expert roundtables

Moving Toward More Precisely Targeted Therapies for Plaque Psoriasis

by Steven R. Feldman, MD, PhD; Joel M. Gelfand, MD, MSCE; and Alice B. Gottlieb, MD, PhD

Overview

With increasing knowledge of the complexity of the immune system, more precisely targeted therapies have become available for the treatment of moderate to severe plaque psoriasis. Such therapies continue to have a profound impact on psoriasis patient care.

Q:

How has the availability of targeted therapies for plaque psoriasis impacted patient care?

Joel M. Gelfand, MD, MSCE

Professor of Dermatology and Epidemiology
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

This is the arc of progress in psoriasis: what people thought was not possible, becomes possible. We need to keep on pushing the envelope to achieve better outcomes for our patients.”

Joel M. Gelfand, MD, MSCE

Ultimately, our goal is to choose a therapy that is going to work and work well in the long-term, as long-term efficacy is a major advantage of any treatment. And that is why the more clinically relevant question is not what do the results look like at week 12, but what is happening at week 52 and beyond? The next phase of research in the psoriatic disease community likely needs to take a page out of the cardiovascular community book and look at 5-year outcomes. We should randomize patients to different strategies (ie, a tumor necrosis factor [TNF] strategy, an interleukin-17 [IL-17] strategy, and an IL-23 strategy) to find out which group does the best over a period of 5 years, as that would be more relevant to the patient’s experience than finding out how the groups compare at week 12.

Now, obviously, it is more difficult to conduct that type of trial, and it requires more resources. However, there was a time when you would have been called “crazy” if you had told someone that you wanted to do a head-to-head trial in psoriasis. Even further, if you had insisted that a head-to-head trial in psoriasis be conducted for a full year, again, you may have received looks of disbelief. This is the arc of progress in psoriasis: what people thought was not possible, becomes possible. We need to keep on pushing the envelope to achieve better outcomes for our patients.

Some patients are told by their doctors that they should avoid biologics because they might have serious adverse effects. I tell my patients with psoriasis that the TNF, IL-17, and IL-23 inhibitors are remarkably safe and that it is rare for me to have to stop them due to a side effect. Based on product labeling, biologics that target IL-17 or IL-23 may be safer than those that target TNF; however, in head-to-heads trials, we have not seen a differentiation of these products based on safety. Patients often prefer the IL-23 blockers because they require fewer injections and they currently have the fewest safety warnings.

Steven R. Feldman, MD, PhD

Professor of Dermatology, Pathology, and Social Sciences & Health Policy
Wake Forest School of Medicine
Winston-Salem, NC 

You might think that highly effective, sophisticated, injectable therapies would be taken on time and without fail, but this is not always true. So, anything we can do to improve adherence or reduce the dosing burden is helpful, in my view.”

Steven R. Feldman, MD, PhD

Before the availability of etanercept, which I believe is the weakest of the TNF inhibitors that we use for psoriasis, we had drugs such as methotrexate and cyclosporine, and we had people suffering with terrible psoriasis even on treatment. At that time, a colleague and I published that clearing psoriasis is just an unrealistic expectation, and then TNF inhibitors came along and just revolutionized treatment. And the treatments have become so much better, with high proportions of patients achieving excellent therapeutic responses, that, in certain ways, patient selection for personalized treatment has become less important. That is, our treatments work so well in the vast majority of cases that we do not have the need to perform predictive testing to see who is going to respond to which therapy.

However, adherence is a topic that is near and dear to my heart and one that is relevant to any therapy you might be considering, including biologics. The most common reason for treatment failure in dermatology may be poor adherence. You might think that highly effective, sophisticated, injectable therapies would be taken on time and without fail, but this is not always true. So, anything we can do to improve adherence or reduce the dosing burden is helpful, in my view.

Alice B. Gottlieb, MD, PhD

Clinical Professor and Medical Director
Mount Sinai Beth Israel Hospital
Department of Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY

“Patients today might be switched from one biologic to another because of primary or secondary treatment failure, but rotational therapy is no longer the paradigm, and I think that biologics have dramatically altered clinical practice in this way.”

Alice B. Gottlieb, MD, PhD

Dermatologists who began to practice medicine when I did may recall the concept of rotational therapy in which patients with psoriasis were switched from one treatment to another primarily due to safety issues. This practice is really something from a bygone era now that we have the biologic therapies. Patients today might be switched from one biologic to another because of primary or secondary treatment failure, but rotational therapy is no longer the paradigm, and I think that biologics have dramatically altered clinical practice in this way.

Although biologic therapies have improved our ability to treat psoriasis effectively, they have also significantly increased health care costs for our patients. Access to these highly effective treatments remains suboptimal, so we need to continue to work toward improving access. In addition, I am optimistic that ongoing clinical research and drug development efforts may empower clinicians to take a more proactive approach to comorbidities such as psoriatic arthritis and cardiovascular disease. Patients with psoriasis who develop psoriatic arthritis do so, on average, approximately 10 years after the psoriasis diagnosis. And, although we can treat psoriatic arthritis when it emerges, we do not yet know whether any of our available therapies can prevent it. We need a regulatory pathway to show such prevention, for both psoriatic arthritis and atherosclerotic cardiovascular disease.

References

Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020;323(19):1945-1960. doi:10.1001/jama.2020.4006

Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058

Lambert JLW, Segaert S, Ghislain PD, et al. Practical recommendations for systemic treatment in psoriasis according to age, pregnancy, metabolic syndrome, mental health, psoriasis subtype and treatment history (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis; part 1). J Eur Acad Dermatol Venereol. 2020;34(8):1654-1665. doi:10.1111/jdv.16684

Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072. doi:10.1016/j.jaad.2018.11.057

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