Treat-To-Target Is Popular, But Not Without Its Critics

We had the pleasure of attending the 2019 American Academy of Dermatology (AAD) annual conference, which showcased ground-breaking developments in dermatologic therapy. Biologics remained a focal point of discussion as new additions that further bolster the already strong treatment armamentarium in psoriasis were presented. Given the near gold-standard status of therapeutic options for this disease and an apparent continued improvement in safety, the enthusiasm for biologic success has led to a number of unique questions pertaining to their use. Of particular interest was the appropriate aggressiveness and realistic expectations of treatment. As was evidenced by several presentations at the AAD, skepticism continues to exist regarding the everyday applicability of recently published guidelines declaring <1 percent body surface area (BSA) as an ideal goal.

Treat-to-target is a hot topic in the medical field today. Successful implementation of target algorithms aiming to prevent irreversible sequelae in diseases including diabetes mellitus, rheumatoid arthritis, and hypercholesterolemia has clearly intrigued dermatologists. It is very clear from previous work that the reduction in Psoriasis Area Severity Index by 75 percent (PASI 75) confers a significantly meaningful benefit for patients and that statistically higher PASI improvements correspond to improved quality of life. Additionally, the evidence that psoriasis carries a host of detrimental cardio-metabolic effects that might also be affected by successful treatment could support more aggressive approaches. But the relative value of the incremental benefit between PASI 75 and clearance is still unclear. Accordingly, while the treat-to-target concept has become increasingly popular in psoriasis, this campaign is not without its critics.

Dr. Kenneth Gordon of the Medical College of Wisconsin gave a thoughtful presentation regarding the role of treat-to-target in psoriasis. His central theme highlighted the disparity between treat-to-target’s applications on a population scale compared to an individual patient level. Biologics targeting IL-17 and IL-12/23 have revolutionized treatment strategies, affording patients rapid improvement with minimal side effects. One need look no further than the heralded effectiveness measure: PASI 75; new biologic effectiveness has rendered it increasingly defunct. Instead, PASI 90 has become the measure of choice in many studies, and PASI 100 has been increasingly referenced as a future goal. The unintended consequence of these advancements is that for the average psoriasis patient, the precise biologic choice matters less. Thus, the natural question becomes: where do we draw the line between effective treatment and overtreatment?

A goal of <3 percent BSA or PASI 75 at three months and <1 percent BSA from six months onward are included in the consensus statement for target BSA in psoriasis from the National Psoriasis Foundation. Dr. Gordon posited that this target is pragmatic on a population level, but falters on a patient to patient basis. He explained that patients with limited BSA involvement content with their current regimen may gain little from the proposed guideline. Moreover, limited high-quality evidence exists to suggest that irreversible sequelae are associated with low, though not totally clear BSA. Results from the Incident Health Outcomes and Psoriasis Events (iHOPE) cohort failed to illustrate an increase in all-cause mortality among patients with low disease activity (BSA <10 percent) compared to controls. It remains unclear whether aggressive treatment beyond a threshold of BSA affects other aspects of health.

Further undermining the treat-to-target premise were discussions by Dr. Joel Gelfand from University of Pennsylvania and Dr. Nehal Mehta, a cardiologist from the National Institutes of Health. Dr. Gelfand presented a study of secukinumab’s effect on aortic wall inflammation compared to placebo utilizing 18-fludeoxyglucose positron emission tomography-computed tomography. While patients saw significantly greater skin improvement on secukinumab compared to placebo at 12 weeks, imaging failed to demonstrate a statistically significant change in vascular inflammation between secukinumab and placebo. While week 52 results are still pending, this suggests that despite excellent cutaneous response to secukinumab, the underlying vascular inflammation still remains. Additionally, Dr. Mehta’s presentation focused on the cardiac risks of psoriasis, emphasizing that in observational studies, there is a clear correlation between decreased PASI and decreased cardiovascular risk. However, randomized clinical trials have failed to demonstrate such improvement. For example, in a trial comparing vascular inflammatory response to adalimumab, phototherapy, and placebo in psoriasis patients, adalimumab and phototherapy had neutral effects compared to placebo in reducing vascular inflammation. Ultimately, we do not yet know whether there is a difference between the severe patient under good control and the mild patient under poor control.

Thus, we wait for more data regarding the benefit from treat-to-target in psoriasis and the evidence to compellingly support the concept that all patients should have a BSA of less than one percent after six months of treatment. Future studies may elucidate universally appropriate targets for treatment but clearly the responsibility today remains with the individual physician and patient to collectively decide whether or not these are the goals they should try to achieve.

Kevin T. Savage, BA is a rising fourth year medical student at Drexel University College of Medicine. He is currently completing a predoctoral research fellowship with Dr. Alexa B. Kimball in the Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS) in the Department of Dermatology at Beth Israel Deaconess Medical Center.

Alexa B. Kimball, MD, MPH is the President and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center and Professor of Dermatology at Harvard Medical School in Boston, MA. She is a Consultant and Investigator for Novartis, Abbvie, UCB, Lilly, Janssen, BMS and Pfizer. Her fellowship program receives funding from Janssen, Abbvie and the National Psoriasis Foundation.

Illustration by April Brust

More from Op-Med