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Oral apremilast (Otezla) has been approved by the FDA for the treatment of moderate-to-severe plaque psoriasis, manufacturer Celgene announced.

Apremilast is a selective inhibitor of phosphodiesterase 4 which increases intracellular levels of cyclic adenosine monophosphate, which in turn modulates inflammatory mediators such as tumor necrosis factor and interleukin 23. This is the first of a new class of oral medications, explained Mark Lebwohl, MD, chairman of dermatology at the Mount Sinai Health System in New York, who participated in the drug's clinical trials.

"This is the first oral treatment for psoriasis that's been approved in decades. Most of the newer treatments for psoriasis have been injectable, so apremilast might be particularly helpful for patients who are needle-phobic," Lebwohl told 名媛直播.

Unlike some other psoriasis treatments, routine blood monitoring is not required, he noted.

Efficacy was evaluated in two pivotal trials, ESTEEM 1 and 2, which included 1,250 adults who had plaque psoriasis of at least a year's duration and who also were considered suitable candidates for systemic treatment and/or phototherapy.

The design of the two multicenter trials involved an initial 5-day titration period and then 16 weeks of treatment with 30 mg twice daily or placebo. Between weeks 16 and 32, patients previously receiving placebo were switched to the active treatment, and weeks 32 to 52 were a randomized withdrawal phase for responders.

ESTEEM 1 included 844 patients whose mean Psoriasis Area and Severity Index (PASI) score was 19 at baseline.

After 16 weeks of treatment, 33.1% receiving 30 mg of apremilast twice daily had improved by 75% on PASI, compared with 5.3% of those on placebo, while 50% improvements were seen in 58.7% versus 17% (P<0.0001), the company reported in a poster session at the 2014 annual meeting of the American Academy of Dermatology.

Improvements in PASI of 81% to 88% were seen between weeks 32 and 52 among the 77 patients who received the active treatment for the entire year and who had achieved a PASI75 by week 32, the company reported in a press release.

In the week 32 to 52 withdrawal phase, among those who initially had PASI75 responses and who were re-randomized to placebo, 11.7% still had PASI75 responses by week 52, and the median time to loss of response had been 5.1 weeks.

After restarting apremilast treatment, 70.3% were able to again achieve a PASI75 response.

That trial also found benefits for difficult-to-treat psoriasis. Among 46 patients who had nail psoriasis, a 60.2% decrease on the Nail Psoriasis Severity Index (NAPSI) was seen at 1 year, and among the 49 who had at least moderate involvement of the scalp, a "meaningful improvement" occurred, with 72.9% being "clear or almost clear" after a year of treatment.

In ESTEEM 2, PASI75 responses were observed among 28.8% of patients receiving 30 mg twice daily by week 16 compared with 5.8% of those given placebo (P<0.0001).

Benefits also were seen for difficult-to-treat areas in ESTEEM 2, according to the company. For the scalp, 40.9% receiving the active treatment were clear or almost clear at week 16 compared with 17.2% of those on placebo (P<0.0001), while 50% improvements on NAPSI were reported by 44.6% versus 18.7%, P<0.0001).

A safety analysis of ESTEEM 1 found no unexpected adverse events through 52 weeks, and the most common adverse events were diarrhea (18.7%), upper respiratory tract infection (17.8%), nausea (15.3%), nasopharyngitis (13.4%), tension headache (9.6%), and headache (6.5%).

Fewer than 2% of patients discontinued because of the gastrointestinal events. "The GI side effects by and large diminish after the first month," Lebwohl said.

Rates of serious adverse events were similar to those seen with placebo.

Patients taking the drug are advised to tell their physician if they experience symptoms of depression or other mood changes, the company noted. In clinical studies, 1% of patients reported these events, 0.3% stopped treatment because of depression, and 0.2% reported suicidal ideation.

Some patients also lost 5% to 10% of their body weight.

There were no cases of lymphoma, tuberculosis, or serious opportunistic infections through week 16, and no increase in cardiovascular risk was seen. Serious adverse events were reported in fewer than 3% of patients in the active treatment and placebo groups.

In an earlier , patients receiving 30 mg twice daily had an odds ratio of achieving PASI75 of 11.5 (95% CI 4.24-31.2, P<0.0001) by week 16.

Apremilast was approved in March for the treatment of psoriatic arthritis. It had been evaluated in a yearlong trial known as PALACE 1, which included more than 500 patients with active disease. In that study, 63% of patients receiving 20 mg twice daily had a 20% reduction in symptoms, as did 54.6% of those given 30 mg twice daily.

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