New classes of psoriatic arthritis drugs in clinical trials show promise
By Kathleen Hoffman, PhD, MSPH
Psoriatic Arthritis (PsA) is an inflammatory autoimmune disease affecting approximately one to two percent of the population. While psoriasis causes red and scaly patches on the skin, PsA creates mild to severe pain and swelling of any joint. About 5 to 30 percent of patients with psoriasis eventually develop PsA, and 85 percent of people with PsA have psoriasis as a comorbidity. Because there is no cure, treatment is focused on symptom management.1,2,3
That is the high-level view. At the experiential level, swollen and inflamed joints impact the quality of life for PsA patients. There are over 16,000 posts on Inspire discussing PsA.
…I have changed my diet to gluten free, dairy free and Paleo and have lost the weight gain from the [steroid]. I really want to get off the [steroid] totally, but just have too much pain without it.
Psoriatic arthritis is a pain….in many places. I too have had it for too many years to count!
Recently, there is encouraging news from several clinical trials. The novel treatments for PsA include monoclonal antibodies and TK2 inhibitors that put the brakes on the cytokines that are active in the inflammatory process.
Bimekizumab is the first dual inhibitor for the treatment of PsA, targeting both IL17A and IL17F. Other approved monoclonal antibodies, such as secukinumab or ixekizumab, act on IL17A alone. Research shows that IL17F, while structurally similar to IL17A, supports IL17A’s role in pathogenic inflammation. Targeting both cytokines was hoped to be more effective.4
An open label extension phase 2b study called BE ACTIVE 2 (NCT03347110) evaluated the safety and long-term effectiveness of bimekizumab in patients with PsA. The American College of Rheumatology (ACR) uses a scale: ACR20, ACR50, or ACR70 referring to a 20, 50, or 70 percent improvement in joint pain and swelling, among other criteria to report findings. At 12 weeks, 208 participants achieved ACR 20/50/70 responses 76 (62 percent) 46 (37 percent) and 27 (22 percent) respectively. At week 108, those results remained unchanged in 80/78/81
percent of the patients. Only 9.3 percent experienced adverse effects, but no deaths or serious cardiac events occurred. The results suggest excellent response rates paired with a strong safety profile.5
Other drugs in trials include:
Deucravacitinib is a new TK2 inhibitor for PsA. In Phase 2 trials 137 of 180 patients taking the drug for 16 weeks showed more ACR 20 responses when compared to the placebo (52.9% and 62.7% versus 31.8%). It also showed a good safety profile, with only mild to moderate adverse events, such as cold symptoms and headache. A phase 3 trial (NCT04908189) is being conducted now.,
Updacitinib is a JAK inhibitor that is already approved for treating rheumatoid arthritis (RA). Phase 3 trials (NCT04908189) tested the drug versus placebo in patients with active PsA who had taken biologics (bDMARDs) but either didn’t respond adequately or who could not tolerate them. Patients received doses of either 30 or 60 mg. At week 12, a greater proportion of patients receiving upadacitinib achieved ACR20: 56.9% and 63.8% vs the 24.1% taking the placebo. Scores also improved on the S36 Quality of Life health questionnaire.
Netakimab is a monoclonal antibody that acts as an IL-17 Inhibitor. A phase 3 study called PETERA (NCT03598751) included 5 different surveys of the Quality of Life for patients with moderate to severe PsA at 24 weeks of treatment. The authors concluded that taking netakimab “demonstrated rapid improvement in QoL, work productivity and physical function in [patients] with PsA.”
Inspire members are looking to both treatments and lifestyle changes to improve their lives while having PsA:
I also felt that I was going to be a complete failure with the biologics after failing on the first 4 I tried…but the ones that had a “little” effect [offered me] a chance to figure out how to do better… A brief list of what helped was a pain med, bumping the [drug] dosing to one injection every 10 days, physical therapy once a week every week, yoga, eliminating peppers, potatoes and MSG from my diet, also being sure to correct any vitamin deficiencies of which I had a few…I am now on [drug]. It has been about a year and is working well for PSA and psoriasis. After initial startup I only inject every 8 weeks so this is also a good thing.
It’s a lot of work for people with PsA just to feel good and stay that way. Clinical trials and new treatments are increasingly pinpointing the biochemical targets that cause PsA flareups. These research findings are showing that new treatments can help more patients achieve long-term, durable remission.
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