Abatacept Approved for Psoriatic Arthritis in Adults; Sirukumab Approval Stalls

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Abatacept Approved for Adult PsA

On June 30, the U.S. Food and Drug Administration (FDA) approved abatacept (Orencia) to treat adults with active psoriatic arthritis (PsA).¹ Abatacept is available as both an intravenous formulation and a subcutaneous injection.² The approval was based on results of two randomized, double-blind, placebo-controlled trials, PsA-I and PsA-II, during which abatacept reduced or improved disease activity in both tumor necrosis factor inhibitor (TNFi)-naive and TNFi-exposed patients with high disease activity, and high tender and swollen joints counts.

During the studies, patients (N=594) had a disease duration of seven years or more. They also had active psoriatic arthritis, with three or more swollen or tender joints despite prior treatment with disease-modifying anti-rheumatic drug (DMARD) therapy, and had one qualifying psoriatic skin lesion of at least 2 cm in diameter. The primary endpoint of the studies was the proportion of patients who achieved ACR20 response at Week 24. In PsA-I and PsA-II, 37% and 61% of patients, respectively, had previously been treated with TNFi.

In PsA-I, which was a dosing study, patients (N=170) were randomized to receive placebo or abatacept intravenously at 3 mg/kg or 10 mg/kg based on weight, or two doses of 30 mg/kg followed by weight-based dosing of 10 mg/kg without escape for 24 weeks. Patients were dosed on Days 1, 15 and 29 and every 28 days thereafter. After Week 24, patients received open-label abatacept every 28 days. Stable doses of concomitant methotrexate, low-dose corticosteroids (equivalent to ≤10 mg of prednisone) and/or NSAIDs were also allowed. When enrolled, approximately 60% of these patients were receiving methotrexate. The ACR20 response for abatacept 10 mg/kg IV at Week 24 was 47.5% vs. placebo at 19% (P<0.05). Prior TNFi or non-biologic DMARD treatment did not dictate response.

In PsA-II, patients (N=424) were randomized (1:1) to receive weekly doses of placebo or 125 mg abatacept subcutaneously without a loading dose for 24 weeks. The treatment was followed by 125 mg subcutaneous abatacept given weekly in an open-label study design. Stable doses of concomitant methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, low-dose corticosteroids and/or NSAIDs were allowed. At randomization, 60.4% of patients were receiving methotrexate. The ACR20 response for 125 mg subcutaneous abatacept at Week 24 was 39.4% vs. placebo at 22.3% (P<0.05). Prior TNFi or non-biologic DMARD treatment did not dictate response.

Both intravenous and subcutaneous abatacept-treated patients had improvements in enthesitis and dactylitis at Week 24. Also at Week 24, more intravenous abatacept-treated patients had a greater decrease from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score compared with placebo-treated patients. Subcutaneous abatacept-treated patients had improvements in the HAQ-DI, but the change was not as pronounced.