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MIAMI BEACH -- An investigational phosphodiesterase-4 (PDE4) inhibitor may improve psoriasis, particularly for patients who haven't previously been treated, researchers reported here.

In a phase III randomized, controlled trial, significantly more patients on apremilast achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores over 16 weeks than those on placebo (33.1% versus 5.3%, P≤0.0001), reported Kristian Reich, MD, of Dermatologikum Hamburg in Germany, and colleagues.

About 36% of patients who had never received prior treatment with a biologic and 39% of those who'd never received any previous systemic therapy achieved that endpoint, they said at a late-breaking session at the American Academy of Dermatology meeting.

"It appears we could have here a new small molecule that we would possibly use ... to treat psoriasis earlier and to maybe be able to treat more moderate cases, which I think is needed ... in order to prevent metabolic comorbidities," Reich said.

Reich and colleagues conducted the ESTEEM-1 study, which enrolled 844 patients, mean age 46, with psoriasis to 16 weeks of treatment: 562 received 30 mg of apremilast twice a day, while 282 had placebo.

The primary outcome was PASI-75, or 75% reduction in PASI scores, as well as PASI-50 and static physician global assessment (sPGA) 0-1.

Reich described the baseline population as a "really comorbid one," with high mean body mass index (BMI) indicating obesity, high severity scores for psoriasis, long-standing disease, and relatively high use of previous therapies including tumor necrosis factor (TNF) inhibitor.

A total of 503 patients in the drug arm and 249 in the placebo group completed the trial.

Overall, they found "significant, moderate efficacy" with the drug at 16 weeks compared with placebo (P≤0.0001 for all):

• PASI-75: 33.1% versus 5.3%
• PASI-50: 58.7% versus 17%
• sPGA 0-1: 21.7% versus 3.9%

Reich noted that efficacy was especially good in the subgroup of patients who hadn't been previously treated with conventional or biologic therapy (38.7% and 35.8% achieving PASI-75, respectively).

However, even patients who had previously failed TNF treatment still showed a positive response, he noted, with 26.5% and 26.9% achieving PASI-75 with prior biologic and prior TNF therapy, respectively.

Overall, the mean percentage change in PASI score was about a 50% reduction for drug-treated patients compared with an approximately 20% reduction for the placebo group.

Reich added that patients on apremilast also had significantly better outcomes for secondary endpoints including quality of life, pruritus, scalp manifestations, and nail disease.

There was a similar proportion of adverse events in both groups, although the proportion of patients with at least one adverse event was higher with the drug (69.3% versus 55.7%).

There was more diarrhea and nausea with the drug than placebo which may explain a slightly higher withdrawal rate in the apremilast group. Reich noted that in most cases the intestinal effect last for about 2 weeks and then resolved.

"Obviously, there is some adaptation going on and I would say the gastrointestinal intolerance is mild to moderate in the majority of cases. Patients rarely need to withdraw and it seems to be transient in the majority of patients," Reich said.

An audience member commented that the high tolerability of the drug may suggest that higher doses should be tried for better efficacy, to which Reich replied that higher doses will likely be tested in future trials.

Another commenter noted that the benefits in terms of scalp and nail disease are impressive, and not currently seen with other small molecule drugs used to treat psoriasis, such as cyclosporine and methotrexate. "I think it's an added bonus along with the safety," the commenter said.

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