IL-17 inhibitors may break TNFi ‘glass ceiling’ in psoriatic arthritis prescribing
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Although TNF inhibitors remain the first choice biologic for many rheumatologists treating psoriatic arthritis, interleukin-17 inhibitors may soon overtake them, according to a market analysis from Spherix Global Insights.
Topline results from the analysis showed that a plurality of rheumatologists — 18.7% — reported that efficacy in joint involvement was the most important factor in making treatment choices, followed by efficacy in skin involvement (12%) and long-term safety (11.5%). When asked to rate various drugs based on these attributes, rheumatologists gave the highest marks to Humira (adalimumab, AbbVie), a TNF inhibitor, and the IL-17 inhibitors Cosentyx (secukinumab, Novartis) and Taltz (ixekizumab, Eli Lilly).
!["[TNF inhibitors] have set a glass ceiling that other biologics have not been able to break through," Atul Deodhar, MD, said.](/~/media/slack-news/rheumatology/misc/infographics/2024/rh0324deodhar_graphic_01.jpg?w=800)
“I did not take this survey, but if these are rheumatologists, the top priority is the joints,” Atul Deodhar, MD, of the Oregon Health and Sciences University School of Medicine, told Healio.
On this point, it has been Deodhar’s experience that rheumatologists and patients are generally in agreement.
“Most patients place an emphasis on the joints rather than the skin,” he said. “They want to be able to move around, go to work and exercise. For most patients seen in rheumatology clinic, skin often takes a back seat to joints. Of course they would like to have 100% clear skin, but they say, ‘If the psoriasis is in my scalp I can wear a hat, and if it is on my shins I can wear pants.’”
The Spherix data underscore these points from the physician perspective. The group recently surveyed more than 100 rheumatologists regarding their prescribing habits in PsA. They queried respondents on individual medications, drug classes and therapeutic targets, among other topics. According to the findings, efficacy in joint involvement, efficacy in skin involvement and long-term safety, in that order, were the attributes regarded as most important for rheumatologists when choosing a drug.
That said, when psoriatic lesions appear on a patient’s face, this can shift the priorities a bit, according to Deodhar, who was not involved in the Spherix analysis.
“If it is in a place where they are unable to hide it, skin becomes more important,” he said.
In addition, genital psoriasis can be “problematic” for many patients, particularly when it comes to intimacy, Deodhar added.
“Also, palmoplantar pustulosis, which occurs on the soles of the feet or the palms, can be very painful and distressing,” he said.
However, because these conditions are less common, Deodhar suggested listening to patients to determine which treatment option is most attractive to them.
“Most of the time, when we are treating patients, they will say my joints are doing well but my skin is not, or vice versa,” he said.
‘Glass ceiling’ of TNF
The Spherix market analysis additionally asked rheumatologists about specific agents targeting the joints. Data showed that Humira and Cosentyx topped the list for each of their respective drug classes. These two medications yielded comparable preference for both joint and skin involvement along with safety parameters.
“TNF inhibitors are the first biologic medications that come to mind when a patient fails methotrexate, leflunomide or other first-line therapies,” Deodhar said. “Rheumatologists are very comfortable with them, given that they have been using them in rheumatoid arthritis, PsA, spondyloarthritis and other conditions. They have set a glass ceiling that other biologics have not been able to break through.”
Part of the reason for that is the consistency.
“Joint-wise, all TNFs are mostly similar,” Deodhar said.
However, the treatment landscape in rheumatology is constantly shifting. A significant shift in recent years came with the advent of IL-17 inhibition.
“IL-17 inhibitors have been shown to be as effective as TNF inhibitors when treating the joints and clearly superior when treating the skin,” Deodhar said.
According Spherix, when asked for their preferred mechanism of action when treating PsA, 71% of rheumatologists in 2022 said TNF inhibitors, while just 15% reported a preference for IL-17 inhibitors.
However, by the end of 2023, a dramatic shift had occurred. In a follow-up survey, just 41% said they prefer TNF inhibitors, while 38% expressed a preference for IL-17 inhibitors.
Further data from the Spherix study showed that 41% of rheumatologists indicate that the approval of the IV formulation of Cosentyx will increase their overall use of the drug in PsA.
Meanwhile, several head-to-head studies between TNF inhibitors and IL-17 inhibitors have been conducted, Deodhar added.
“Etanercept (Enbrel, Amgen) is the second most commonly used TNF inhibitor,” he said. “It is as good as other TNF inhibitors on the joints, but it is not very good on the skin.”
That said, efficacy in the skin is not the only reason to choose IL-17, according to Deodhar.
“An additional benefit of Cosentyx in the United States is that the 150 mg and 300 mg doses cost the same,” he said. “We like to increase the dose of a medication if it is not working, and Cosentyx allows us to do that easily.”
By comparison, even the IL-17 inhibitor Taltz does not offer that feature, according to Deodhar.
Clinicians are encouraged to view the many head-to-head trials between TNF inhibitors and IL-17 inhibitors to determine the most efficacious choice for each of their patients. They may also consider the safety profile of each of those products.
IL-17 generally ‘safer’ than TNF
“My gut feeling is that IL-17 inhibitors are safer when it comes to a number of things,” Deodhar said.
As an example, he noted a reduced incidence of bacterial infections like pneumonia and tuberculosis at the top of the list.
“These complications are less of a problem with IL-17 inhibitors,” he said.
The importance of the IL-17 cytokine in controlling mucosal surfaces and fungi on the skin surface is critical to its ability to minimize infections, according to Deodhar.
If there is a concern, it pertains to skin, oral and vaginal candida infections that can occur in the setting of IL-17 inhibitor use.
“But since this drug class arrived, we have become comfortable with treating these fungal infections,” Deodhar said.
“What is most important is that larger worries like congestive heart failure and malignancy risks are not present for IL-17 inhibitors the way they are with TNF inhibitors,” he added. “Thus, the feeling among rheumatologists is that they are safer.”
References:
Special Topix: Psoriatic Arthritis (US) Q4 2023. https://www.spherixglobalinsights.com/rheumatology/
Published Dec. 15, 2023. Accessed Feb. 14, 2024.
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