Understanding the Evolving Sjögren’s Disease Landscape

Sjögren’s disease spent decades without a successful targeted therapy, and the reasons trace back to how trials were designed as much as to the biology of the disease.

In this Special Report series, Nehad Soloman, MD, FACR, of Arizona Arthritis and Rheumatology Associates, spoke with Teja Kapoor, MD, director of the Columbia Sjögren’s Center, about why treatment has lagged.

Heterogeneity stands out as the central obstacle. Trials have grouped patients with distinct underlying disease mechanisms under a single diagnosis, diluting any treatment signal.¹ Many enrolled patients also carried longstanding glandular damage unlikely to recover even with successful immunosuppression.

Outcome measures have evolved alongside the field. Trials have relied on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and its clinical version, the ClinESSDAI.² European investigators have since proposed the STAR composite index as a newer alternative.³

Patient-reported outcomes pose a separate problem. Fatigue and other constitutional symptoms in many patients may stem from coexisting thyroid disease or fibromyalgia, which an immunomodulating agent would not be expected to treat. Measures such as the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) cannot distinguish these sources.

The trajectory mirrors lupus, where more than 5 decades passed before an advanced therapy met its trial end points. Better patient selection and refined composite end points now appear central to whether the current wave of Sjögren’s disease agents reaches approval.

References

1. Soyfoo M, Sarrand J, Delporte C. From molecular pathophysiology to clinical trial design in Sjögren’s disease: a three-axis framework. Int J Mol Sci. 2026;27(13):5692. doi:10.3390/ijms27135692

2. Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis. 2010;69(6):1103-1109. doi:10.1136/ard.2009.110619

3. Seror R, Baron G, Camus M, et al. Development and preliminary validation of the Sjögren’s Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren’s syndrome. Ann Rheum Dis. 2022;81(7):979-989. doi:10.1136/annrheumdis-2021-222054