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VBCR - August 2016, Vol 5, No 4 - Psoriatic Arthritis
Walter Alexander

London, United Kingdom—An early-phase study of bimekizumab, a monoclonal antibody potently and selectively inhibiting interleukin (IL)-17A and IL-17F, demonstrated strong responses in skin and joints of patients with psoriatic arthritis. IL-17A and IL-17F, key proinflammatory cytokines, are overexpressed in psoriatic skin lesions, said Sophie Glatt, MD, UCB Celltech, Slough, United Kingdom, in an oral presentation at the 2016 European League Against Rheumatism Annual Congress.

The 52 patients with psoriatic arthritis in the study conducted by Dr Glatt and colleagues had a mean disease duration of 6.6 years. They were randomized to 1 of 4 doses of bimekiz­umab (n = 38) or placebo (n = 14). Those in the bimekizumab arm received a single loading dose (80-560 mg) administered at week 0; additional doses (40-320 mg) were administered at weeks 3 and 6. Efficacy end points included American College of Rheumatology (ACR)20, ACR50, and mean Disease Activity Score C-reactive protein (CRP) scores for joints, and Psoriasis Area and Severity Index (PASI) scores for skin.

The mean CRP at baseline was 12.5 mg/mL, and patients with skin involvement of >3% had a mean PASI score of 15.9. Dr Glatt and colleagues observed that the onset of response was rapid for skin and for joints. For the top 3 bimekizumab doses, the ACR20 response rate was 80% (n = 30) at week 8 compared with 17% in the place­bo group (n = 12). In an interview, Dr Glatt commented that typical ACR20 rates for anti−tumor necrosis factor (TNF) or anti−IL-17A agents at weeks 12 and 8 are approximately 60% and 50%, respectively. A Bayesian analysis showed a high posterior probability that the observed bimekizumab ACR20 response rate at week 8 is greater than that of placebo, and of that reported for anti-TNF and anti−IL-17A agents.

Dr Glatt characterized the ACR50 rate of 67% at week 8 with bimekizu­mab as “very high,” noting that it compared favorably to the generally found ACR50 rates of 40%.

Clinically relevant reductions in disease activity measures occurred early and were maintained to week 20. Increased ACR70 response rates were observed within 2 weeks of the first bimekizumab infusion, and maximal ACR response was achieved at week 16 (ACR70, 37%). Mean PASI 75 and PASI 100 response rates were 0% for placebo (n = 5), and 100% and 87% for bimekizumab (n = 15), respectively, at week 8. “That is really high,” Dr Glatt observed.

Two cases of fungal infection (oropharyngitis and vulvovaginal candidiasis) were classified as mild. The majority of treatment-emergent adverse events were mild or moderate, with no severe adverse events attributed to treatment.

“This phase 1b proof of concept trial in patients with psoriatic arthritis, bimekizumab…showed no new or unexpected safety signals in this data set,” Dr Glatt concluded.

She also reported that bimekizu­mab’s fast onset of clinical effects was observed in the skin and joints, with maximal response as early as week 8, and duration of response maintained up to week 20.

“The ACR rate findings are very good, particularly for those patients with skin involvement. Also, Bayesian analysis indicated that the bimekizu­mab ACR20 response rate is greater than that reported for current therapies, including anti−IL-17A,” Dr Glatt explained. “So our results support the idea that inhibition of both IL-17A and IL-17F could provide additional clinical benefit in IL-17−mediated diseases.”

“Of course we need to see similar results in the larger phase 2 and 3 studies,” she added

A major clinical development program for this molecule with large phase 2 and 3 trials is likely, Dr Glatt stated, including investigations for other indications. An early-phase trial (first in man) of bimekizumab in mild psoriasis has had similarly positive results.

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Last modified: September 27, 2016
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