A new treatment strategy with a novel IL-17 receptor inhibitor
By Phoebe Starr
Madrid, Spain—Data from a phase 2 trial for a novel interleukin (IL)-17 inhibitor, called brodalumab, suggest that it may become a new option for the treatment of psoriatic arthritis. Brodalumab was effective in reducing the signs and symptoms of psoriatic arthritis at week 12, and responses were further improved at week 24.
Previous studies have shown that brodalumab achieves rapid improvement in the skin, reducing psoriatic plaques markedly. Based on these promising data, brodalumab will enter phase 3 testing.
“Unlike TNF [tumor necrosis factor] inhibitors, brodalumab works more rapidly at the skin than at the joints, while the TNF inhibitors show an effect on the joints earlier than on the skin in PsA [psoriatic arthritis],” said lead investigator Philip J. Mease, MD, of Seattle Rheumatology Associates, and Swedish Medical Center, Seattle, WA, at the 2013 European League Against Rheumatism (EULAR) annual meeting.
Dr Mease told listeners that brodalumab represents one of the first agents with a different mechanism of action than TNF inhibition to show an effect on psoriatic arthritis, providing another treatment option for patients who have had a poor response to TNF inhibitors or who are intolerant to those agents.
Brodalumab is an inhibitor of the IL-17 receptor. IL-17 is implicated in the pathogenesis of psoriasis and psoriatic arthritis.
“The results suggest that cytokine-targeting strategies aimed at blocking signals through the IL-17 receptor may represent an important new treatment strategy,” he stated.
A previous study of brodalumab in patients with psoriasis and >3% skin involvement was conducted by Dr Mease and colleagues. In that study, responses of 75% on the Psoriasis Area and Severity Index (PASI 75) were observed in 77% to 83% of patients, and 100% improvement (PASI 100) was achieved in 39% to 63% of patients.
The study that Dr Mease presented at EULAR 2013 randomized 113 patients with psoriatic arthritis to brodalumab 280 mg (N = 56) or to brodalumab 140 mg (N = 57) and 55 patients to placebo for 12 weeks of double-blind treatment. After that, all patients received open-label brodalumab 280 mg.
At baseline, disease duration was approximately 8 to 9 years, 50% of patients had been previously exposed to a TNF inhibitor, the median number of swollen joints was approximately 13, and the median number of tender joints was approximately 24.
At 12 weeks, a response of at least 20% on the American College of Rheumatology 20% criteria for improvement (ACR20) was reached in 18.2% of patients receiving placebo, 36.8% of patients receiving brodalumab 140 mg, and in 39.3% of patients receiving the 280-mg dose. There was no difference in response in biologic-naïve or biologic-exposed patients.
Psoriatic arthritis responses were improved over time. At week 24, the ACR20 response was 43.5% with placebo, 51.5% with brodalumab 140 mg, and 64.4% with brodalumab 280 mg. ACR50 and ACR70 were reached in smaller percentages of patients.
Brodalumab improved all components of the ACR measures (ie, swollen joints and tender joints), C-reactive protein level, 28-joint disease activity score, and dactylitis and enthesitis, as well as skin involvement.
Dr Mease noted that the safety data were reassuring, with few serious adverse events. No new safety signals emerged for brodalumab, and there were no opportunistic infections or deaths during the trial.