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An investigational, topical cream that inhibits phosphodiesterase type 4 (PDE-4) was effective at clearing plaque psoriasis in a double-blind, phase IIb trial.

Meeting the trial's primary endpoint, 28% of patients treated with a 0.3% concentration of roflumilast and 23% of patients on a lower dose (0.15%) had clear or almost clear skin after 6 weeks, as compared to 8% of those given a placebo cream (P<0.001 and P=0.004 vs placebo, respectively), reported Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

Among the more than 300 patients in the study, 38% of those on roflumilast 0.3% cream achieved an investigator's global assessment (IGA) score indicating clear or almost clear skin at 8 and 12 weeks, the group reported in .

At these timepoints, respectfully, 31% and 32% of those on roflumilast 0.15% saw clear or almost clear skin, versus 12% and 16% for the placebo group.

Secondary endpoints were also met during the 12-week trial, with 31% of those on the higher dose of roflumilast achieving clear or almost clear skin along with a 2-grade improvement in the IGA score for the intertriginous area versus 14% of those on the placebo cream. In the lower-dose arm, 27% hit this target.

Among the 46 patients with mild psoriasis at baseline, 73% on the roflumilast 0.3% arm and 44% on the 0.15% arm reached this outcome by week 6, versus 29% of those on placebo.

"Plaque psoriasis imposes a significant burden on patients, and is often associated with poor quality of life," Lebwohl explained in a statement. "Effectively treating psoriasis with topical therapies, which the vast majority of patients receive, is especially challenging due to side effects, tolerability, or efficacy of existing topical treatments."

"Roflumilast cream could really be a game changer," he added.

Applied once daily, the anti-inflammatory topical cream contains the PDE-4 inhibitor roflumilast in a high-water-content cream base vehicle with the cosmetic solvent ethoxydiglycol. In tablet form, roflumilast (Daliresp) gained FDA approved in 2011 as a maintenance therapy for severe chronic obstructive pulmonary disease (COPD) exacerbations.

Another PDE-4 inhibitor, apremilast (Otezla), is and psoriatic arthritis, although is only available in oral form. Additionally, another PDE-4 inhibitor crisaborole (Eucrisa) is currently approved in an ointment formulation, but only for the treatment of atopic dermatitis.

For the current study, 331 adults with mild, moderate, or severe chronic plaque psoriasis -- affecting between 2% to 20% of the body-surface area (not including the scalp, palms, and soles) -- were randomized at 30 sites to one of three groups: roflumilast 0.3% (n=109), roflumilast 0.15% (n=113), or placebo cream (n=109). At baseline, all patients had at least a 2 out of 5 on the IGA scale for grading plaque thickening, scaling, and erythema. Those who scored for "mild" psoriasis were limited to only 20% of the cohort.

For safety, about 39% of patients on the higher-dose roflumilast cream experienced some form of adverse event, compared to 27% of those on the lower dose and 30% of those on placebo, although nearly all were categorized as mild or moderate. The most common events reported were upper respiratory tract infections, nasopharyngitis, and sinusitis.

Limitations to the trial included the short duration of only 6 weeks to assess the primary outcome, and the small proportion of patients with intertriginous psoriasis (roughly 15%).

The phase III clinical program of roflumilast is currently underway at Mount Sinai.

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