New mechanisms, nanobody ‘revolution’ promising for psoriatic arthritis treatment
Click Here to Manage Email Alerts
SCOTTSDALE, Ariz. — Interleukin-17 targeting, a tyrosine kinase 2 inhibitor and the “nanobody revolution” represent a promising new frontier for psoriatic arthritis, according to a speaker here.
Rheumatology is “now entering an era where we’re getting new and different IL-17 inhibitors,” such as bimekizumab (Bimelx, UCB), a dual IL-17A and IL-17F inhibitor approved for psoriasis, Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center/Providence St. Joseph Health, and a clinical professor at the University of Washington School of Medicine, in Seattle, told attendees at the Basic and Clinical Immunology for the Busy Clinician symposium.
He added that the drug “will soon be approved, we hope” for PsA, noting a phase 3 trial from last year finding that more than 44% of patients with PsA achieved minimal disease activity after treatment.
Mease additionally described a “so-called nanobody revolution,” in which studies have suggested molecules of very small size could enable better penetration into hard-to-reach tissue, or less vascularized tissue than larger immunoglobulins. The novel nanobody izokibep (Acelyrin, Inc.) is now in a phase 3 PsA trial and “showed strong results in two different doses” in a phase 2 trial, he said.
“The data that got people sort of intrigued and excited about this whole issue of tissue penetration was this differentiation at week 16 between the 40 and 80 milligram doses, where there was high dose response,” Mease said. “This is something that we’ll have to see, once we see the phase 3 data, whether this was just luck of the draw in the phase 2 trial.”
Mease also highlighted a drug that works via “a new mechanism to us” — deucravacitinib (Sotyktu, Bristol Myers Squibb), a selective, allosteric tyrosine kinase 2 inhibitor. The drug was approved by the FDA in September 2022 for treatment of moderate-to-severe plaque psoriasis and has also shown benefit in active PsA in a phase 2 trial led by Mease.
“The drug works well as a single application today in psoriasis ... and without the FDA black box warning label about safety that the other JAK inhibitors have,” he said. “We anticipate that this will be approved in psoriatic arthritis, and even possibly lupus, in the future.”
However, there remains an issue faced by providers “on an almost daily basis,” Mease said. That is, what to do with a patient who has “tried everything.” To this end, there have been “promising” results on the use of dual biologics, according to Mease.
Results from a Spanish study that assessed a variety of dual treatment options, such as ustekinumab (Stelara, Janssen) and a TNF inhibitor, in patients with inflammatory bowel disease and PsA or axial spondyloarthritis, showed that two-thirds of participants saw remission or low disease activity.
Outside of rheumatology, another study in ulcerative colitis found synergy between the TNF inhibitor golimumab (Simponi, Janssen) and guselkumab (Tremfya, Janssen), an IL-23 inhibitor.
After treatment with either golimumab or guselkumab alone, researchers found “a downward movement of the ‘bad guy’ genes and an upward movement of the ‘good guy’ genes,” Mease said. However, when combined, “we’re seeing much more change in the gene expression, more than you would expect if you were just adding golimumab and guselkumab together.”
Said Mease: “It raises the question: If we start to put together some of our treatments — JAK inhibitor with a TNF inhibitor, IL-17 with an IL-23 inhibitor, and so on and so forth — are we getting to a more exciting and more disease-altering state by using this combination?”
Collapse
Mease PJ. PsA Immunology Basics Bench to Bedside. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 17-18, 2024; Scottsdale, Arizona (hybrid meeting).
Read more about
Click Here to Manage Email Alerts