Disclaimer: This article is for informational purposes only and does not constitute medical advice. The decision to change medication should always be made in consultation with a qualified healthcare professional, such as a rheumatologist.
Hydroxychloroquine (Plaquenil) is a cornerstone therapy for many autoimmune diseases, particularly systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [1.3.6]. It is an antimalarial drug that modulates the immune system to reduce inflammation and prevent disease flares [1.2.3, 1.2.6]. However, not everyone can tolerate Plaquenil due to side effects, or it may not be effective enough for their condition. Common reasons for seeking an alternative include side effects like gastrointestinal issues, skin rashes, and the small but serious risk of retinal damage with long-term use [1.3.4, 1.8.3].
Understanding the Alternatives: DMARDs and Biologics
When considering what to take instead of Plaquenil, the options generally fall into several categories of Disease-Modifying Antirheumatic Drugs (DMARDs). These medications work to slow or stop the underlying disease process [1.9.5].
Conventional Synthetic DMARDs (csDMARDs)
This class of drugs is often the next step if Plaquenil is not suitable. They are broad immunosuppressants [1.2.6].
- Methotrexate (Trexall, Rheumatrex): Often considered a first-line treatment for RA, methotrexate is a powerful anti-inflammatory drug [1.6.6]. It is also used in lupus [1.2.4]. It works by interfering with folic acid, which slows down the growth of certain cells, including those in the immune system [1.2.5]. Due to its potency, regular blood monitoring is required to check for liver toxicity and bone marrow suppression [1.9.3].
- Sulfasalazine (Azulfidine): This medication is commonly used for rheumatoid arthritis and has anti-inflammatory properties [1.2.1]. Its exact mechanism is not fully understood, but it is known to affect the immune system. Efficacy is considered similar to or slightly less than methotrexate in some studies [1.4.1].
- Leflunomide (Arava): Leflunomide is another option for RA that works by inhibiting an enzyme involved in the production of immune cells [1.4.1]. Its effectiveness is comparable to methotrexate, but it may have a different side effect profile, including a higher risk of elevated blood pressure [1.4.1, 1.4.5].
- Azathioprine (Imuran): This is an immunosuppressive drug used for more severe cases of lupus and RA when other treatments have failed [1.2.4, 1.2.6]. It curbs the immune system to prevent organ damage [1.2.4].
Biologic DMARDs (bDMARDs)
Biologics are a newer class of drugs created from living cells. They are more targeted than csDMARDs, blocking specific proteins or cells in the immune system responsible for inflammation [1.9.5].
- Belimumab (Benlysta): Approved specifically for SLE and lupus nephritis, Benlysta targets and blocks the activity of B-cells, a type of white blood cell that produces harmful autoantibodies in lupus patients [1.5.2, 1.5.3]. It is available as an IV infusion or a subcutaneous injection [1.2.6].
- Anifrolumab (Saphnelo): Also approved for moderate to severe SLE, Saphnelo works differently by blocking the type I interferon receptor [1.5.2]. The interferon system is a key driver of inflammation in many lupus patients [1.5.5]. It is administered as an IV infusion every four weeks [1.5.5].
- TNF Inhibitors (e.g., Adalimumab/Humira, Etanercept/Enbrel): This group of biologics is widely used for RA. They work by blocking Tumor Necrosis Factor (TNF), a key cytokine that promotes inflammation [1.6.4].
Targeted Synthetic DMARDs (tsDMARDs) / JAK Inhibitors
This is the newest class of oral medications for autoimmune diseases, primarily RA. They work inside the cell to disrupt inflammatory signaling pathways [1.6.2].
- Tofacitinib (Xeljanz), Baricitinib (Olumiant), Upadacitinib (Rinvoq): These oral pills block Janus kinase (JAK) enzymes, which are crucial for the signaling of many inflammatory cytokines [1.6.4]. They can be effective for patients who haven't responded to csDMARDs or even biologics [1.6.2]. However, they carry specific warnings regarding an increased risk of serious infections, heart-related events, and certain cancers [1.6.4].
Comparison of Common Plaquenil Alternatives
| Medication (Brand Name) | Primary Condition(s) | Mechanism (Simplified) | Common Side Effects | Monitoring Required |
|---|---|---|---|---|
| Methotrexate (Trexall) | RA, Lupus [1.2.5] | Folic acid antagonist, slows immune cell growth [1.2.5] | Nausea, mouth sores, fatigue, liver enzyme elevation [1.2.5] | Regular blood tests for liver, kidneys, and blood counts [1.9.3] |
| Sulfasalazine (Azulfidine) | RA [1.2.1] | Immune modulator | Upset stomach, rash, headache [1.8.1, 1.4.1] | Blood tests initially, then less frequently [1.9.2] |
| Leflunomide (Arava) | RA [1.2.1, 1.2.6] | Inhibits immune cell production [1.4.1] | Diarrhea, hair loss, elevated blood pressure, liver issues [1.4.1, 1.4.3] | Blood pressure checks, regular blood tests for liver and blood counts [1.9.2] |
| Belimumab (Benlysta) | Lupus, Lupus Nephritis [1.2.6] | B-cell inhibitor [1.5.2] | Nausea, diarrhea, infections, infusion reactions [1.2.6, 1.5.3] | Monitoring for infection, hypersensitivity reactions [1.5.2] |
| Anifrolumab (Saphnelo) | Lupus [1.2.4] | Type I interferon receptor antagonist [1.5.2] | Upper respiratory infections, infusion reactions, shingles [1.5.2, 1.5.3] | Monitoring for infection, infusion reactions [1.5.2] |
| Tofacitinib (Xeljanz) | RA [1.6.3] | JAK inhibitor [1.6.2] | Upper respiratory infections, headache, diarrhea [1.6.6] | Blood tests for lipids, liver function, and blood counts [1.9.3] |
Conclusion
Deciding what to take instead of Plaquenil is a significant medical decision that requires careful consideration of your specific diagnosis, disease activity, other health conditions, and personal preferences. Options range from well-established conventional DMARDs like methotrexate to highly targeted biologics like Benlysta and Saphnelo for lupus, and powerful oral JAK inhibitors for rheumatoid arthritis [1.2.1, 1.6.1]. Each alternative carries its own unique profile of benefits, risks, and monitoring requirements [1.9.2]. The most critical step is an open and thorough discussion with your rheumatologist to determine the safest and most effective path forward for your health.
For more information on managing autoimmune diseases, a valuable resource is the Arthritis Foundation [1.9.5].
