What is the general approach to treating Sjögren's?
Treating Sjögren's works differently from treating rheumatoid arthritis or lupus. In some rheumatic diseases, we have specific disease-modifying drugs. For example, almost everyone with rheumatoid arthritis starts on one. Sjögren's is different. We look at your specific symptoms and choose treatments aimed at those symptoms.
The most common and most bothersome symptoms are dryness, fatigue, and brain fog.
Some people with Sjögren's also have symptoms that affect other parts of the body. These include arthritis, nerve problems (neuropathy), skin disease, kidney or lung disease, and swollen glands. We look at these separately and call them systemic features of Sjögren's.
Why separate systemic features from the symptoms you feel day to day?
When we choose or evaluate a treatment, we need to know which symptoms it actually treats. No single drug treats every part of Sjögren's. A drug that calms inflammation in the joints or lungs may do nothing for dry eyes or fatigue, and the reverse is also true.
What drugs are FDA-approved for Sjögren's?
Only two drugs are FDA-approved specifically for Sjögren's: pilocarpine and cevimeline. Both treat dry mouth and dry eyes by stimulating the glands that make saliva and tears. They work best when the glands still have some function left. Common side effects include sweating, flushing, needing to urinate more often, and stomach upset. Starting at a low dose and increasing slowly helps.
No drug that changes the immune system is FDA-approved for Sjögren's yet. Rheumatologists often use other medications "off-label," meaning they are approved for other conditions. These include:
Hydroxychloroquine, often used for joint pain and some skin and blood findings
Steroids (glucocorticoids), usually for short periods
Cyclosporine eye drops, for dry eye
Rituximab, for severe systemic disease that has not responded to other treatments
How do we measure whether a new drug works?
Clinical trials use different scoring systems. Knowing which score a drug improved tells you which kind of benefit to expect.
ESSDAI (systemic disease activity): Your doctor fills this out. It scores inflammation across 12 areas of the body: general symptoms such as fever and weight loss, lymph nodes, gland swelling, joints, skin, lungs, kidneys, muscles, nerves, blood counts, and blood test markers. An improved ESSDAI means the drug helped systemic disease. It does not necessarily mean it helped dryness or fatigue.
ESSPRI (symptoms you feel): You fill this out. You rate three symptoms from 0 to 10: dryness, fatigue, and joint or muscle pain. A drop of about 1 point or 15% is considered a meaningful improvement.
SSSD (Sjögren's Syndrome Symptom Diary): You fill this out. It splits dryness up by location (eyes, mouth, skin, and for women, genital dryness), and also rates tiredness and muscle or joint pain.
Brain fog is not measured directly by any of these scores, even though many patients rank it among their most important symptoms.
What are the newest drugs in late-stage (phase 3) trials?
None of these drugs are FDA-approved for Sjögren's yet. So far, the main pattern is clear: most new drugs improve systemic disease (ESSDAI), while improvement in dryness and fatigue has been inconsistent.
Ianalumab (injection under the skin, monthly)
How it works: Lowers B cells (immune cells that make antibodies) and blocks a signal called BAFF that keeps them alive
Systemic benefit (ESSDAI): Yes, but small. ESSDAI improved by about 1 point more than placebo in two large phase 3 trials (NEPTUNUS-1 and -2)
Symptom benefit (ESSPRI / SSSD / fatigue): No. ESSPRI, SSSD, and fatigue did not improve compared with placebo. Saliva production improved in an earlier phase 2 study
Where it stands: First phase 3 results published in 2026 (Mariette et al., New England Journal of Medicine)
Deucravacitinib (pill)
How it works: Blocks TYK2, an enzyme that relays interferon and other inflammatory signals
Systemic benefit (ESSDAI): Being tested. ESSDAI is the main goal of the phase 3 trial
Symptom benefit (ESSPRI / SSSD / fatigue): No results yet in Sjögren's
Where it stands: Phase 3 trial ongoing
Telitacicept (injection)
How it works: Blocks two B-cell survival signals, BAFF and APRIL
Systemic benefit (ESSDAI): Yes at one dose (160 mg) in phase 2; the higher dose did not work
Symptom benefit (ESSPRI / SSSD / fatigue): Fatigue improved at both doses tested
Where it stands: Phase 3 ongoing
Dazodalibep (infusion)
How it works: Blocks CD40L, a signal that lets immune T cells activate B cells
Systemic benefit (ESSDAI): Yes, in patients with higher systemic activity
Symptom benefit (ESSPRI / SSSD / fatigue): Yes. ESSPRI (dryness, fatigue, pain) improved in patients with heavy symptoms but low systemic activity. Saliva production did not improve
Where it stands: Phase 3 ongoing
What this means for you
If your main problems are systemic (joints, lungs, nerves, glands, blood counts), look at a drug's ESSDAI results.
If your main problems are dryness, fatigue, or pain, look at its ESSPRI or SSSD results. So far, telitacicept (fatigue) and dazodalibep (overall symptoms) have shown the most promise there, but these are earlier-stage results and need confirmation in phase 3.
Ianalumab is an important first step. It is the first targeted drug to show benefit on systemic activity in phase 3, but it did not improve how patients felt day to day (Mariette et al., New England Journal of Medicine, 2026).
What does a rheumatologist consider when choosing treatment?
Which symptoms bother you most, and whether they are mainly dryness and fatigue or systemic features
Which organs are involved, and how severe the involvement is
What the evidence shows each drug improves: ESSDAI, ESSPRI, or SSSD
Side effects, safety, and your other health conditions
Whether a clinical trial might be a good option for you
Talk with your rheumatologist about which of your symptoms matter most to you. That conversation is the starting point for choosing the right treatment.