Treating Plaque Psoriasis: Insights on HP/TAZ Lotion

In May 2021, a phase 3 open label study¹ highlighted the long-term efficacy and safety profile of halobetasol propionate 0.01%/tazarotene 0.045% lotion (HP/TAZ) for treating moderate to severe plaque psoriasis.

“Now, the rationale behind this formulation is that halobetasol is a very effective anti-inflammatory product, but it has the side effects of a strong steroid such as cutaneous atrophy. On the other hand, tazarotene is a retinoid which is quite irritating, but it protects against cutaneous atrophy,” said Mark Lebwohl, MD, dean for clinical therapeutics and a professor of dermatology at Icahn School of Medicine at Mount Sinai in New York City, NY.

“This is such a logical formulation because the halobetasol suppresses the irritation that you get from the tazarotene, and the tazarotene prevents the atrophy that you get from the halobetasol. This was a logical combination that, indeed, did what was promised and worked quite well.”

Dr Lebwohl is chairman emeritus of the medical board in the National Psoriasis Foundation and founding editor of Psoriasis Forum, now the Journal of Psoriasis and Psoriatic Arthritis. With this he has authored or co-authored more than 600 peer-reviewed articles and numerous textbooks, chapters, and abstracts. He joined The Dermatologist to discuss his insights into HP/TAZ lotion when treating moderate to severe plaque psoriasis.

Can you share with us the data from the previous two phase 3 randomized controlled trials² on the safety and efficacy of HP/TAZ?
When compared to halobetasol alone, tazarotene alone, or its vehicle, the fixed combination of HP/TAZ as a topical therapy achieved 2 grades of improvement with clear and almost clear skin, on an Investigator Global Assessment, more often. Not only was there a statistically significant benefit in favor of the combination, but more than half the patients achieved that 2-grade improvement at week 8. Remarkably, when those patients were examined at week 12, about 40% were still clear or almost clear. This was not only a substantial improvement, but a durable response.

Several other parameters were examined. The one that we're usually most concerned about is plaque elevation as a marker for psoriasis. Actually, when utilizing HP/TAZ in terms of plaque elevation, this was where the greatest benefit was achieved. In fact, if you look at the side effects in this study, the HP/TAZ combination had a suppression of local skin irritation, itching, dryness, and burning that we know to expect with tazarotene. In particular, dryness and itching were suppressed by that combination.

Also, HP/TAZ is very comparable to our strongest steroids. The efficacy is excellent, but of course instead of it being our strongest steroids, we have the retinoid in there protecting against steroid side effects.

The frequency and severity of local skin reactions was extremely low. On a 0 to 3 scale, the mean was always below 1.5. After week 2 it was below 1.0, and the frequency of local skin reactions was less than the vehicle.

How can the durability of the HP/TAZ lotion affect patient quality of life?
I think patients have a sense of security. They've gone through 8 weeks of applying this medication. It's applied only once a day. At the end of 8 weeks, they are less nervous about their psoriasis coming back because they know that they get a durable response from the combination.

In your May 2021 study, how does the long-term safety (W52) compare with short-term (W8)?
In this study HP/TAZ was given once daily for 8 weeks. Then, as needed, in 4-week intervals for up to a year, depending on whether they were clear or almost clear, the maximum continuous exposure was 24 weeks. Within the first 8 weeks, 54.4% of patients achieve treatment success. Over half of those patients did not require treatment for another 4 weeks. In fact, 6.6% did not require any retreatment for the whole year. Among the participants for the full 52 weeks, 77.5% maintain less than 5% body surface area while they're on the treatment.

There was marked improvement in every parameter of PsO, but also in the severity of itching, dryness, burning, or stinging over the study course. Side effects attributed to HP/TAZ tended to subside over the treatment course. Bear in mind that patients who dropped out because of side effects would not be in the study.

The point is that a high proportion of patients cleared, a high proportion didn't need or went for long periods without needing retreatment, and the side effect profile was very benign compared to halobetasol alone or tazarotene alone.

With the HP/TAZ lotion added as another option, how has the treatment of psoriasis evolved over time?
More and more we’re using combination therapy. I would say the one thing that has gotten in the way of combination therapy has been access through insurance companies. Of course, a lot of our colleagues need to understand that the insurance companies, through their pharmacy benefit managers, try to demand payments from pharmaceutical companies that that would raise the cost of all drugs.

This combination of halobetasol and tazarotene is reasonably priced. With commercial insurance, it can be purchased for $25; without insurance, it’s $65. Larger pharmacies such as CVS or Walgreens may not honor the discounted price, but here in Manhattan, there are a couple of pharmacies that will honor discounts and coupons.

Is there anything else notable about moderate to severe plaque psoriasis or HP/TAZ lotion that you would like to share?
I think that we are at a time when we have better and better treatments for psoriasis, both systemically and topically. The main barrier has been insurance company hurdles.

As I explained, the cost of this is very reasonable, so I encourage my colleagues to take advantage of the availability of less expensive topical therapies that don't have to be subject to the hurdles set up by insurance companies.

References
1. Lebwohl MG, Stein Gold L, Papp K, et al. Long-term safety and efficacy of a fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis: phase 3 open-label study. J Eur Acad Dermatol Venereol. 2021;35(5):1152-1160. doi:10.1111/jdv.17113

2. Gold LS, Lebwohl MG, Sugarman JL, et al. Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: results of 2 phase 3 randomized controlled trials. J Am Acad Dermatol. 2018;79(2):287-293. doi:10.1016/j.jaad.2018.03.040