.S.

In a recently published review examining IL-17A inhibitors in the treatment of psoriasis, researcher Esther von Stebut of the University of Cologne, Cologne, Germany, and colleagues concluded that the biologics may reduce risk associated with co-morbid cardiovascular disease and diabetes.

“Psoriasis skin manifestations, cardiovascular as well as metabolic disease in psoriasis appear to share pathogenic mechanisms evolving around IL-17 and its pro-inflammatory role,” they wrote. “First evidence suggests that anti-IL-17A therapy not only improves skin manifestations of psoriasis, but also cardiovascular inflammation as well as (potentially) metabolic factors.”

In the newly published study, patients who had not previously received systemic treatments had shorter time from diagnosis compared with patients who had received systemic treatments, but their disease was found to be associated with significant individual and family impact on quality of life.

“These (previously therapy naive) patients (were) in need of adequate treatment even though time since diagnosis was shorter,” wrote researcher Matthias Augustin, of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and colleagues in the Journal of the European Academy of Dermatology and Venereology.

“We also show for the first time that families of psoriasis patients are impacted in a similar manner as the patients. QoL of the caregivers deserves immediate attention and should be integrated into patient management.”

The study was conducted in 217 hospital-based and office-based investigational sites in 17 European countries and it included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis (total PASI score of ≥10, IGA mod 2011 ≥3 and a body surface area (BSA) ≥10% at baseline) diagnosed ≥3 months prior to screening.

Prior to entering the study, patients were either naive to systemic treatment (N= 663) or had previously been exposed to ≥1 systemic therapy, either conventional (N=673) or biologic (N=324). Patients previously treated with anti-IL-17A therapies (secukinumab, ixekizumab, or brodalumab) were excluded from the trial.

The three patient groups had similar demographic characteristics, but treatment-naive patients were more recently diagnosed (15.5±12.1 years compared with 19.1±12.5 years [conventional treatment] and 23.0±12.5 years [biologic treatment]).

Treatment naive patients also had lower rates of psoriatic arthritis (6.6% versus 17.4% and 27.8%, respectively).

Metabolic syndrome (37.6-43.5%), obesity (16.9-19.1%), hyperlipidemia (15.3‒21.9%) and diabetes mellitus (6.8‒14.2%) were reported at numerically higher rate in the biologic group.

The mean PASI (19.7±7.9), affected Body Surface Area (28.2±15.3%) as well as the Investigator Global Assessment score (patients with score 4: 33.7%) indicated severe disease at baseline and were comparable for the three groups, the researchers wrote.

Quality of life impairment was shown in both patient and family Dermatology Life Quality Index (DLQI) scores: patients 14.1±7.1; naive=13.5±6.8; conventional systemic=14.3±7.0; biologic=14.8±7.7) and family-DLQI (11.5±7.0: naive=11.3±7.1; conventional systemic=11.4±6.7; biologic=12.1±7.7).

A significant number of patients with psoriatic arthritis had not received previous systemic therapy before their enrollment in the PROSE study, which the researchers characterized as “concerning.”

“This re-emphasizes the fact that diagnosis and treatment of psoriatic arthritis is still not optimal and warrants urgent attention,” Augustin and colleagues wrote, adding that initiating certain biologic therapies early in the course of disease can prevent psoriatic-arthritis associated progression and joint destruction.

  1. Patients with moderate-to-severe psoriasis who have not been previously treated with systemic therapies reported significant symptoms and considerable impairment in quality of life.

  2. Quality of life impairment was also reported among family members of psoriasis patients in the study.

Salynn Boyles, Contributing Writer, BreakingMED™

This study was funded by Novartis Pharma AG. Researcher Matthias Augustin has served as a consultant and paid speaker for Norvartis and other pharmaceutical companies. Researcher Esteban Dauden has received advisory board, consultant and other frees from Novartis and other pharmaceutical companies. Several researchers were employees of Novartis during the conduct of this research.

Cat ID: 10

Topic ID: 75,10,10,105,192,158,68,919,925