Sjögren’s Syndrome

Overview

Sjögren’s syndrome, increasingly called Sjögren’s disease (SjD), is a chronic autoimmune condition in which the immune system attacks moisture-producing glands, most visibly causing dry eyes and dry mouth. It can also cause fatigue, pain, dental and eye complications, and inflammation in organs such as the lungs, kidneys, nerves, skin, and blood vessels. It affects women far more often than men, has highly variable severity, and carries a meaningful—though still minority—lifetime risk of B-cell lymphoma. BSR management guideline

There is no established cure, and as of October 28, 2026, there are no FDA-approved medicines specifically for Sjögren’s disease. Standard care therefore combines eye and mouth lubrication and protection, dental prevention, topical anti-inflammatory eye treatment when needed, fatigue and pain management, and individualized immune-suppressing treatment for significant organ involvement; routine long-term systemic steroids are not recommended. BSR management guideline Amgen Phase 3 announcement

Scope of Recent Research (2020–present)

Research since 2020 has become substantially more active and more biologically targeted, with investigators focusing on abnormal B cells, autoantibodies, T-cell/B-cell communication, inflammatory signaling, and ways to restore immune tolerance rather than only relieve dryness. The field is now producing positive randomized trials, including Phase 3 results, but these therapies are best described as potential disease-modifying treatments—not cures—because durable drug-free remission, restoration of damaged glands, and prevention of all long-term complications have not yet been demonstrated. Ianalumab Phase 3 trials NIAMS Sjögren’s research overview

Major Breakthroughs and Emerging Therapies

The strongest recent advance is targeted B-cell therapy. Ianalumab is an antibody that both blocks the B-cell activating factor receptor (BAFF-R) and depletes B cells. In the two randomized Phase 3 NEPTUNUS trials, monthly subcutaneous ianalumab produced statistically significant improvements in systemic disease activity at week 48 versus placebo. These are the first published successful Phase 3 trials of a targeted treatment in Sjögren’s disease, although the average differences in disease-activity scores were modest and the treatment was still investigational in the United States as of October 28, 2026. Ianalumab Phase 3 trials FDA Breakthrough Therapy update

A second major strategy interrupts CD40-CD40 ligand signaling, an immune “conversation” needed for coordinated activation of T cells, B cells, and antigen-presenting cells. In a Phase 2 randomized trial, the CD40-ligand blocker dazodalibep improved systemic disease activity in participants with active systemic disease and improved patient-reported dryness, fatigue, and pain in a separate high-symptom group. In September 2026, Amgen reported that the Phase 3 OASIZ 301 trial met its week-48 primary endpoint for systemic disease activity; detailed peer-reviewed Phase 3 data were not yet available. Dazodalibep Phase 2 trial Dazodalibep Phase 3 topline results

Other approaches aim to lower harmful antibodies or dampen intracellular immune signals. Nipocalimab blocks the neonatal Fc receptor (FcRn), which normally protects immunoglobulin G antibodies from breakdown; its Phase 2 DAHLIAS trial tested whether reducing circulating IgG, including autoantibodies, can reduce Sjögren’s activity. The oral Bruton tyrosine kinase inhibitor remibrutinib, which suppresses B-cell signaling, significantly improved systemic activity at 24 weeks in a Phase 2 trial but did not significantly improve the patient-reported symptom index. Low-dose interleukin-2, intended to expand immune-regulating T cells, improved disease activity and several clinical measures in a small randomized trial, providing an early signal that immune tolerance may be therapeutically adjustable. Nipocalimab DAHLIAS Phase 2 trial Remibrutinib Phase 2 trial Low-dose IL-2 randomized trial

Cell therapy is the most explicitly “curative” concept under exploration because it seeks a deeper immune-system reset. In a 2023 case report, a patient treated with CD19-directed CAR-T cells for aggressive lymphoma also had improvement in Sjögren’s activity, autoantibodies, and dry-mouth symptoms; however, one oncology case cannot establish that CAR-T cures Sjögren’s disease. Novartis subsequently initiated an early study of rapcabtagene autoleucel, a CD19 CAR-T product, in rheumatoid arthritis and Sjögren’s disease, but this remains experimental and must be weighed against the serious immune toxicities associated with CAR-T platforms. CAR-T Sjögren’s case report Rapcabtagene autoleucel study

Clinical Trials and Experimental Approaches

The most consequential recent clinical programs are Novartis’s Phase 3 NEPTUNUS-1 and NEPTUNUS-2 ianalumab studies, which tested monthly and, in one trial, every-three-month dosing in active disease; both met the primary endpoint of improved EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 48. Ianalumab received FDA Breakthrough Therapy designation in 2026 but had not received FDA approval by October 28, 2026. Ianalumab Phase 3 trials FDA Breakthrough Therapy update

Amgen’s dazodalibep program includes the completed Phase 2 trial, the positive Phase 3 OASIZ 301 systemic-disease study, the Phase 3 OASIZ 303 study in people with severe symptoms but lower systemic activity, and an open-label long-term safety extension. Johnson & Johnson’s Phase 2 DAHLIAS study of nipocalimab supplied proof-of-concept for FcRn inhibition, while remibrutinib and low-dose IL-2 remain examples of earlier-stage programs that produced encouraging but not definitive findings. Dazodalibep Phase 2 trial Dazodalibep Phase 3 program Nipocalimab DAHLIAS Phase 2 trial Remibrutinib Phase 2 trial

Methodologies and Scientific Approaches

Modern Sjögren’s trials increasingly separate people with measurable systemic inflammation from those whose dominant burden is dryness, pain, or fatigue, then use both clinician-scored disease activity measures such as ESSDAI and patient-reported measures such as ESSPRI. This approach reflects the disease’s biological and clinical diversity, but it also makes it harder to identify a single treatment that improves every manifestation for every patient. Dazodalibep Phase 2 trial NIAMS Sjögren’s research overview

Researchers are pairing trials with blood immune profiling, autoantibody and protein measurements, gene-expression studies, salivary-gland ultrasound, and minor salivary-gland biopsies. Patient-derived salivary-gland organoids—three-dimensional miniature gland models grown from biopsies—now offer a way to test inflammation and possible regenerative treatments in tissue that retains key disease features; a 2025 study found that the JAK inhibitor tofacitinib improved swelling behavior in Sjögren’s-derived organoids. Remibrutinib Phase 2 trial Patient-derived salivary-gland organoids BSR management guideline

Leading Institutions and Funding

Clinical leadership is distributed across academic rheumatology centers and biotechnology companies. The dazodalibep Phase 2 study included investigators from Duke University, Johns Hopkins, Newcastle University, the University of Kansas Medical Center, and European Sjögren’s centers alongside sponsor Amgen; Novartis funded the NEPTUNUS ianalumab trials. Research on patient-derived gland organoids includes teams at Université Paris-Saclay, Inserm, and Gustave Roussy. Dazodalibep Phase 2 trial Ianalumab Phase 3 trials Patient-derived salivary-gland organoids

In the United States, NIH-supported efforts include the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases program, which launched in 2021 with $58.5 million in five-year total project funding and includes Sjögren’s disease. The Sjögren’s Foundation supplements this ecosystem with Pilot Grants of $50,000 for one to two years and High Impact Grants of $100,000 for one to three years. AMP AIM program Sjögren’s Foundation research grants

Strengths, Limitations, and Challenges

The clearest strength of the current wave is biological precision: B-cell depletion or modulation, CD40-CD40L blockade, FcRn inhibition, kinase inhibition, and regulatory-T-cell enhancement each target plausible disease mechanisms and have produced randomized-trial signals. The ianalumab and dazodalibep programs particularly show that well-designed studies can detect improvements in systemic disease activity and, for dazodalibep, symptoms. Ianalumab Phase 3 trials Dazodalibep Phase 2 trial

Important limitations remain. Sjögren’s is biologically heterogeneous, existing damage to salivary and tear glands may not be reversible even if inflammation is controlled, and improvements in laboratory or systemic activity scores do not always translate into relief of dryness, fatigue, or pain. Immune-targeted drugs can increase infection risk, while CAR-T therapy adds risks such as cytokine-release syndrome, neurotoxicity, prolonged B-cell depletion, and other severe immune complications. Cost, infusion or monitoring requirements, trial eligibility restrictions, and uncertain insurance coverage could also limit access if therapies are approved. BSR management guideline CAR-T Sjögren’s case report Dazodalibep Phase 3 program

Outlook and Future Directions

As of October 28, 2026, Sjögren’s research is closer than it has been to its first approved disease-modifying medicines, especially following the positive Phase 3 ianalumab and dazodalibep results. A true cure remains distant: the necessary milestones are durable remission after treatment stops, meaningful recovery or replacement of damaged salivary and lacrimal tissue, prevention of organ damage and lymphoma, and evidence that benefits extend across disease subtypes. The most important near-term developments to watch are regulatory decisions on ianalumab, full peer-reviewed Phase 3 dazodalibep results, longer-term safety data for B-cell-directed treatments, and whether carefully controlled cellular or regenerative approaches can achieve sustained immune reset without unacceptable risk. Ianalumab Phase 3 trials Dazodalibep Phase 3 program Patient-derived salivary-gland organoids

References

• BSR management guideline — British Society for Rheumatology, 2024.
• Ianalumab Phase 3 trials — Bowman et al., 2026.
• Amgen Phase 3 announcement — Amgen, 2026.
• NIAMS Sjögren’s research overview — National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2026.
• FDA Breakthrough Therapy update — Sjögren’s Foundation, 2026.
• Dazodalibep Phase 2 trial — St. Clair et al., 2024.
• Dazodalibep Phase 3 topline results — Amgen, 2026.
• Nipocalimab DAHLIAS Phase 2 trial — The Lancet, 2025.
• Remibrutinib Phase 2 trial — Dörner et al., 2024.
• Low-dose IL-2 randomized trial — He et al., 2022.
• CAR-T Sjögren’s case report — Sheng et al., 2023.
• Rapcabtagene autoleucel study — Novartis, 2026.
• Patient-derived salivary-gland organoids — Meudec et al., 2025.
• AMP AIM program — National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2026.
• Sjögren’s Foundation research grants — Sjögren’s Foundation, 2026.