Abatacept Fails Clinical Trial for Sjögren’s Syndrome

March 24, 2020

The use of abatacept did not lead to significant improvements in the disease status of patients with primary Sjögren's syndrome and in fact, it was essentially no better than placebo treatment, shows the first randomized, double-blind trial on abatacept for Sjögren’s.

The use of abatacept (Orencia, Bristol-Myers Squibb) did not lead to significant improvements in the disease status of patients with primary Sjögren's syndrome and in fact, it was essentially no better than placebo treatment, shows the first randomized, double-blind trial on abatacept for Sjögren’s patients.

Patients with for Sjögren’s syndrome can exhibit an array of symptoms including glandular enlargement, sicca symptoms, disabling fatigue, arthritis, skin involvement, renal and lung involvement, and peripheral neuropathy. There is no approved systemic treatment for the condition and today, the standard treatment is limited to treating symptoms.

Now, the results of a new study, which was recently published in the Lancet Rheumatology, suggests this may be “the end of the road for abatacept treatment in Sjögren's syndrome,” according to Benjamin A. Fisher, M.D., a rheumatologist with the University of Birmingham, England. In an editorial Dr. Fisher wrote in response to the findings, he described both the condition and the study’s findings complex. “Unless future analyses reveal clear histological improvement or subgroups enriched for abatacept response, it is hard to see a way forward for abatacept in Sjögren's syndrome,” he wrote.

Previous small open-label studies in primary Sjögren’s syndrome have suggested efficacy of abatacept, a co-stimulation inhibitor, including improvements in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI), the European League Against Rheumatism Patient Reported
Index (ESSPRI), fatigue, salivary flow, and health-related quality of life.

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The study, called ASAP-III which was led by Hendrika Bootsma, Ph.D., of the University of Groningen, the Netherlands, included 80 patients (mean age 49 years) who were randomly assigned to receive subcutaneous injections of abatacept (125 mg) or placebo once a week for 24 weeks. Patients had positive salivary gland biopsies, an ESSDAI score of 5 or more, and a time since diagnosis of seven years or less.

The primary outcome, which was the between-group difference in ESSDAI score at week 24, was not met.

Abatacept was well tolerated by treated patients with no serious treatment-related serious adverse events. Nor did they have a higher prevalence of infections.

No significant differences in ESSPRI score were found between the groups. Sexual function in females was improved with abatacept, but no improvement was seen for dryness symptoms, fatigue, quality of life, and salivary and tear gland function.

“On the basis of this trial, we cannot recommend abatacept treatment as standard of care to reduce systemic disease activity in patients with primary Sjögren's syndrome. Further studies should evaluate whether patients with specific clinical manifestations and biological characteristics might benefit from abatacept treatment,” Dr. Bootsma and colleagues wrote.

REFERENCE

Jolien F van Nimwegen, Esther Mossel, Greetje S van Zuiden, et al. “Abatacept treatment for patients with early active primary Sjögren's syndrome: a single-centre, randomised, double-blind, placebo-controlled, phase 3 trial (ASAP-III study).”The Lancet Rheumatology. January 31, 2020. DOI:https://doi.org/10.1016/S2665-9913(19)30160-2

Benjamin A Fisher.“Is it the end of the road for abatacept treatment in Sjögren's syndrome?” The Lancet Rheumatology. January 31, 2020. DOI:https://doi.org/10.1016/S2665-9913(20)30002-3