MADRID, Spain — A novel interleukin-17 inhibitor known as brodalumab (Amgen) achieves significant responses in the signs and symptoms of psoriatic arthritis, results of a randomized phase 2 trial have shown.
Brodalumab will now progress to phase 3 development.
Similar trials of brodalumab in psoriasis show skin responses of 75% on the Psoriasis Area and Skin Index (PASI 75). An even higher bar — PASI 100 — was achieved by 39% to 63% of patients.
This rate is quite high compared with responses to most other drugs in this setting," said lead investigator Philip Mease, MD, from the Swedish Medical Center and University of Washington in Seattle.
Dr. Mease, who presented data here at the European League Against Rheumatism Congress 2013, said the findings from these and previous studies suggest the effects on the skin appear very early in the course of treatment and the effects on the joints appear later.
"These promising data are important," he emphasized. "It is exciting to see proven efficacy in a drug in development. The results suggest that cytokine-targeting strategies aimed at blocking signals through the interleukin-17 receptor may represent an important new treatment strategy."
Interleukin-17 is implicated in the pathogenesis of psoriasis and psoriatic arthritis.
Unlike in rheumatoid arthritis, where there are multiple drugs with non-tumor necrosis factor (TNF) mechanisms of action, "in psoriatic arthritis, we lack alternatives for patients who have safety issues with TNF inhibitors," Dr. Mease explained.
The investigators randomized 113 patients to receive placebo, brodalumab 140 mg, or brodalumab 280 mg. They continued double-blind treatment for 12 weeks, and then all patients went on open-label treatment with brodalumab 280 mg.
At baseline, disease duration was about 8 to 9 years and 50% of patients had previously taken a TNF inhibitor, which could have compromised their response to brodalumab, Dr. Mease pointed out. The median number of swollen joints was approximately 13, and the median number of tender joints was about 24.
"Responses were virtually the same in biologic-naïve patients and those who were previously treated with a biologic, which is reassuring about the drug's efficacy," Dr. Mease said.
Table. American College of Rheumatology Response of 20% With Brodalumab
|Week||Placebo, % (n = 55)||140 mg, % (n = 57)||280 mg, % (n = 56)|
ACR50 and ACR70 were reached in smaller percentages of patients, Dr. Mease reported. "We have to take these results with a grain of salt because patients were not blinded to the drug they were on. However, the results suggest that the effect on the joints gets better over time."
They saw improvement for all components of the ACR (swollen joints, tender joints), C-reactive protein level, disease activity score in 28 joints, and dactylitis and entithesis. They also saw improvement in psoriasis plaques, as had been previously demonstrated.
The safety data are reassuring. There were few serious adverse events — 2 patients with cellulitis (1 in the placebo group and 1 in the 280 mg group) and 1 patient with abdominal pain (in the 140 mg group).
No new safety signals emerged to separate brodalumab from placebo, Dr. Mease reported. There were no opportunistic infections or deaths during the trial.
"The effect of brodalumab on psoriasis is striking, and it may be that it takes more time to show an effect on the joints," said Christopher Buckley, MD, from the University of Birmingham in the United Kingdom. "These data are important, but I think we may find that interleukin-23 blockade will be even more effective than interleukin-17 at the joints," he noted. "Interleukin-17 and 23 are interesting relatives."
Dr. Mease reports receiving funding from Amgen, AbbVie, Biogen Idec, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB. Dr. Buckley has disclosed no relevant financial relationships.
European League Against Rheumatism (EULAR) Congress 2013. Abstract OP0103. Presented June 13, 2013.
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Cite this: Brodalumab Making Progress in Psoriatic Arthritis - Medscape - Jun 21, 2013.