<p>Recent real-world (RW) evidence highlights the sustained effectiveness of biologic therapies for moderate to severe plaque psoriasis, emphasizing skin clearance, quality-of-life improvements, treatment persistence, and safety in diverse patient populations. Our experts discuss the current state of RW data (RWD) on the treatment of plaque psoriasis with biologics.</p>

When considering RWD, it is important to draw information from larger reliable sources as opposed to smaller sample sets. When I formulate an opinion on how RWD compare with clinical trial data, I look at larger registries and, to some extent, reasonably rigorous claims database analyses. Recent patterns in RWD are different from what we were seeing 5 to 10 years ago because of the medication classes that we currently use.

<br>

In RW analyses, the efficacy of IL-23 and IL-17 inhibitors generally follow more closely with what is seen in clinical trials. However, it is important to recognize that RW treatment happens in a less monitored environment, and, even in the best registries, patients tend to stop treatment more often than they would in a clinical trial setting. In open-label extension studies of clinical trials, we tend to see a horizontal retention of efficacy over time, but, in the RW setting, we see an erosion of response as patients “fall off” the drug. This can be due to insurance reasons, poor adherence, pathophysiologic changes of the patient’s psoriasis (making it less responsive to the current therapy’s mechanism of action), adverse events, or poor tolerability. Therefore, the durability of response invariably looks a little worse with all drugs in the RW setting despite consistent observations about upfront efficacy. There is a level of unpredictability regarding follow-up in the RW setting vs what we see in clinical trials.

<br>

RW evidence suggests a good retention of efficacy for IL-23 and IL-17 inhibitors, although it is less than what was seen in clinical trials, and the safety profiles may also appear less clean than what is seen in clinical trials. Again, this may be because clinical trials typically enroll healthier patients, while RW environments may include more patients with comorbidities and polypharmacy. Perhaps patients who would never get into clinical trials are now being measured, which may lead to more adverse events being noted.

Real life is chaotic and messy. The cadence of the visits in clinical trials is often unrealistic in terms of what we do in our own practice. Clinical trials serve their purpose for drug approval, and, ideally, data from a phase 3 trial would be generalizable across all patients. However, we know that this may not be realistic because trials have a contained and limited cohort. And, while there have been efforts to improve this, the diversity of clinical trial patient populations does not necessarily mirror who is going to walk through your door. At the end of the day, these studies are meant to show that an agent is effective and safe for a certain period, but clinical trial data can be difficult to translate to the RW setting.

<br>

Therefore, I appreciate the information we can get from RWD. To Dr Strober’s point, patients in RW studies are often sicker, they may face unique challenges that are not considered or selected for/against by a formalized clinic study protocol, and they may even—or will—miss doses of their medication. These are things that would not be captured in a clinical trial, and this is information we are hungry for.

<br>

Finally, the numbers reported in clinical trials do not necessarily correlate with how happy our patients will be on a given treatment. I find that many patients with plaque psoriasis do not want to tolerate visible disease over even a 0.01% body surface area. A drug achieving a high level of patients with Psoriasis Area and Severity Index (PASI) scores of 90 in a clinical trial sounds amazing, but this result may not satisfy the patient. The clinical studies do not capture that. I love RWD, and we definitely need more of it.

I agree with everything that has been said by my colleagues. As Dr Strober mentioned, we are seeing longer survivability with these newer biologic agents. People are staying on these drugs longer, and we assume that this equates to efficacy and the fact that they are happy. I agree with Dr Friedman that patients with plaque psoriasis have a very low threshold for feeling that their drug has stopped working. They may come into the clinic really upset when a psoriatic plaque comes back.

<br>

I think it is a good sign that these patients are staying on the drugs longer. I see this reflected in my clinical practice as well. I have noticed over the last 3 to 4 years that I have been switching drugs a lot less. In the past, my patients and I would often have the conversation about staying on treatment, switching, or adding another agent. These days, I am having those conversations less often. That is very positive because it gives me time to talk about other things with my patients. We can better screen them for psoriatic arthritis, we can talk about their comorbidities, and we can make sure that they are seeing their primary care physicians. This is a real advantage of some of the newer therapies.