WAILEA, HAWAII (FRONTLINE MEDICAL NEWS) – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.

“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.

Apremilast, a selective phosphodiesterase-4 inhibitor marketed as Otezla, is in fact approved for two indications: moderate to severe psoriasis and active psoriatic arthritis.

“You have a drug that’s modest with regard to clearing psoriasis and it’s modest in controlling psoriatic arthritis. So you have to ask yourself what’s the patient population for this drug. I would just say that in my hands – and this is off-label – I use it only in patients with mild to moderate psoriasis,” Dr. Leonardi said.

“We all have psoriasis patients who come in with 3% or 4% of their skin involved, they’re actually using the class I topical steroids that I prescribe for them, yet they’re still not clear or almost clear and they want more. At that point, that’s when I might take them down this pathway and put them on apremilast along with a topical steroid. And I think that’s the appropriate place for this drug. I don’t use it in patients with 10% or more body surface area involvement,” he said.

He added that he would like to be able to prescribe apremilast in conjunction with a biologic agent in patients with more severe psoriasis to obtain synergistic efficacy, but payers balk at that because, at close to $3,000 per month, apremilast costs far more than methotrexate and other generic conventional disease-modifying antirheumatic drugs.

“The insurance industry is all over this drug. They require preauthorization, and they tell me, ‘No way, have a nice day,’ ” according to the dermatologist.

Dr. Leonardi described a couple of other practical caveats regarding apremilast. In patients with an estimated glomerular filtration rate below 30 mL/min per 1.73 m2, a dose reduction to 30 mg once daily in the morning is necessary. And apremilast is not recommended for use in patients who are on a strong inducer of the CYP 450 enzyme, such as rifampin or phenytoin.

An intriguing side effect of apremilast is that it causes weight loss: A 5%-10% weight loss was seen in the major psoriasis clinical trials. But it’s been established that there is no correlation at all between the weight loss and clinical efficacy for skin clearance.

What efficacy can be anticipated?

In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis ( J Am Acad Dermatol. 2015 Jul;73[1]:37-49 ), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.

Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo ( Ann Rheum Dis. 2014 Jun;73[6]:1020-6 ). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.

On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.

Symposium codirector Linda Stein Gold, MD , director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.

Finding potential in off-label use

“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD , director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.

Dr. Leonardi remained unpersuaded.

“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”

Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.

SDEF and this news organization are owned by the same parent company.


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