Orencia Fails to Reduce Disease Activity in Patients with Early Active Primary Sjögren’s Syndrome, Trial Shows

Orencia (abatacept), an immunotherapy used in rheumatic diseases, failed to reduce disease activity in patients with early active primary Sjögren’s syndrome after 24 weeks of treatment, results from the ASAPIII Phase 3 trial show.

However, more patients reported an easing of disease symptoms while taking Orencia, compared to a placebo.

The study was followed by a 24-week open-label extension part, whose first results were presented at the 2019 American College of Rheumatology/The Association of Rheumatology Professionals (ACR/ARP) Annual Meeting held recently in Atlanta, Georgia.

Results were shared in the poster, “Efficacy and Safety of Abatacept in Patients with Early Active’ Primary Sjögren’s Syndrome – Open-label Extension Phase of a Randomized Controlled Phase III Trial.”

Orencia is a biological therapy by Bristol-Myers Squibb, approved in the U.S. and Europe for reducing inflammatory symptoms in patients with rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis, and psoriatic arthritis. The medication is available for infusion (into the vein) or injectable (under the skin) administration.

Its active ingredient targets two surface proteins, called CD80 and CD86, which are necessary for the activation of immune cells and inflammatory reactions. By blocking these proteins, Orencia interferes with the communication between immune cells, thereby lessening inflammation.

Orencia is often used after failed treatment with a disease-modifying anti-rheumatic drug (DMARD) such as methotrexate, but it can also be used as first-line therapy.

Most traditional anti-rheumatic therapies used in RA and lupus have been tried in primary Sjögren’s syndrome but with limited results. No biological agent has yet been approved for the treatment of primary Sjögren’s syndrome, which is the most common systemic autoimmune disease after RA.

An earlier open-label study showed that Orencia, given by under-the-skin injections, could reduce disease activity and fatigue while improving quality of life in adults with early and active primary Sjögren’s syndrome. The study also demonstrated Orencia was well-tolerated by these patients.

Based on the promising results, researchers at University Medical Center Groningen, in the Netherlands, in collaboration with Bristol-Myers Squibb, ran a larger, double-blind, placebo-controlled Phase 3 clinical trial — called ASAPIII (NCT02067910) — to evaluate the efficacy and safety of Orencia for adults with primary Sjögren’s syndrome, who had short disease duration and active disease.

ASAPIII included 80 adult patients with a disease duration of seven years or less and moderate to high disease activity. Patients were given either weekly subcutaneous injections of 125 mg Orencia (40 patients) or a placebo (40 patients) for 24 weeks.

DMARDs were previously used by 45% of the Orencia-treated patients, and by 40% of the placebo group.

After the study’s main part, an open-label extension phase followed in which 78 patients from both groups received Orencia for an additional 24 weeks. The total study duration — double-blind plus extension phase — was 48 weeks.

The primary efficacy measure of the trial was not met. No differences were seen in disease activity (as measured by EULAR Sjögren’s syndrome disease activity score or ESSDAI) between patients treated with Orencia and those on the placebo at the end of the study’s main part (24 weeks).

However, a greater number of patients on Orencia reported experiencing a clinically significant reduction in symptoms (as assessed by EULAR Sjögren Syndrome Patient Reported Index or ESSPRI). Orencia also reduced the overactivity of B-cells, the immune cells involved in Sjögren’s syndrome.

At the ACR/ARP 2019 meeting, researchers presented the first results of the extension phase (week 24 to 48), focusing on symptom severity (assessed by ESSDAI and ESSPRI), quality of life (assessed by EQ-5D-5L), salivary gland and tear gland tests, laboratory immune markers, and safety parameters.