Plaquenil (hydroxychloroquine) is frequently used as a first-line therapy for the joint pain, fatigue, and rashes associated with Sjogren's syndrome [1.2.3, 1.3.4]. However, due to ineffectiveness for some patients or concerns about side effects like retinal damage, many seek alternatives [1.4.5]. Treatment for Sjogren's is highly dependent on which parts of the body are affected, and a rheumatologist will guide the therapeutic decisions [1.3.1, 1.8.2].
Why Seek an Alternative to Plaquenil?
While recommended by the Sjogren's Foundation as a first-line therapy for inflammatory musculoskeletal pain, Plaquenil's efficacy is not universally established and can be debated in the medical community [1.2.3]. Some randomized controlled trials have suggested it has no significant effect compared to a placebo for certain aspects of the disease [1.2.3]. The primary reasons a patient and their doctor might explore other options include:
- Lack of Efficacy: The medication may not adequately control a patient's joint pain, fatigue, or other systemic symptoms [1.2.3].
- Side Effects: The most notable side effect is the risk of retinal toxicity, which requires regular eye exams [1.4.5]. Other adverse effects can also occur.
- Disease Progression: The disease may progress to affect major organs, requiring stronger medications that suppress the immune system more aggressively [1.3.1, 1.4.5].
Symptom-Specific Treatments
For many patients, the most burdensome symptoms are severe dryness. These are often treated independently of systemic medications.
Medications for Dry Mouth (Xerostomia)
To combat dry mouth and reduce the risk of dental cavities, doctors may prescribe medications that stimulate saliva production [1.3.2]. These are known as cholinergic agonists.
- Pilocarpine (Salagen): This drug can increase saliva production but may cause side effects like sweating and increased urination [1.3.2, 1.7.5].
- Cevimeline (Evoxac): An alternative to pilocarpine, cevimeline also boosts saliva but can be associated with side effects such as nausea and sweating [1.7.2, 1.7.3].
Medications for Dry Eyes (Keratoconjunctivitis Sicca)
For moderate to severe dry eyes, over-the-counter artificial tears may not be enough. Prescription eye drops can help by reducing inflammation or increasing tear production [1.3.2].
- Cyclosporine (Restasis): These prescription eye drops decrease eye inflammation, helping to increase tear production [1.3.2].
- Lifitegrast (Xiidra): This is another option for prescription eye drops that can be recommended by an eye doctor for dry eyes [1.3.1, 1.3.2].
Systemic Treatments Beyond Plaquenil
When Sjogren's involves systemic inflammation, such as arthritis, or affects internal organs, a more potent immunomodulatory approach is needed. These medications are often categorized as Disease-Modifying Antirheumatic Drugs (DMARDs).
Immunosuppressive DMARDs
These medications work by suppressing the overactive immune system [1.2.4].
- Methotrexate (Trexall): Often prescribed if joint pain is severe and unresponsive to Plaquenil, methotrexate is effective in treating inflammation [1.4.5, 1.4.6]. It requires regular monitoring by a rheumatologist due to potential side effects, including liver damage [1.4.5].
- Azathioprine (Imuran): This is another immunosuppressant used for more severe, systemic manifestations of the disease [1.3.1, 1.4.5].
- Mycophenolate (CellCept) and Leflunomide: These are other steroid-sparing immunosuppressants that may be considered by a specialist [1.3.1, 1.3.3].
Biologic Therapies (Biologic DMARDs)
Biologics are a newer class of DMARDs that target specific parts of the immune system. They are generally reserved for patients with more severe, active systemic disease [1.3.6].
- Rituximab (Rituxan): This biologic therapy targets and depletes B-cells, a type of white blood cell central to the autoimmune process in Sjogren's [1.2.7, 1.5.3]. While some large trials have failed to meet their primary endpoints, other studies and clinical experience suggest it can be effective for certain extraglandular features, such as vasculitis, and may be used in severe cases [1.5.1, 1.5.2, 1.4.5].
- Belimumab (Benlysta): This biologic targets a protein called B-lymphocyte stimulator (BLyS), which is elevated in Sjogren's patients. It has shown benefits for some systemic symptoms [1.5.1, 1.5.5]. Sometimes, it is even used sequentially with rituximab [1.5.4].
Comparison of Plaquenil Alternatives
| Medication | Class | Primary Target | Administration | Common Side Effects | Monitoring |
|---|---|---|---|---|---|
| Methotrexate | Immunosuppressant | Joint inflammation | Oral or injection | Nausea, hair loss, mouth sores, liver damage [1.4.5] | Regular blood tests for liver function and blood counts [1.4.5] |
| Rituximab | Biologic DMARD | CD20 on B-cells | Intravenous (IV) infusion | Infusion reactions, infections [1.5.2, 1.5.3] | Monitoring during infusion and for signs of infection [1.5.2] |
| Belimumab | Biologic DMARD | B-lymphocyte stimulator (BLyS) | Intravenous (IV) or subcutaneous | Nausea, diarrhea, infections, infusion reactions [1.5.1] | Monitoring for mood changes and infections [1.5.1] |
| Cevimeline | Cholinergic Agonist | Salivary glands | Oral capsule | Sweating, nausea, runny nose [1.7.3] | Caution with certain heart conditions or asthma [1.7.3] |
Conclusion
Choosing an alternative to Plaquenil for Sjogren's syndrome is a collaborative decision between a patient and their rheumatologist [1.8.2]. The best option depends entirely on the individual's specific symptoms—whether they are glandular (dryness) or systemic (joint pain, organ involvement)—as well as their tolerance for potential side effects and the severity of their disease. While dryness can be managed with targeted drugs like pilocarpine and cyclosporine, systemic symptoms often require more powerful immunosuppressants like methotrexate or targeted biologic therapies such as rituximab [1.3.1].
For more information, you can visit the Sjögren's Foundation.
