What can I take instead of hydroxychloroquine for Sjögren's?

October 11, 2025 •

4 min read

An estimated 4 million people worldwide are affected by Sjögren's disease, and for those who find hydroxychloroquine (Plaquenil) ineffective or intolerable, there are several viable alternatives available. Addressing the complex nature of this autoimmune condition often requires exploring different medications to manage symptoms and disease activity effectively.

Quick Summary

Alternative treatments for Sjögren's syndrome, when hydroxychloroquine is unsuitable, include other disease-modifying antirheumatic drugs (DMARDs), biologics, corticosteroids, and medications targeting specific sicca symptoms like dry eyes and dry mouth.

Key Points

DMARDs and Biologics: Methotrexate, leflunomide, azathioprine, and biologics like rituximab are systemic alternatives to hydroxychloroquine, especially for managing joint pain and organ involvement.
Targeted Sicca Relief: For dry mouth and eyes, pilocarpine and cevimeline stimulate secretions, while prescription eye drops like cyclosporine and lifitegrast reduce inflammation.
Symptom-Specific Medications: Oral medications and eye drops are effective for managing the dry eye and dry mouth symptoms that are hallmarks of Sjögren's.
Steroids for Flares: Short-term use of corticosteroids like prednisone can quickly address severe flare-ups of inflammation but are not suitable for long-term use due to side effects.
Investigational Therapies: New treatments like nipocalimab, an FcRn blocker, are under investigation and show promise for patients with moderate-to-severe Sjögren's.
Personalized Treatment: The best alternative depends on individual symptoms and severity, requiring close consultation with a rheumatologist to find a suitable, personalized treatment plan.
Complementary Therapies: While scientific evidence is limited, some complementary approaches like Omega-3 fatty acids may be considered alongside conventional care.

Hydroxychloroquine (HCQ) is a common initial treatment for Sjögren's syndrome, often used to manage symptoms like joint pain, fatigue, and rashes. However, it may not be effective for all patients, and some may experience side effects or need a stronger therapy. When HCQ proves insufficient, a healthcare provider may explore other medication classes to control the autoimmune response and alleviate symptoms.

Systemic Disease-Modifying Agents

Beyond hydroxychloroquine, several other disease-modifying antirheumatic drugs (DMARDs) and biologics can target the underlying inflammation and overactive immune system in Sjögren's syndrome.

Conventional DMARDs

For patients with significant joint or muscle pain who do not respond to HCQ, other conventional DMARDs may be considered.

Methotrexate (Trexall®, Rheumatrex®): This immunosuppressant is used to treat inflammatory joint pain associated with Sjögren's syndrome. It is often prescribed when HCQ is ineffective. However, it is a potent medication with a different side effect profile than HCQ and requires regular monitoring by a rheumatologist.
Leflunomide (Arava®): This DMARD can be an option if HCQ or methotrexate alone are not effective for inflammatory musculoskeletal pain. It modifies immune system activity and is also used for other autoimmune conditions.
Azathioprine (Imuran®) and Mycophenolate Mofetil (Cellcept®): These more potent immunosuppressants are reserved for more severe cases of Sjögren's, particularly those with major organ involvement such as the lungs or kidneys.

Biologics

Biologic therapies target specific components of the immune system and are typically reserved for patients with severe systemic complications.

Rituximab (Rituxan®): This medication targets and depletes B-cells, which are overactive in Sjögren's. It is used for specific severe manifestations, including vasculitis, lymphoma, and severe parotid swelling. It is administered via intravenous (IV) infusion.
Belimumab (Benlysta®): Another B-cell modulating therapy, belimumab has shown promise for certain autoimmune conditions and is sometimes used in Sjögren's, although it is not specifically FDA-approved for this condition. It can be administered as an IV infusion or a subcutaneous self-injection.

Symptom-Specific Medications

For many patients, especially those who primarily experience dryness, treatment focuses on managing the specific symptoms of dry eyes and dry mouth.

Dry Eye Treatment

Prescription Eye Drops: For moderate to severe cases, ophthalmologists can prescribe anti-inflammatory drops like cyclosporine (Restasis®, Cequa™) or lifitegrast (Xiidra®), which help decrease inflammation in the tear glands to increase tear production.
Punctal Plugs: These tiny, dissolvable or permanent plugs are inserted into the tear ducts to block drainage and keep natural tears on the eye's surface longer.
Other Options: In severe cases, autologous serum eye drops (made from a patient's own blood) can help heal surface damage.

Dry Mouth Treatment

Cholinergic Agonists: Oral medications like pilocarpine (Salagen®) and cevimeline (Evoxac®) stimulate the salivary glands to produce more saliva and can also benefit dry eyes. Side effects can include increased sweating and nausea.
Artificial Saliva: Numerous over-the-counter products are available to help moisten and lubricate the mouth.

Corticosteroids and NSAIDs

Corticosteroids (e.g., prednisone): These powerful anti-inflammatory drugs are used for short-term management of severe flare-ups, such as significant joint pain or inflammation. Due to significant side effects with long-term use, doctors aim to use them for the shortest possible duration at the lowest effective dose.
Non-steroidal Anti-inflammatory Drugs (NSAIDs): Over-the-counter NSAIDs like ibuprofen or naproxen can help manage mild joint pain. They can be combined with other therapies for greater effect.

Comparison of Sjögren's Medications


Medication Type	Examples	Primary Target Symptoms	Administration	Key Considerations
DMARDs	Methotrexate, Leflunomide	Joint pain, systemic inflammation	Oral	Require regular monitoring; different side effect profiles
Biologics	Rituximab, Belimumab	Severe systemic manifestations (e.g., vasculitis)	IV Infusion, Subcutaneous	Potent immune suppression; reserved for severe cases
Cholinergic Agonists	Pilocarpine, Cevimeline	Dry mouth, dry eyes	Oral	Stimulate secretions; common side effect is sweating
Prescription Eye Drops	Cyclosporine, Lifitegrast	Moderate to severe dry eyes	Ophthalmic drops	Anti-inflammatory; can take weeks to months for full effect
Corticosteroids	Prednisone	Acute flares, severe inflammation	Oral	Quick-acting; used short-term due to side effects

Investigational Treatments

Ongoing research continues to develop new targeted therapies for Sjögren's. One promising investigational drug is nipocalimab, an FcRn blocker that reduces levels of inflammatory IgG autoantibodies. It has been granted FDA Breakthrough Therapy designation for moderate-to-severe Sjögren's disease. While not yet available, such developments offer hope for future treatment options.

Conclusion

For individuals with Sjögren's syndrome who need to find an alternative to hydroxychloroquine, a wide array of options exist. The appropriate medication depends on the specific symptoms, disease severity, and individual patient factors. Whether exploring a different DMARD like methotrexate, a biologic such as rituximab for systemic issues, or symptom-specific treatments like pilocarpine or cyclosporine eye drops, effective management is possible. The most crucial step is to work closely with a rheumatologist to develop a personalized treatment plan.

For more information on Sjögren's syndrome, consider consulting the resources provided by the Sjögren's Foundation.

Frequently Asked Questions

If hydroxychloroquine doesn't work for joint pain, your doctor may consider another conventional DMARD like methotrexate or leflunomide. In severe cases, or with major organ involvement, more potent immunosuppressants or biologics might be explored.

Yes, both cevimeline (Evoxac®) and pilocarpine (Salagen®) are cholinergic agonists that stimulate exocrine glands, including tear glands. While FDA-approved for dry mouth, some patients find they also provide relief for dry eyes.

Biologics are generally not a first-line alternative to hydroxychloroquine. They are typically reserved for patients with severe systemic manifestations of Sjögren's syndrome, such as vasculitis or significant organ involvement, that do not respond to other treatments.

These eye drops are anti-inflammatory. Cyclosporine (Restasis®) and lifitegrast (Xiidra®) work by targeting and reducing the inflammation in the tear-producing glands, which can lead to increased tear production over time.

While effective for controlling flares, long-term use of corticosteroids like prednisone carries significant risks, including cataracts, osteoporosis, weight gain, high blood pressure, and diabetes.

Yes, new investigational treatments are in development. For example, nipocalimab, a monoclonal antibody, has received FDA Breakthrough Therapy designation for moderate-to-severe Sjögren's disease and is currently in clinical trials.

In addition to medications, strategies include using artificial tears and saliva products, maintaining good oral hygiene, using vaginal lubricants, avoiding medications that worsen dryness, and dietary modifications. A doctor may also suggest procedures like punctal plugs for dry eyes.