Canadian investigators have determined that apremilast—an oral phosphodiesterase 4 inhibitor—can be safely and effectively combined with at least one form of photosystemic, and/or biologic therapy in the treatment of patients with chronic plaque psoriasis.
During a retrospective review, published online ahead of print in the Journal of Cutaneous Medicine and Surgery (July/August 2016; 20(4):313-316), researchers found that 81 patients with plaque psoriasis were treated with apremilast in combination with at least one other therapy. The other therapies included NB-UVB, methotrexate, acitretin, cyclosporine, etanercept, adalimumab, infliximab, or ustekinumab.
Of those 81 patients, 14 (17%) discontinued treatment before completion of the 12 weeks of apremilast therapy, however, 67 patients continued on the drug past 12 weeks. Eighty-one per cent achieved at least 75% improvement in the Psoriasis Area and Severity Index score (PASI- 75) at week 12 after apremilast was added to an existing therapy, the authors reported in the article.
Well-tolerated and effective “[Some patients] have been through a number of treatments. They have a difficult disease and they [were] on some other therapy—whether light therapy, an oral therapy, or a biologic—but they just needed a little bit more to be clear,” said study author Dr. Neil Shear, professor in the Division of Dermatology, Department of Medicine at the University of Toronto and head of dermatology at Sunnybrook Health Sciences Center. “We added [apremilast] because we wanted to see if it was tolerated and if it would help. It seemed to do all those things—it was tolerated, it was safe, and people tended to do much better.”
Reported side effects included nausea and/or diarrhea in 25% of patients. “For most of those people, [the soft stool] goes away, but for some it does not and we have to change the medication,” said Dr. Shear. “Patients tend to feel good on [apremilast] and some, [about 15 per cent, experienced] weight loss, which they did not seem to mind. [This was] not related to the diarrhea or anything, [the apremilast] just seems to have an effect on fat cells.”
Most patients who experienced diarrhea continued to take apremilast and their symptoms usually resolved after a week or two, he said. Using the apremilast starter pack reduces the incidence of diarrhea. The pack starts with 10 mg in the evening on day one, then 10 mg in the morning and in the evening on day two, then 10 mg in the morning and 20 mg in the evening on day three, then 20 mg in the morning and in the evening on day four. On day five, the patient takes 20 mg in the morning and 30 mg in the evening, and then on day six and thereafter 30 mg in the morning and in the evening.
Convenient method of delivery
Patients expressed the opinion that apremilast is a convenient therapy to add to an existing treatment, noted Dr. Shear, because it only requires taking one pill twice a day. He hypothesized that the rate of compliance is high.
“When people are clear [from psoriasis] they do not want to stop anything,” said Dr. Shear. “When they are clear they say, ‘I [would like to] keep taking this, anything wrong with that?’ I say, ‘no, it is OK, but we will just keep [monitoring you]'.” Dr. Shear said another reason apremilast is convenient is because it does not require a lengthy assessment process. “Of our oral choices—cyclosporine, methotrexate, [and] acitretin—all require a serious talk about [potential] side effects and [they require conducting] blood tests [before prescribing],” said Dr. Shear. “For methotrexate we are especially following the blood and the liver. For cyclosporine we are especially following the kidneys and high blood pressure, and for acitretin we are looking at lipids and possibly the liver. [However,] we do not have to do any blood work for apremilast.”
He said he would consider adding apremilast to the treatment plan of any patient with psoriasis who is seeking to be almost clear or clear. However, the drug is not approved in children and it should not be taken purposely during pregnancy, though apremilast “is not considered a major risk in pregnancy.”
Dr. Shear said he was open-minded about trying apremilast as a combination therapy. “We just had patients who needed more, and because we are in a medical dermatology group, we are their last resort in Toronto. We said ‘we want to do this but it is a bit innovative. Are you OK with that?’ and they go ‘sure if you can get me clear, I would like to do it'.”
Additional treatment option
“I think it is an exciting twist,” said Dr. Shear. “The development of drugs has been pretty linear. You start with [one of three oral therapies], then you go on to new biologics, and then [might switch to] another biologic—combining biologics has always seemed both expensive and may be dangerous . . . But this is a different approach.
“Patients and [clinicians] expect better control of the inflammation in the [patient’s] body. We want to see not just clear skin, we want to know that there is less inflammation, [which] makes them healthier. We think at the end of the day [this approach is] going to make . . . people healthier.” Dr. Shear said the study provides a “knowledge gap that [clinicians] were interested in” and reassures dermatologists interested in using this treatement technique.
Non-proprietary and brand names of therapies:apremilast (Otezla, Celgene); methotrexate (no branded products); cyclosporine (no branded products); acitretin (Soriatane, Aralez Pharmaceuticals); etanercept (Enbrel, Amgen); adalimumab (Humira, Abbvie); infliximab (Remicade, Janssen); ustekinumab (Stelara, Janssen).
Article first appeared in The Chronicle of Skin & Allergy June 2016 issue