Systemic Lupus Erythematosus (SLE) Medication

Updated: Jun 16, 2022
  • Author: Christie M Bartels, MD, MS; Chief Editor: Herbert S Diamond, MD  more...
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Medication Summary

Treatment of systemic lupus erythematosus (SLE) is guided by the individual patient's manifestations. Fever, rash, musculoskeletal manifestations, and serositis generally respond to treatment with hydroxychloroquine, nonsteroidal anti-inflammatory drugs (NSAIDS), and steroids in low to moderate doses, as necessary, for acute flares. Medications such as methotrexate may be useful in chronic lupus arthritis, and azathioprine and mycophenolate have been widely used in lupus of moderate severity. [174]

Central nervous system or kidney involvement constitutes more serious disease and often requires high-dose steroids and other immunosuppressive agents, such as cyclophosphamide, azathioprine, or mycophenolate. Class IV diffuse proliferative lupus nephritis has also been treated with aggressive cyclophosphamide induction therapy. [175, 176] Trials of mycophenolate induction therapy have also demonstrated efficacy, particularly in black patients. [177, 178, 179] Rituximab trials, however, have not documented a benefit. [139, 140]  For lupus nephritis maintenance, the MAINTAIN trial offered data showing no statistically significant difference between mycophenolate and azathioprine. [153]



Class Summary

Antimalarial agents may work through numerous proposed mechanisms in SLE, mediating subtle immunomodulation without causing overt immunosuppression. These drugs are useful in preventing and treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis; antimalarials also help to prevent lupus flares and have been associated with reduced morbidity and mortality in SLE patients followed in observational trials. [115]

Hydroxychloroquine sulfate (Plaquenil)

Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate. Weight-based dose adjustment and monitoring help to mitigate the risk of retinal toxicity. This agent is also commonly used for suppression and treatment of malaria.



Class Summary

Nonsteroidal anti-inflammatory agents (NSAIDS) provide symptomatic relief for arthralgias, fever, headache, and mild serositis. NSAIDs may cause elevated creatinine or liver function test results in patients with active systemic lupus erythematosus. Additionally, concomitant administration with prednisone may increase the risk of gastrointestinal ulceration.

Ibuprofen (Advil, Motrin)

Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Aleve, Anaprox, Naprosyn)

Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of the enzyme cyclooxygenase, resulting in prostaglandin synthesis.

Diclofenac (Voltaren XR, Cataflam)

Diclofenac inhibits prostaglandin synthesis by decreasing activity of enzyme cyclo-oxygenase, which in turn decreases formation of prostaglandin precursors.


DMARDS, Immunomodulators

Class Summary

Disease-modifying antirheumatic drugs (DMARDS) are immunomodulatory agents that act as immunosuppressives and cytotoxic and anti-inflammatory medications. The specific agent selection is generally indicated by the patient’s organ involvement and disease severity. Due to toxicity, cyclophosphamide is reserved for severe organ-threatening disease. At the other end of the spectrum, methotrexate or azathioprine may be helpful for milder arthritis or skin disease. DMARDS can be used in patients whose condition has had an inadequate response to glucocorticoids. Azathioprine, mycophenolate, and cyclosporine have all been studied for lupus manifestations such as nephritis.


Cyclophosphamide is used for immunosuppression in cases of serious SLE organ involvement, especially severe CNS involvement, vasculitis, and lupus nephritis. This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Methotrexate (Otrexup, Rasuvo)

Methotrexate is used for managing arthritis, serositis, cutaneous, and constitutional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation and is particularly useful in arthritis treatment.

Azathioprine (Imuran, Azasan)

Azathioprine is an immunosuppressant and a less toxic alternative to cyclophosphamide. It is used as a steroid-sparing agent in nonrenal disease. Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity.

Mycophenolate (CellCept, Myfortic)

Mycophenolate is useful for maintenance in lupus nephritis and other serious lupus cases. This agent inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Mycophenolate also inhibits antibody production.

Immune globulin IV (IGIV) (Bivigam, Carimune, Gammagard S/D, Flebogamma, Gamunex-C)

Intravenous immune globulin is used for immunosuppression in serious SLE flares. It neutralizes circulating myelin antibodies through anti-idiotypic antibodies. This agent downregulates proinflammatory cytokines, including interferon-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells; and augments suppressor T cells. Immune globulin also blocks complement cascade, promotes remyelination, and may increase cerebrospinal fluid IgG (10%).


Rheumatologics, Other

Class Summary

Rheumatologic agents such belimumab reduce immune response and B-cell mediated immunity.

Belimumab (Benlysta)

Belimumab inhibits the biologic activity of B-lymphocyte stimulator (BLyS); BLyS is a naturally occurring protein required for survival and for development of B-lymphocyte cells into mature plasma B cells that produce antibodies. In autoimmune diseases, elevated BLyS levels are thought to contribute to production of autoantibodies.

This agent is indicated for active, autoantibody-positive SLE that is refractory to standard therapy including hydroxychloroquine (see Treatment for more details).



Class Summary

Corticosteroid agents are used predominantly for anti-inflammatory activity and as immunosuppressants. Preparations include oral, intravenous, topical, and intra-articular injections.

Methylprednisolone (A-Methapred, Medrol, Solu-Medrol, Depo-Medrol)

Methylprednisolone is used for acute organ-threatening exacerbations. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.


Prednisone is an immunosuppressant for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Low-dose oral prednisone can be used for milder SLE, but more severe involvement necessitates high doses of oral or intravenous therapy.


DMARDs, Other

Class Summary

Rituximab is a monoclonal antibody and an immunosuppressant that eliminates mature circulating B-cells.

Rituximab (Rituxan)

B-cell depletion with rituximab has been used successfully for rheumatoid arthritis, but it has shown mixed results for the treatment of SLE. One open study using rituximab reported excellent results as rescue therapy for patients with active SLE who were unresponsive to standard immunosuppressant therapy. However, 2 large placebo-controlled studies failed to show an overall significant response. Note that rituximab has an off-label indication for SLE.


Interferon Antagonists

Anifrolumab (Anifrolumab-fnia, Saphnelo)

Anifrolumab is a human monoclonal antibody to type I interferon receptor subunit 1 that suppresses interferon gene signatures and substantially reduced SLE disease activity. It is ndicated for the treatment of moderate-to-severe SLE.