Clinicians treating PsA may no longer be 'throwing a dart' to choose optimal drug
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Novel therapies are providing hope for more targeted therapy options in managing the myriad manifestations of psoriatic arthritis, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.
“I tell patients: you are going to be unique,” Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, said in his presentation. “There is not going to be another patient like you.”
Individuals with psoriatic arthritis (PsA) can experience enthesitis, dactylitis, spondylitis, uveitis, invasive bowel disease and other gastrointestinal complications, in addition to the spinal, dermal and musculoskeletal complications that are most common. “We have to wear our internist cap to make sure all these various issues are being assessed and addressed,” Mease said.
The good news is that emerging clinical trials have provided a range of therapeutic options to treat many of the unique, individual patients who Mease discussed.
For example, the subcutaneous human interleukin (IL)-12 and IL-23 antagonist ustekinumab (Stelara, Janssen) has shown strong efficacy in the skin and some efficacy in the joints. Mease noted that ustekinumab has demonstrated superiority over TNF inhibition in patients with enthesitis. “This raises an interesting question: Are there some domains where there might be superiority of one mechanism over another?” he said. “This needs to be further explored.”
In a study comparing the IL-17A antibody ixekizumab (Taltz, Lilly) with adalimumab (Humira, Abbvie), ixekizumab yielded simultaneous achievement of complete clearance of the skin and a “high threshold” of efficacy in the joints, according to Mease. “Ixekizumab was also superior in enthesitis and dactylitis,” he said.
To that point, the EXCEED trial compared a 300 mg dose of secukinumab (Cosentyx, Novartis) with the standard 40 mg dose of adalimumab in patients with no methotrexate background therapy. Secukinumab was slightly better in terms of joint parameters but “clearly superior” for the skin, according to Mease.
“To summarize these two head-to-head trials, they are showing us that IL-17 can do as well as TNF inhibitors in musculoskeletal domains and a little better than TNF inhibitors in skin domains,” Mease said, noting that they were “similar” in terms of safety. “This gives us a better handle when explaining treatment options to patients. IL-17 [therapies] will be good workhorses for us just as TNF inhibitors have been in retaining this disease.”
With that in mind, Mease also discussed the IL-17A/IL-17F inhibitor bimekizumab (UCB). “It works very well as a treatment for psoriatic arthritis,” he said, noting that the drug is currently “working through final stages of phase 3.”
Turning to “newcomers” to PsA therapy, the IL-23 inhibitor guselkumab (Tremfya, Janssen) has shown strong efficacy in terms of ACR response, skin and functional improvements, according to Mease. “It is clearly effective in treating PsA,” he said. “The safety profile is very good. There is no signal for malignancy, IBD or serious infections.”
Also in the IL-23 class is risankizumab (Skyrizi, Abbvie). “Like guselkumab, it has a very long mode of action,” Mease said.
The final IL-23 drug Mease mentioned was tildrakizumab (Ilumya, Sun Pharma). “This is a new class that we are going to be working with more in association with our dermatology colleagues who are already using these drugs in their patients with psoriasis,” Mease said.
Turning to oral medications, Mease highlighted the PDE-4 drug (Otezla, Amgen) and the janus kinase (JAK) inhibitor tofacitinib (Xeljanz, Pfizer). “Several other oral medications are on the way,” he said.
Another JAK inhibitor, filgotinib (Gilead) has shown particularly strong improvements in enthesitis, according to Mease. “This will be proceeding in phase 3,” he said.
Also in the JAK category, upadacitinib (Rinvoq, Abbvie) has yielded high rates of ACR response and strong skin activity, with resolution of enthesitis and dactylitis. “Safety data shows a slightly greater rate of infection and herpes zoster in the 30 mg dose compared with the 15 mg dose,” Mease said.
While these data from several drug classes and multiple parameters of PsA activity are encouraging, Mease stressed that developing biomarkers to see who will benefit from each class of drug is the next important piece of the puzzle. “In terms of unmet needs, we need to try to understand who is going to respond best to a TNF inhibitor, a JAK inhibitor, IL-17, IL-23, rather than throwing a dart and picking a therapy,” he said.
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Mease PJ. Psoriatic Arthritis: 2020 Update. Presented at: Congress of Clinical Rheumatology-West annual symposium; October 8-11, 2020 (virtual meeting).
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