Home Medizin Experimentelles topisches Medikament ist vielversprechend bei AD und Psoriasis

Experimentelles topisches Medikament ist vielversprechend bei AD und Psoriasis

von NFI Redaktion

VON JAMA DERMATOLOGY

Results from a phase 2a study showed that an experimental topical phosphodiesterase 4 (PDE4) inhibitor demonstrated superior efficacy compared to the vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis.

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because „they increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,“ wrote lead study author Lawrence F. Eichenfield, MD, from the dermatology department at the University of California, San Diego, and colleagues. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has been shown to be effective for plaque psoriasis and is well-tolerated, but „has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,“ wrote the researchers.

For AD, crisaborole is the only approved topical PDE4 treatment and is associated with burning and stinging at the application site, they wrote.

An Experimental Alternative

In the new study, a topical PDE4 inhibitor called PF-07038124, developed by Pfizer, was tested. It is expected to be „an effective PDE4 inhibitor based on oxaborole“ that shows immunomodulatory activity in T-cell-based tests contributing to the inhibition of interleukin-4 and IL-13. Therefore, it could offer therapeutic benefit in the treatment of AD and plaque psoriasis, the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary endpoint was the percentage change in the Eczema Area and Severity Index (EASI) total score in AD patients and the Psoriasis Area and Severity Index (PASI) score in plaque psoriasis patients from baseline at week 6. Safety measures of interest included treatment-related adverse events.

The average age of the 104 patients was 43 years, 52.9% were women, 3.8% were Asians, 12.5% were Black, and 83.7% were White. Most had a moderate disease.

In week 6, the PF-07038124 group showed a statistically significantly greater improvement in the EASI total score compared to the vehicle group in patients with AD (–74.9% vs. –35.5% [least squares mean]). [LSM difference: −39.4%; 90% CI: −58.8% to −20.1%]; P < .001).

Similarly, the PF-07038124 group showed a significantly greater improvement in the PASI total score compared to the vehicle group in week 6 in patients with plaque psoriasis (LSM, –4.8; 90% CI, –6.2 to –3.4]vs.0.1; 90% CI, –1.5 to 1.7), for a difference of –4.9; 90% CI: –7.0 to –2.8; P < .001.

Treatment-related adverse events were reported in 16 individuals receiving PF-07038124 and in 26 individuals receiving a vehicle. Treatment-related adverse events were reported only in the vehicle groups for all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the study, including its small size and six-week treatment duration. „In contrast to crisaborole, the topical application of PF-07038124 was not associated with burning and stinging at the application site,“ they noted. „To confirm the continued efficacy and safety profile of PF-07038124, long-term data should be collected in larger studies.“

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. Additionally, he received grants from several other pharmaceutical companies, is a consultant for them, and/or serves on their advisory boards. Several other study authors reported similar disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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