Opinion
Video
Head-to-Head Studies for Plaque Psoriasis Therapies
Expert dermatologists highlight the benefits of head-to-head trials for various agents for the management of plaque psoriasis and review the top-line results of a study comparing risankizumab and apremilast.
Bruce Strober, MD, PhD, FAAD: Jennifer, we have a lot of head-to-head studies between IL-23 inhibitors and other medications with different mechanisms of action. What are your take-home messages about these head-to-head studies, and how did you apply them to your approach to patients with psoriasis?
Jennifer Soung, MD: I like looking at the meta-analyses. Many of our clinical trials have similar inclusion criteria, and for plaque psoriasis, a lot of the studies have been designed in a similar way, which is nice because we may not be able to do a head-to-head [study for] every single drug that we want. That would be expensive, so it’s nice to be able to use statistics to calculate it. That’s my favorite thing to look at when we’re comparing drugs because the question is, [because] we have so many different options, “How are you going to choose?” When it boils down to just looking at skin clearance rates, then we see that our IL-23s are at the top, whether you’re looking at PASI [psoriasis area and severity index] 75 or PASI 90. You can look at it short term, [such as] around week 12 to week 16, or longer term at around 48 or 52 weeks, so it’s a combination of our clinical experience as well as looking at some of these statistics to help us sort out these head-to-head situations that we’re thinking in our mind: “OK, am I going to choose this drug vs the other drug?” One of my favorite ways to look at the data is how Andy Blauvelt, [MD, MBA,] looked at [them] recently in another meta-analysis: looking at cumulative clinical benefits. [It’s] a combination of comparing all these different systemic drugs, biologics and orals, and looking at the speed of onset and response over time. You’re not looking at 1 point in response or skin clearance rates. We’re wanting to understand, and we want patients to get clear and stay clear. So that’s another great way of looking at or indirectly comparing these drugs. And we see that the [IL-]23s are at the top.
Benjamin Lockshin, MD, FAAD: Jen makes a good point. I love seeing head-to-head studies where you get to look at 3 different components of comparing drugs. You get to look at the efficacy. It’s always fun to beat the snake out of another drug if you’re doing a head-to-head study. The second thing is it validates the data, because if the comparator drug [data] look similar to their own phase 3 data, it makes the numbers of that study drug look even more impactful. And you get to compare safety in a head-to-head blinded manner as well. All those things taken together add a lot of value in choosing medications and looking at them across classes in terms of how they pair up. And I agree with Jen that the IL-23 agents jump to the top in both categories in terms of safety and efficacy. And it’s very rare that we’re able to continue to see higher levels of skin clearance without sacrificing that safety.
Bruce Strober, MD, PhD, FAAD: Another setting where we get information is registry studies and large databases that assess comparative efficacy between the various products. And again, in real-world settings and registries, we see IL-23 inhibitors have excellent durability over the long haul. Patients stay on them longer than other mechanisms of action. And this is supported by multiple settings, different countries, different registries arriving at the same conclusion about IL-23s and their durability. But we need to put it all together. [For] head-to-head studies done by [pharmaceutical companies], which are over 52 weeks, which drug is better? And there can be a placebo group in there. [We have] meta-analyses, which are excellent, but especially meta-analyses that are done independently from each other and still come to the same conclusion. We do have [those]. It’s amazing how the meta-analyses are aligning, meaning that their methodologies, although slightly different, are arriving at the same answers. And finally, [we have] real-world analyses through registries and databases from countries. All this gives us, as a specialty, more than other specialties in terms of how we can compare our therapeutics. There shouldn’t be a mystery to the average provider as to which drug has the best batting average. When it’s up at the plate, what’s the likely success for that drug? What’s the probability? We shouldn’t have any doubts in our minds about these issues because of the enormous amount of data out there in many settings.
Recently, there was a study done comparing risankizumab to apremilast. And it was measuring not only efficacy but also patient preference and quality-of-life metrics. Ben, I know you alluded to the study earlier. Could you go through the top-line results from that study?
Benjamin Lockshin, MD, FAAD: The impulse study was an investigator-blinded study where patients received risankizumab or apremilast. And the top-line results were [that] the patients receiving risankizumab did dramatically better in terms of achieving PASI 90 scores compared with [those taking] apremilast. No one would even question that. Where the money lies is [that] the [results from] patient satisfaction surveys and the treatment satisfaction questionnaire for medications that were employed during this study showed that [for] every question, the response rates were significantly higher in terms of patient satisfaction on risankizumab vs apremilast. Moreover, the number of patients who continued through all segments of the study in the risankizumab group was dramatically higher than what we saw with apremilast, showing that patient adherence was better, patient happiness was better, and the objective end points that we used for most of our studies were greater. This was focusing on a patient population whom we generally treat in our clinics, which is a patient group [with] moderate [disease]. All the patients [had] PGA3 [pepsinogen A3] [disease], which is moderate disease. Their body surface area was about half of what we saw in most of the pivotal phase 3 studies for all the biologics as well as [for] the PASI score, which was around 14.5 as opposed to about 26 that we see in [findings from] most of these clinical trials.
Bruce Strober, MD, PhD, FAAD: That blows up the notion that an oral therapy is going to be more preferred than an injectable therapy. There’s no doubt, and it depends on the medications we’re looking at, but a highly efficacious injectable therapy is going to be preferred in its low frequency of use of [every] 12 weeks and be preferred over an oral medicine that’s twice daily and lower in the efficacy hierarchy.
Benjamin Lockshin, MD, FAAD: You mentioned something earlier in terms of oral vs biologic agents in respect that the tolerability of risankizumab, of an IL-23 agent, is so much greater on a day-to-day basis compared with these oral small-molecule medications. We are in a very strange field where a lot of times patients in some of these clinics are steering the ship. You don’t see this in endocrinology or oncology, where the patient [says], “My blood sugar [level] is 600, but I’ll go on that form and I don’t want an injectable.” That doesn’t happen, but I’m surprised when I talk to a number of dermatologists and APPs [advanced practice providers] in dermatology who say that the patient came in and wanted an oral option. We need to take it personally and say we want to give you the option that’s most appropriate for your disease state based on efficacy and tolerability. [Findings from] this study highlight the fact that risankizumab is a much better product than apremilast in all realms.
Bruce Strober, MD, PhD, FAAD: Jennifer, anything to add to that conversation [on] that study?
Jennifer Soung, MD: One of the goals is to show not that we can compare safety head to head but [that] overall safety was what we have seen in [findings from] their pivotal phase 3 studies, so it doesn’t mean that an oral is necessarily safer than a biologic.
Bruce Strober, MD, PhD, FAAD: Absolutely. [For] this study, some people ridicule it because it’s like David vs Goliath, but on the other hand, what they were looking at was dispelling these notions that the oral therapeutic is going to be more acceptable to a patient population. In fact, that concept was purely refuted by the treatment satisfaction questionnaires and the DLQI [Dermatology Life Quality Index] assessments. Patients are happy to get injectable biological therapy. If it’s working, doesn’t cause adverse effects, [and] doesn’t require monitoring, they feel better on it. As providers, how we view therapeutics is how our patients do. You [can] impart to your patient this is no big deal; it’s an injection. It’s not chemotherapy; it’s a medicine that’s given as a subcutaneous injection, but it’s still one that you should feel comfortable with for all the following reasons.
Benjamin Lockshin, MD, FAAD: And one thing that’s overshadowed in [findings from] that study is the safety comparison between both arms and serious infections we’re seeing at a higher rate with apremilast as well as many other adverse events, and we’re leaning more toward apremilast than risankizumab. And many providers choose apremilast because some of the patients walk in and want it and think it’s the safest option. And there’s a paradigm shift, as you were saying, which is in understanding that these biologic therapies are heat-seeking missiles. They’re targeted agents with very little collateral damage and minimal safety signals that fall into the rare and scary or the common.
Bruce Strober, MD, PhD, FAAD: And that’s why we can use them earlier and use them in a population [with] more moderate [disease], and we don’t have to step through therapies to get to them. They’re remarkable, revolutionarily effective medicines that are well tolerated. And who doesn’t want a patient on that type of medicine? [They are] predictable.
Transcript is AI generated and edited for clarity and readability.
