The fixed combination halobetasol and tazarotene topicals significantly reduced psoriasis severity with a favorable safety profile in two phase three studies, shows a study published in the Journal of the American Academy of Dermatology.
Investigational halobetasol/tazarotene (Duobrii, Ortho Dermatologics) combines a potent steroid and topical retinoid. It is the first fixed combination of halobetasol (.01 percent) and tazarotene (.045 percent).
“Both of these drugs, independently, have been shown to be first line therapies for the treatment of plaque psoriasis. We have used them in combination in the past to treat psoriasis because they work by different mechanisms of action,” said Linda Stein Gold, M.D., director, Dermatology of Clinical Research at Henry Ford Health System in Detroit.
This fixed topical is a lotion, applied once daily. Researchers tested halobetasol/tazarotene against each of its individual ingredients, as well as its vehicle in a phase two trial, results of which were published in March 2017 in the Journal of Drugs in Dermatology.
“We found that the combination drug was not just better than the two [individual drugs], but there appeared to have a synergistic effect — meaning that it was even greater than the added effects of the individual ingredients,” Dr. Gold said.
Researchers conducted two multicenter, double-blind, randomized, parallel-group phase three studies. In both studies, 418 subjects, 18 years and older with moderate-to-severe plaque psoriasis received either the combination drug or vehicle. Subjects applied the topical once daily for eight weeks. Researchers assessed outcomes to 12 weeks.
“What we found in each of the phase three trials was that the fixed combination was statistically better than the vehicle at the efficacy endpoint of eight weeks. Then, we did a four-week follow up to see what happened to patients when they go off drug. At the end of eight weeks, we found that the number of patients who got to clear or almost clear, from either moderate or severe disease, was between 35.8 percent and 45.3 percent. This was statistically better than what we saw with vehicle alone,” Dr. Gold says.
There appeared to be a maintenance effect, or a durability of response for up to four additional weeks after the drug was stopped.
In phase three studies, the most common treatment-related adverse events were contact dermatitis, in 6.3 percent, pruritus, in 2.2 percent, and application site pain, in 2.6 percent. There were no reported treatment-related serious adverse events.
How might this work in practice?
The fixed-combination topical is one more tool the psoriasis treatment toolbox.
“It’s certainly appropriate for any patient who has plaque psoriasis. It wouldn’t be appropriate to use in children, because it was only studied in adults. It should not be used in patients who are pregnant. But other than that, it would be appropriate for anybody who has stable plaque psoriasis,” she says.
Once approved, dermatologists might use halobetasol/tazarotene alone or in combination with other psoriasis treatments, depending on patients’ needs. For example, dermatologists could use the combination topical with systemic therapies to treat resistant lesions.
The convenience of a singular fixed treatment could encourage medication adherence amongst patients.
“Compliance is a key factor in a patient getting better. We can prescribe lots of things that we know will work, but if the patient doesn’t use them and use them correctly, they’re not going to have the outcomes that we would expect. I find that simplifying the treatment regimen is really key in getting a patient to use the medication as prescribed. Applying a medication to the body can be very time-consuming. And if you have to do something twice a day it can be a challenge. The fact that this is a once-daily treatment, and it has a nice lotion formulation that’s fairly cosmetically elegant, can help patients to incorporate this treatments into their daily lives,” Dr. Gold said.
Some precautions include educating patients to be careful about sun exposure during treatment, given the drug includes a topical retinoid. Dermatologists should also be careful about using halobetasol/tazarotene in combination with phototherapy. And given the fact that is has a potent steroid, it should not be used on the face or on the skin folds.
Dr. Gold welcomes a new topical amid a sea of biologics and systemic treatment options for psoriasis.
“When you look at our psoriasis patients, the vast majority have more localized disease. Although we have tremendous treatments now for patients with more severe disease and more extensive disease, we tend to ignore, I think, patients who have more localized disease. It’s great to see new treatment options, because, even localized disease, can be just as painful and itchy and just as emotionally devastating,” she said.
The studies were funded by Dow Pharmaceutical Sciences, a division of Valeant Pharmaceuticals North America, makers of Duobrii. Linda Stein Gold, M.D., is an advisor, consultant and speaker for Valeant.
Gold LS, Lebwohl MG, Sugarman JL, et al. “Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of two Phase 3 randomized controlled trials,” JAAD, March 31, 2018. DOI:10.1016/j.jaad.2018.03.040