A monoclonal antibody targeting the interleukin-17 receptor A (IL17RA) showed efficacy for the musculoskeletal components of psoriatic arthritis in a multicenter phase II study, investigators reported.

Among patients who received subcutaneous brodalumab in doses of 140 mg every 2 weeks, a 20% improvement according to the criteria of the American College of Rheumatology (ACR20) was achieved by 37% after 3 months of treatment (P=0.03), and 39% of those given 280 mg (P=0.02) compared with 18% of those receiving placebo, according to Philip J. Mease, MD, of the University of Washington in Seattle, and colleagues.

And on the Disease Activity Score in 28 joints (DAS28), both treatment groups had least-squares mean changes from baseline of -0.7 compared with placebo (P=0.002), the researchers reported in the June 12 New England Journal of Medicine.

Interleukin-17 has been implicated in the pathogenesis of psoriatic arthritis, and several agents targeting related signaling pathways are being developed.

In an earlier phase II trial evaluating brodalumab for moderate-to-severe psoriasis, more than 75% of patients experienced significant improvements on skin scores by week 12.

To further investigate the efficacy and safety of this agent for psoriatic arthritis, which affects almost one-third of patients with psoriasis, Mease and colleagues enrolled 168 patients from 29 North American sites.

The trial included a 3-month, double-blind randomized phase with the two different doses of brodalumab, followed by an open-label phase intended to last up to 5 years in which all participants receive the 280 mg dose every 2 weeks.

Patients’ mean age was 53, the majority were women, and almost all were white.

Body mass index averaged 33 kg/m², and mean disease duration was 9 years.

All patients had at least three tender and three swollen joints and were on stable doses of background medications such as methotrexate and steroids. Half had previously received other biologic therapies.

On the Clinical Disease Activity Index, least squares mean change from baseline was -10.6 in the 140 mg group at 12 weeks, and -11.3 in the 280 mg group, compared with -4 in the placebo group (P<0.001).

And on the Psoriasis Symptom Inventory, the change in score was -8.5 in the 140-mg group and -10.9 in the 280-mg group, compared with -1.3 in the placebo group (P<0.001).

Response rates continued to rise after the initial 12-week period, with ACR20 responses seen in 51% and 64% of the original 140 mg and 280 mg groups at 6 months, and in 44% of those originally assigned to placebo.

“Although data from open-label trials need to be interpreted with caution, continued improvements beyond the primary endpoint suggest that a full clinical response among patients with psoriatic arthritis requires longer than 12 weeks, a hypothesis that must be evaluated in longer-term controlled studies,” Mease and colleagues wrote.

Adverse events were reported by 62% and 71% of the lower-dose and higher-dose brodalumab groups and by 65% of patients receiving placebo. The most common were upper respiratory tract infection, fatigue, headache, and diarrhea.

Serious adverse events during the double-blind phase included one case of abdominal pain in a patient receiving 140 mg, one case each of cholecystitis and cellulitis in the 280 mg group, and one case of cellulitis in the placebo group.

In the first year of the open-label phase, the most common adverse events included upper respiratory tract infection, disease flare, and arthralgias.

There were no serious cases of neutropenia, “an important safety outcome, since interleukin-17 is involved in neutrophil homeostasis,” the authors noted. There also were no opportunistic infections and no deaths.

The investigators concluded that “IL17RA is a potential target for the treatment of psoriatic arthritis.”

Limitations of the study included the short treatment duration and relatively small number of patients, so larger studies will be needed to more fully evaluate safety.