Dr Armstrong on Oral Therapies for Psoriasis

In this podcast, April Armstrong, MD, reviews the latest updates in oral therapies for the treatment of psoriasis, and discusses why having these options is important for patients.

Dr Armstrong is the associate dean of clinical research and professor of dermatology as well as a dermatologist with Keck Medicine of USC in Los Angeles.

Transcript

Melissa: Hello, everyone. I’m Melissa, Associate Editor of The Dermatologist and host of this podcast. Today, we’ll be speaking with Dr April Armstrong about updates in oral molecules for the treatment of psoriasis, which she presented at virtual Fall Clinical meeting.

Dr Armstrong is the Associate Dean of Clinical Research and Professor of Dermatology at the University of Southern California Keck School of Medicine in Los Angeles. Thank you for joining us today, Dr Armstrong. What current oral options are available for patients with psoriasis?

Dr April Armstrong: The current treatments for oral therapies for patients with psoriasis include methotrexate, apremilast, cyclosporine, and acitretin. Apremilast is one of the newer therapies for oral treatment for psoriasis, and it is typically dosed as 30 mg twice daily. It is thought that apremilast has good efficacy in patients with psoriasis as well as psoriatic arthritis.

One of the key developments for apremilast in the past year is its approval for oral ulcers ulcers that’s associated with Behcet’s disease, which I think is actually quite an advancement for our field as the new therapy for Behcet’s because, as we know, it’s oftentimes a orphan disease without a lot of good therapies.

I would say the latest literature with regards to apremilast include that if apremilast is introduced early on the onset of moderate psoriasis and if apremilast is tried especially in bio-naÔve patients with less comorbidities, it tends to do better, meaning that patients tend to stay on apremilast a little bit more.

There are also observations showing that apremilast improved nail psoriasis in some patients. One of the latest publications on apremilast is looking at combination of apremilast with oral retinoids and show that that combination can be synergistic and increase efficacy.

Now methotrexate is one of our really workhorses of oral therapies to treat psoriasis prior to the advent of biologics. The update for methotrexate for the last year is really liver hepatotoxicity monitoring.

As many of us know, that liver biopsy has really gone to the wayside at this time, that non-invasive methods of imaging and following people’s fibrosis have becoming really the more standard way of following our patients who are on methotrexate for a longer term.

One of the things, for example, elastography, is essentially a FibroScan, is increasingly to be used for these patients and is preferred over liver biopsy.

With regards to methotrexate use in COVID, just a few other updates is that there’s no increased frequency of risk of respiratory viral events that have been associated with methotrexate compared to those who did not use methotrexate.

A lot of that data came from the rheumatology literature. There’s even some data showing that in vitro, methotrexate may inhibit SARS-CoV2 that viral replication.

For cyclosporine, I think it continues to be a good option for people who are what I consider crisis patients or patients who have, for example, erythrodermic psoriasis or severe pustular psoriasis that we want to get under control quickly but as a bridge to a long-term therapy such as a biologic therapy.

Cyclosporine, just as a reminder for our listeners, if you do want to use cyclosporine to treat severe psoriasis, you want to start them on an adequate dose. Typically, the recommendation is starting cyclosporine at four to five mg per kg per day. We calculate that dosage, and you divided into a b.i.d. dosing.

When the patient is doing well, we typically taper cyclosporine. We typically advise against stopping cyclosporine abruptly.

Lastly, for acitretin, I would say there’s not a lot of new things regarding acitretin in psoriasis other than it continues to be used in some patients for palmoplantar psoriasis and pustular psoriasis. The median dose for patients with those conditions using acitretin is about 25 mg per day.

Melissa: So what are some new options that are in the pipeline?

Dr Armstrong: When we think about the nearest therapies that are in the pipeline, one really stands out, and that is deucravacitinib. Deucravacitinib is a Tyk2 inhibitor. In fact, when I was presenting at the Fall Clinical, we only had phase 2 data. Since the Fall Clinical, the topline results were revealed just last week.

So this is very exciting. They’ve completed their phase 3 trials. Deucravacitinib is an oral selective small-molecule Tyk2 inhibitor. It’s unique in that it actually binds to the regulatory domain of Tyk2. That domain’s typically not as shared by JAK kinases. As a result, the mechanism of action is thought to be more selective.

What we found in the phase 2 results was that deucravacitinib had a robust efficacy against placebo and, with regards to the topline results that were released, that deucravacitinib did achieve its primary endpoint in the phase 3 studies.

Melissa: Why is having these oral options important for patients?

Dr Armstrong: For our patients with psoriasis, I think that it is good to have various options because they have different preferences of how they would like to take medications. For some people, for example, injections work fine. For other people, they may prefer oral options.

I think oral options is also important because it can lend certain degree of flexibility. Oftentimes when we think about small molecules, it is typically something that we don’t worry about if we stop the medication, whether the patient is going to develop anti-drug antibody. That typically doesn’t happen because it’s a small molecule.

Therefore having the oral options is very important because patients can go on and, when you need to, go off a little bit more flexibly than, let’s say, with biologics. But probably most importantly, many of our patients prefer oral options over needles. So having oral options, I think, is always very nice for them.

One thing I did want to mention is that there is a difference with regards to frequency of administration for oral therapies versus biologics. Typically, oral medications have to be taken daily, if not twice a day, whereas for biologics, as we know for some of our IL-23 biologics, they can be taken as infrequently as once every three months.

So I typically talk about not only safety/efficacy with patients, but importantly, with regards to dosing administration and with regards to the convenience, I also tell them a little bit about the frequency so that they can really evaluate these options and hopefully we can come up with a shared decision that would be really satisfactory for the patient and for myself.

Melissa: What key takeaways would you like to leave with our audience?

Dr Armstrong: The key takeaways that I would like to leave with our audience is that we have a number of oral therapies that are still available for patients with psoriasis, and some of them are also effective for psoriatic arthritis.

So when we consider the different treatment options for patients with psoriasis, I would say in addition to the biologics that we now oftentimes think about, oral therapies are another option.

One thing about oral therapies, as I mentioned earlier, is that they may be a little bit more flexible with regards to on- and off-drug.

In addition to that, what’s exciting is that we have something in the pipeline, a Tyk2 inhibitor that is a pretty selective oral Tyk2 inhibitor that has efficacy that’s robust at the biologic level, and it is something I believe will really add to the armamentarium of therapies for our psoriasis patients.

Melissa: Thank you for listening. If you have any questions or comments, please submit them in the feedback box below.