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Oral roflumilast (Daliresp) may be an inexpensive and effective treatment option for patients with psoriasis who are candidates for systemic therapy, according to research presented at the American Academy of Dermatology (AAD) annual meeting.

MedPage Today brought together three expert leaders in the field: moderator , a dermatologist and clinical researcher from Peterborough, Ontario, is joined by , a dermatologist and director of clinical research at Southern California Dermatology in Orange County, and , founder of FACET Dermatology in Toronto, for a virtual roundtable discussion. This last of four exclusive episodes focuses on the results of a phase II randomized trial evaluating the efficacy and safety of oral roflumilast in adults with moderate-to-severe plaque psoriasis.

Following is a transcript of their remarks:

Gooderham: Hello, I'm Melinda Gooderham. I'm a dermatologist and clinical researcher from Peterborough, Ontario, at the SKiN Centre for Dermatology and an assistant professor at Queen's University. I wanted to welcome you to this roundtable discussion on top news from AAD 2023, and I'm delighted to have with me today, Dr. Geeta Yadav, who is the founder and medical director at FACET Dermatology in Toronto and a lecturer at the University of Toronto, and Dr. Jennifer Soung, who is the director of clinical research at Southern California Dermatology and is on the clinical faculty at Harbor-UCLA.

All right, so moving on that same theme of PDE4 inhibition, there was another investigator-initiated poster presented at the late-breakers. The efficacy and safety of oral roflumilast in the treatment of moderate-to-severe psoriasis, a randomized, double-blinded, placebo-controlled trial, .

This was done in Denmark without any industry funding. So that was an interesting one for the late breakers, it's good for them. So they looked at roflumilast 500 mcg once a day versus placebo for the first 12 weeks. They had 23 patients randomized to each arm. At week 12, the placebo patients rolled over to receive open-label oral roflumilast, the same dose 500 mcg once a day.

So total 24 week study and eligibility criteria were quite similar to any other psoriasis clinical trial with adults. And PASI [Psoriasis Area and Severity Index], BSA [body surface area] similar to the other phase III programs. And they had some baseline characteristics, again that were quite typical -- average age late 30s, two-thirds to three-quarters that were male there in Denmark. So they had 100% Caucasian patients. Their baseline characteristics, the median PASI was about 10, BSA 10 to 14%, sPGA [static Physician's Global Assessment] of 2, with a significant impact on DLQI [Dermatology Life Quality Index] about 9 to 10.

So what they found at the 12-week mark and the primary endpoint being PASI 75 at week 12 was 35% of roflumilast patients achieving the PASI 75 compared to 0%. So there was like no placebo response in that first 12 weeks. Placebo patients then switched over and in 12 weeks they had a 39% PASI 75 rate. So fairly consistent results, and also consistent to what we have seen with other PDE4 inhibitors, such as apremilast [Otezla], in that sort of 30 to 40% range of PASI 75, although it was week 16 with apremilast.

So we saw a nice mean change from baseline and PASI in the drug group. The placebo group had no reduction until they were rolled over onto the drug. And you could see the drug worked well across groups, and even in PASI 90, one-fifth of patients were able to achieve a PASI 90 in this study.

So for tolerability, we know PDE4, as we just discussed, gastrointestinal intolerance seems to be one of the main issues. And here we did see some high rates of diarrhea.

Dr. Yadav, you were mentioning before about the importance of safety and tolerability. What do you think about this AE [adverse event] chart?

Yadav: Yeah, it does make me mindful that it's not just the safety story, it's also the tolerability story. And I think, again, we take some of these things a little bit for granted with the agents that we've had available to our patients in the last decade-plus. And so as we move into adding more therapeutics into our toolbox, I think safety is definitely where the focus is going to be in the next coming years. But also tolerability as we try to kind of broaden the target and find the balance because there's no point in having a drug that's very safe but totally intolerable.

And weirdly when we look at the numbers here, the placebo group had very high rates of diarrhea, like 30%. So it is comparable to the treatment arm. However, it's not sort of, to me, consistent with what I'd expect in like baseline population numbers. And maybe that's just because the number of people in this study was quite small, so maybe it's not reflective.

Gooderham: Yeah, it's interesting because there was 0% efficacy in the placebo, but they had the same AEs. Dr. Soung, what did you think about this poster, or presentation?

Soung: You know, I was really curious because we certainly have many treatments for psoriasis that are highly effective but are expensive. So what makes oral roflumilast here unique is that, one, it's already internationally approved for use in severe COPD [chronic obstructive pulmonary disease]. So we have a history of safety that's established not in our population, but a history of safety. And there are generic versions available in the U.S. So it can be a very inexpensive option, especially for our patients who are non-insured or who are on Medicare and can't afford other treatment options.

So, I'm really curious and happy to see that someone here is exploring oral roflumilast in our psoriasis patients.

Gooderham: Yeah, no, I think that was great. I believe Professor [Alexander] Egeberg said it's cheaper than a Starbucks a day. So I think in Denmark they have the same issues with accessibility and so it is nice to have a medication that can be more affordable for some patients, like, as you say, who are maybe uninsured and don't have access to some other treatment. So that's great.

Tolerability always an issue. We've been dealing with it for years with apremilast. So, many patients take it with no problem, they have no tolerability issues. So I think it's great and hats off to them for going and doing that investigator-initiated study. That's really great.

So I wanted to thank both of you so much again in your crazy busy schedules at the AAD this year to take some time and talk about these late-breaker sessions. I think it's really an exciting time right now, for awhile now in dermatology, with new mechanisms of action, oral therapies, in addition to our biologic therapies. So thanks very much to both of you for taking the time to talk about these today.

Soung: Always a pleasure.

Yadav: Likewise. Thank you.

Watch episode one here: Trial of Novel TYK2 Inhibitor Hits Its Endpoint in Plaque Psoriasis

Watch episode two here: Switch to IL-23 Blocker Yields Deep Responses in Recalcitrant Plaque Psoriasis

Watch episode three here: Orismilast Clears Skin in Moderate-to-Severe Psoriasis

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