Interleukin Inhibitors for Moderate to Severe Psoriasis

April Armstrong, MD, MPH, presented the session “The Role of Interleukin Inhibitors in the Treatment of Moderate to Severe Psoriasis” during the 2nd day of the Interdisciplinary Autoimmune Summit.

Dr Armstrong started by stating that psoriasis is “one of the most common immune-mediated conditions in the US,” affecting more than 7.5 million adults. She mentioned that psoriatic nail disease “effects about 50% to 80% of patients with psoriasis” and it can be a “herald sign for psoriatic arthritis.” In addition to psoriatic arthritis, comorbidities include cardiovascular and cardiometabolic diseases, psychiatric disorders, malignancies, and other immune-mediated diseases.

She then discussed the psoriasis inflammatory pathway and where biologics act. “The first major player in terms of psoriasis pathogenesis is the activation of myeloid dendritic cells,” Dr Armstrong remarked. She pointed out that Th17 cells are the “predominant cell type and the predominant pathway that is involved in psoriasis pathogenesis.” Th17 cells secrete IL-17, IL-22, and TNFα.

Dr Armstrong moved on to a discussion of the biologics available to treat plaque psoriasis. The first class is anti-TNα therapies, which “can work ‘upstream’ as well as ‘downstream.’” The FDA-approved TNF inhibitors are etanercept, adalimumab, infliximab, and certolizumab.

Next are the FDA approved IL-17 inhibitors: secukinumab, ixekizumab, brodalumab. Secukinumab and ixekizumab have “identical mechanism of action, binding to IL-17A, and they treat both psoriasis as well as psoriatic arthritis,” stated Dr Armstrong. She indicated that brodalumab has a different mechanism of action, binding to IL-17 receptor alpha and inhibiting the actions of IL-17 A, IL-17 F, IL-17 C, and IL-17E.

 The IL-23 inhibitors ustekinumab, guselkumab, and risankizumab are FDA-approved for psoriasis and psoriatic arthritis; tildrakizumab is only approved for psoriasis currently.

Dr Armstrong delved into why determining whether the patient has psoriatic arthritis is the first step when deciding on the appropriate psoriasis therapy. “The reason for this is because if the patient has psoriatic arthritis, then we really want to go directly down to the choices of the systemic therapies that can address both psoriatic arthritis and psoriasis,” she said.

Next, Dr Armstrong described how to choose a biologic as a “3-legged stool of efficacy, safety, and convenience, and along with that also access.” She shared data on the estimated number of patients needed to treat relative to placebo to achieve PASI 75 by month 3 or 4 and summarized, “Essentially, nearly every patient who comes through the door if we treat [them] with some of our top biologics, we’re going to get them clear. The biologics that seem to rank among the top are our IL-17 and IL-23 inhibitors.”

In adults, TNF inhibitors can be used for psoriatic arthritis. They should be avoided in those with demyelinating disease or hepatitis B, and they aren’t preferred for those with a history of latent tuberculosis or advanced congestive heart failure. For patients who are pregnant, certolizumab is the TNF of choice. IL-17 inhibitors can be used for psoriasis and psoriatic arthritis but should be avoided in patients with a history of inflammatory bowel disease. IL-23 inhibitors can also be used for both psoriasis and psoriatic arthritis with fewer injections; they need more evidence for psoriatic arthritis involving the spine.

Laboratory monitoring requirements needed at baseline before starting a patient on a biologic include tuberculosis, complete blood cell count, and hepatitis B and C, with yearly tuberculosis testing in high-risk patients and those on TNF inhibitors.

After taking attendees through a detailed review of the available IL-17 and IL-23 inhibitors, Dr Armstrong brought up the emerging IL-17A and F inhibitor bimekizumab, which will be coming soon. “Over 90% of patients achieve PASI 90 by week 16, with early rapid onset of response. [Patients] will definitely see a difference as early as 2 weeks and certainly by 4 weeks,” she stated.

Lastly, Dr Armstrong discussed switching and dose calculations. She recommended waiting at least 6 months to switch for patients who have never responded optimally to a biologic (primary failure) and then consider switching to another class of biologics. For patients who responded initially but then lost response over time (secondary failure), options include dose escalation to shorten the interval between injections, a within class switch, or across class switching.

Reference

Armstrong AW. The role of interleukin inhibitors in the treatment of moderate to severe psoriasis. Presented at: Interdisciplinary Autoimmune Summit; April 21–24, 2022