Long-Term Safety and Efficacy of Roflumilast Cream in Plaque Psoriasis

Leon Kircik, MD: First, why don’t we look at the study design and then we’ll discuss the safety and efficacy. Here we had 2 different cohorts. Originally, the study inclusion criteria were a diagnosis of at least mild plaque psoriasis, but it could have been mild, moderate, or severe. An age requirement of 18 years of age and above. The body surface area requirement was anywhere from 2% to 20% body surface area. We had a randomization period. The first 12 weeks people were randomized into…the vehicle once a day, roflumilast 0.15% once a day and roflumilast 0.3% cream once a day. After that, those patients were rolled over into the open-label, long-term study that was cohort 1.

Then we had the cohort 2 people that came from another study that had basically very similar inclusion criteria. In this case, they had 2% to 25% body surface area and again, age 18 years and above, and they had to have at least mild plaque psoriasis for at least 6 months. So the body surface area requirement was a little bit different here. They were also using roflumilast 0.3% once a day, but those were the fresh people that this was the first study they were in. That study was over 2 weeks. The primary end point was safety, which looked at the occurrence of treatment emergent adverse events, or the occurrence of serious adverse events. The secondary end points—of course when the sponsor spends the money doing an open-label, long-term study, they’re going to look at efficacy, as well. That was clear or almost clear overall. But also, as I mentioned earlier, intertriginous psoriasis IGA [Investigator’s Global Assessment] was looked at [and found to be] clear or almost clear. PASI, which is psoriasis area severity index, as well as the improvement in body surface area, were also considered.

Safety is very important for us as dermatology providers. Let’s just touch upon a couple of points on that. What we saw is on the long-term data, we have about 50% any adverse events, but that doesn’t mean those are related to the study drug. We do clinical studies all the time and unfortunately, or fortunately, whatever happens to the patient as an adverse event, we have to report that to the agency. That’s where that 50% number comes down. Out of those 50%, 94% were mild to moderate and there were no SAEs, meaning serious adverse events or deaths that were related to the study drug. That’s important. But, most importantly, there are 2 things when you do a clinical study when it comes to safety. Number 1, is anybody dropping off the study? Think about it, when you’re giving the patients a free drug and when you’re paying them to stay in the study, why would they drop out? So here, that number is quite low. It was 3.9% of all the patients from the pooled data that dropped out of the study due to adverse events. So that’s good news. Number 2 is, that when we think about the topical treatment, we have to consider what I call the local adverse event profile, and the biggest one is irritation. With this drug, more than 90% of the patients did not have any evidence of irritation. What does that mean? Less than 3% of all the patients had irritation, which is quite a very low number. I think those are important parameters that we evaluate safety when we are looking at a clinical trial.

I think the long-term efficacy is important because we are able to see if the patients are maintaining their efficacy over a long-term period that they achieved during the first treatment period. So, this is an important question when you are treating a chronic disease such as psoriasis. Despite the fact that I said we have so many new treatment options—we have 11 biologics, a bunch of new orals and topicals—we don’t have a cure yet. We do not have a cure for psoriasis, which makes it a chronic disease, which makes its long-term efficacy and safety very important and very relevant to both providers, as we treat the disease, but also to the patients. So, when we look at those numbers, there were 2 cohorts that we basically enrolled them in the long-term study and we have data up to week 64 from cohort 1.

The number who maintained clear or almost clear was 35% and cohort 2 was 40% at week 64. Another way of looking at it is, if you start 10 patients on this drug, when they reach at week 12 with clear or almost clear status, which is a 2 grade improvement, at week 64 almost 3 to 4 of them still will be maintaining that status, which is more than a year. So that, I think, summarizes those important aspects of efficacy and safety for this drug over the long term.

Transcript edited for clarity