An alternative way to adopt corticosteroids safely

December 6, 2018

Halobetasol propionate once a week for eight weeks in plaque psoriasis patients was effective, with no adverse events.

Topical corticosteroids are a mainstay in psoriasis treatment, but their long-term use is frowned up due to the risk of a long list of adverse events, such as skin atrophy, telangiectasia, among others. But now, researchers testing a potent topical corticosteroid in patients with moderate to severe psoriasis, may have found a safer, longer term alternative.

Halobetasol propionate lotion has always been considered a super potent corticosterioid, but researchers writing in the Journal of Drugs in Dermatology, say that a 0.01% formulation of halobetasol propionate applied once a day for eight weeks significantly reduced psoriasis lesions with no adverse events. The 0.01% formulation of the lotion (Bryhali by Ortho Dermatologic) was approved the FDA in November.

The researchers, who were led by Lawrence J. Green, M.D., of George Washington University School of Medicine, said that because halobetasol propionate is such a potent treatment, it’s use is usually limited to two to four weeks.

"Conversely, halobetasol 0.01 percent (Bryhali, Bausch Health) is approved for up to eight weeks' use, with once-daily application in a lotion that patients like," said study co-author Jerry Bagel, M.D., of the Psoriasis Treatment Center of Central New Jersey. Although he often prescribes topical creams for moderate-to-severe psoriasis, many patients prefer lotions because they are easy to apply, and less greasy than ointments. “Patients in warmer climates particularly like the fact that lotion, being thinner than cream or ointment, is absorbed into the skin faster. From an aesthetic perspective, an applicability perspective and a compliance perspective, lotions are many patients' topical vehicle of choice."

In short-term trials of halobetasol propionate 0.05 percent, up to 13 percent of patients have experienced application-site adverse events (AEs), most commonly burning/stinging, erythema, dryness or itching, with isolated reports of moderate telangiectasias and mild atrophy. "There were no safety concerns in our two studies using an eight-week once-daily treatment regimen with halobetasol propionate 0.01 percent lotion," wrote Green et al. Application site AEs were reported by fewer than one precent of patients overall, with no reports of folliculitis or atrophy as a result of topical use of halobetasol propionate 0.01 percent lotion. There was one report of telangiectasia that was not considered treatment-related. 

Preclinical research showed that halobetasol propionate 0.01 percent has faster tissue penetration than halobetasol propionate 0.05 percent, and the former delivers more of the total applied dose to the epidermis. “There was limited penetration through the epidermis to the dermis. The less cortisone you get into the deeper layer of the skin, the less atrophy potential, and the less steroid you'll get into the bloodstream," added Dr. Bagel.

The lotion's efficacy appears similar to that reported with halobetasol propionate 0.05 percent, authors added, despite having a lower concentration. The study appeared in Journal of Dermatologic Treatment.

In two separate trials, investigators randomized a total of 430 subjects with moderate-to-severe psoriasis (two to one) to halobetasol propionate 0.01 percent or vehicle. After eight weeks, 38.4 percent and 36.5 percent of patients achieved at least a two-point improvement over baseline on a five-point investigator grading scale and were rated as "clear" or "almost clear."

Body surface area (BSA) measurements decreased by 35 percent. "Let's say you began with around nine percent BSA, and it went down to maybe six percent, with clear or almost clear skin in about 40 percent of patients. Many people using a topical therapy may be happy with that response - not having to go to systemic treatment, which may have more adverse events. They might be happier using a medicine that has proven safety for up to eight weeks, used once daily, compared to other topicals that have to be used twice daily," Dr. Bagel said.

In both studies, mean itch scores dropped more than half a point (on a four-point scale) within two weeks of treatment initiation. "Such reductions boost patient satisfaction, which contributes to long-term compliance," he said.

Dr. Bagel said that he would have liked to see a higher success rate for the lotion. "But you can tell your patient, there's a 40 percent chance you're going to be clear or almost clear in eight weeks, using this medication once daily, as a lotion that absorbs in pretty quickly." Because the medication only needs to be applied once daily, he added, patients can apply it at night and not worry about getting it under their clothes in the morning. "And the safety looks really good."

Halobetasol 0.05 percent has been shown to be an effective treatment of psoriasis in a number of studies, said Dr. Bagel, and in comparative studies with other topical corticosteroids its efficacy was consistently significantly superior. "Now, halobetasol 0.01 percent has been shown to provide comparable efficacy without the two to four weeks, twice-daily application limitations."

DISCLOSURES

The authors (Lin, Martin, Pillai, Israel and Ramakrishna) are employees of Bausch Health. Drs. Green and Cook-Bolden are advisors to Ortho Dermatologics, which contributed to the funding of this study.

REFERENCE
Lawrence J Green MD, Francisco A Kerdel MD, Fran E Cook-Bolden MD, et al. "Safety and Efficacy of a Once-Daily Halobetasol Propionate 0.01 Percent Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of Two Phase Three Randomized Controlled Trials," Journal of Drugs in Dermatology. October 2018.