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.

The safety profiles of these trials were comparable to rheumatoid arthritis (RA) safety trials. The most serious adverse events in adult RA studies were serious infections and malignancies. In the PsA-II trial, the most common adverse events were bronchitis, nasopharyngitis and upper respiratory tract infections.

The Arthritis Advisory Committee of the FDA voted against recommending approval of sirukumab for the treatment of moderate to severe active RA in adults, … [citing] safety concerns.

Sirukumab Approval Stalls

On Aug. 2, the Arthritis Advisory Committee of the FDA voted against recommending approval of sirukumab for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults who have had an inadequate response to or are intolerant to one or more DMARDs.³ The committee cited safety concerns and voted 12–1 that the benefits of the treatment do not outweigh its risks.⁴

According to the innovator company, Johnson & Johnson, sirukumab is an anti-interleukin (IL)-6 monoclonal antibody, but it blocks the IL-6 pathway differently from other IL-6 inhibitors that are currently FDA approved for treating RA.

At the advisory committee meeting, the efficacy and safety data of sirukumab were reviewed. These data came from five Phase 3 clinical trials with more than 3,000 patients with RA, who include patients with active disease despite previous DMARD and biologic treatment. Doses used in the trials included 50 mg sirukumab every four weeks and 100 mg sirukumab every two weeks. The agent showed significant efficacy in improving the signs and symptoms of RA, inhibiting structural damage progression and showing improvements in measured patient-reported outcomes, such as fatigue, pain, physical function and quality of life.

During the trials, common adverse events included laboratory abnormalities, colds, upper respiratory tract infections and injection site redness, pain or swelling. Serious adverse events included infections, such as abscess, cellulitis, gastrointestinal perforations, hypersensitivity reactions, lipid level elevations, osteomyelitis, pneumonia, thrombocytopenia and sepsis. Cardiovascular adverse events, malignancies and deaths were also observed.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. U.S. Food and Drug Administration. Letter: Bristol Myers Squibb supplemental approval letter. 2017 Jun 30.
2. Bristol-Myers Squibb Co. News release: Bristol-Myers Squibb’s Orencia (abatacept) receives FDA approval for treatment of active psoriatic arthritis (PsA) in adults. 2017 Jul 6.
3. Johnson & Johnson Services Inc. News release: FDA advisory committee does not recommend approval of sirukumab for the treatment of moderately to severely active rheumatoid arthritis. 2017 Aug 2.
4. Barber J. FDA advisory panel votes against approval of Johnson & Johnson’s experimental RA drug, Plivensia. FirstWord Phrama. 2017 Aug 2.