For patients with mild to moderate plaque psoriasis with 5% to 10% of Body Surface Area (BSA) involvement, treatment options remain limited to topicals or phototherapy. A new study assessed whether apremilast, which is approved to treat moderate to severe psoriasis, could be effective among patients with more mild disease.
Kim Papp, MD, PhD, a dermatologist and president of Probity Medical Research in Ontario, spoke with MD /alert about the results from the ADVANCE trial.
What was the idea behind this study?
As everyone might recall, apremilast was developed for the treatment of moderate to severe plaque psoriasis. And in those studies, it demonstrated definite capacity and ability to treat the moderate to severe plaque psoriasis population. It was also seen, and is perceived to be, a very safe treatment option because there is no requirement for screening for tuberculosis, for example. There’s no need for monitoring. And that makes it a very attractive proposition both for prescribers and for patients.
The biggest void that we have in the treatment of plaque psoriasis is really not so much the moderate to severe group where we have a number of options that are all very competent. What we are looking for and I would say in desperate need of are effective treatment options for patients who have lesser disease burden. And by less, we mean that the surface area of involvement is lower.
So there is a range of patients and probably the majority of patients where topical therapy is not going to be efficient or effective. So patients may have say, 3% or 5% of the body covered and you'd say just on the face of it, ‘Oh well, that's easy.’ Uh, no, because it's not in one patch. It's going to be scattered either in small papules or in small plaques that could be quite widely distributed over the body surface. And that makes topical treatment very inefficient. And phototherapy, of course, is not without its own disadvantages. It may be effective. But it does have disadvantages. And so we're waiting for another option. And that's where apremilast fits into this category because our risk benefit profile is certainly, I think, very evident. We don’t have monitoring. We’re not worried about tuberculosis, we’re not worried about all these other things that may be causes for concern in patients who are treated with other systemic agents. And so this is just a nice way to fill in that gap.
So the study was really just completed to demonstrate the safety and effectiveness in treating this population. And not surprisingly, we find that in fact apremilast is indeed adequately, suitably, appropriately, wonderfully competent at treating patients who have less burden of disease, so that range of patients with, say 5 to 10% BSA of involvement. And the side effect profile is virtually identical to what we see in patients who have more severe disease, and that's largely GI and tolerance issues.
I would also remind everyone that because of the way the adverse effects are coded. It's through the metro code. It's actually taking a very broad funnel of complaints or quotations, adverse events and narrowing them into a very small frame of reference. So for example, when we talk about diarrhea, diarrhea constitutes, for example, a patient who may go from one bowel movement a day or one bowel movement every two days, both of which are in the range of normal, to having a bowel movement every day or two bowel movements a day. It hasn't changed the range of normal, but because there has been a change of frequency and because we as investigators, we are actually soliciting these kinds of changes, if they happen we wanted to know, that's recorded and that will eventually get codified as being diarrhea.
Now, there are patients who truly experience diarrhea in the common sense of the word, for the most part it's not the diarrhea that people would commonly think of as being diarrhea. And similarly when we talk about nausea and vomiting, mild queasiness that may or may not be associated with taking the drug also gets recorded or funneled into this common medical term of nausea and vomiting. So one always has to not take the face value of the terms that are applied. One sometimes has to look behind the scenes to actually get a true sense of what the reality of the situation is. Nonetheless, this is a quick overall arching summary. The study was conducted to give clinicians some guidance as to the effectiveness of apremilast in treating patients with less severe plaque psoriasis. And less severe, in this instance, means patients who have less than 10% BSA of involvement and more than 5% BSA of involvement.
What were your findings?
We found that tolerability was the same as is the case with patients who have more severe disease and those of us who see patients daily are hopeful that we that Amgen will be successful in extending the approval so that we have a better, more efficient, effective therapeutic option for treating patients who are really in high need of effective therapy. And that group of patients who are in high need are just those who have that less severe burden of disease.
Looking forward, where is the field of psoriasis research headed?
Because the therapies are fairly effective and we have a number of options, there’s kind of a saturation point. I don’t think we’ve reached the end of the road. There still will be a number of explorations occurring, and certainly we’re already seeing more exploration of new pathways, such as sonelokimab, and new molecules. So, I don’t think we’ve reached the end of the road. We’re still looking for the Holy Grail because not everybody responds to any of the treatments that we have. Some people are just very resistant. We see a growing number of those cases, whether it’s a selection effect or whatever, we don’t know.
There are also many facets to psoriasis. Psoriasis should be considered as a kind of an amalgam or composite of entities that have significant overlap. We have psoriatic arthritis, for example, and we see that for many of the agents that are effective for plaque psoriasis, they're also effective for psoriatic arthritis. However, they're not uniformly effective. So, one patient may find that in any given patient, they may have their cutaneous manifestation well controlled, but their joints not as well controlled, despite the fact that the drug their on to treat their cutaneous disease is a very confident agent for treating their joint disease, and vice versa. There are patients whose joints are marvelously controlled with the treatment, but their skin is not. And that differential response means that we’re still looking, trying to find something for those individuals. And there are a number of them where we can actually control both of those aspects in a comfortable and efficient manner.
We have another group where we have axial disease and psoriatic axial is a little bit challenging because it’s an overall of typical quotations. Psoriatic arthropathy, which is predominantly an involvement of enthesis, so that’s where the ligaments or tendons actually insert into the bone, which appears to be the fundamental site of action of psoriatic arthritis. And then there’s another condition, which overlaps and may be somewhat related and maybe not. I’m not an expert in that area, but my clinical impression is that they’re not really related, and that’s ankylosing spondylitis. So, there has to be some considerable overlap because ankylosing spondylitis is not commonly present, typically has a specific HLA associations that are not as common or prevalent in the psoriatic population. So, it’s an interesting juxtaposition of these inflammatory arthroses.
Having said that, there are patients who have ankylosing spondylitis as well as axial and peripheral joint involvement with classic psoriatic arthritis. And we don’t have agents that are likewise consistently effective for treating both of those aspects. So, we have molecular entities, IL-17 blockers, for example, appear to be effective, as are TNF blockers effective in treating ankylosing spondylitis and psoriatic arthritis. And yet, we have patients who are on TNF antagonists or IL-17 antagonists who have one or the other of those manifestations well controlled, but not both. And it becomes a challenge. It’s an extraordinary challenge to treat these patients because we’re always trying to balance things. Trying to get the maximal benefit without having to all of a sudden go to polypharmacy. So, there will be ongoing research and at least I would certainly support, encourage ongoing exploration to find new pathways, new molecules that will give us and give our patients a better opportunity to optimize their treatment, both to have effective and uniformly effective as well as safe therapies.
Disclosures: Papp reports consulting, speakers bureau, steering committee and advisory board roles, and research grants and honoraria from Amgen. Papp also reports additional pharmaceutical disclosures unrelated to the study.
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Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.