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Medication Summary Treatment of systemic lupus erythematosus (SLE) is guided by the individual pati ent's manifestations.

Fever, rash, musculoskeletal manifestations, and serositis generally respond to treatment with hydroxychloroquine, NSAIDS, and low-to-mode rate dose steroids, as necessary, for acute flares. Medications such as methotrexate may be useful in chronic lupus arthritis, and azathioprine and mycophenolate ha ve been widely used in moderate severity lupus. CNS involvement and renal disease constitute more serious disease and often requ ire high-dose steroids and other immunosuppression agents such as cyclophosphami de, azathioprine, or mycophenolate. Class IV diffuse proliferative lupus nephrit is has also been treated with aggressive cyclophosphamide induction therapy.[81, 82] Recent trials of mycophenolate have demonstrated efficacy for induction, pa rticularly in black patients.[83, 84, 85] Rituximab trials have shown modest ben efit to date.[67] The MAINTAIN trial offered data showing no statistically signi ficant difference between mycophenolate and azathioprine for lupus nephritis mai ntenance.[86] Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Class Summary These agents provide symptomatic relief for arthralgias, fever, and mild serosit is. NSAIDs may cause elevated creatinine or liver function test results in patie nts with active SLE. Additionally, concomitant administration with prednisone ma y increase risk of GI ulceration. View full drug information Ibuprofen (Advil, Motrin IB, Addaprin, Ibu, NeoProfen) Ibuprofen is the drug of choice for patients with mild-to-moderate pain. It inhi bits inflammatory reactions and pain by decreasing prostaglandin synthesis. View full drug information Naproxen (Anaprox, Naprelan, Naprosyn) Naproxen is used for relief of mild to moderate pain. It inhibits inflammatory r eactions and pain by decreasing activity of the enzyme cyclooxygenase, resulting in prostaglandin synthesis. View full drug information Diclofenac (Voltaren XR, Cataflam) Diclofenac inhibits prostaglandin synthesis by decreasing activity of enzyme cyc lo-oxygenase, which in turn decreases formation of prostaglandin precursors. Antimalarials Class Summary Antimalarials may work through numerous proposed mechanisms in SLE, mediating su btle immunomodulation without causing overt immunosuppression. They are useful i n preventing and treating lupus skin rashes, constitutional symptoms, arthralgia s, and arthritis. They also help to prevent lupus flares and have been associate d with reduced morbidity and mortality in SLE patients followed in observational trials.[68] View full drug information Hydroxychloroquine (Plaquenil) This agent inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulf ate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquin

e phosphate. Weight-based dose adjustment and monitoring help mitigate risk of r etinal toxicity.[87] Immunosuppressant Agents Class Summary These agents act as immunosuppressives and cytotoxic and anti-inflammatory agent s. Agent selection is generally indicated by organ involvement and 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 f or milder arthritis or skin disease. Azathioprine, mycophenolate, and cyclospori ne have all been studied in lupus manifestations such as nephritis. Griffiths et al compared the corticosteroid-sparing effect of cyclosporine with azathioprine in patients with severe SLE. The authors concluded that azathioprin e may be considered first-line therapy since cyclosporine requires close monitor ing of blood pressure and serum creatinine.[88] The MAINTAIN trial compared the efficacy of azathioprine and mycophenolate for lupus nephritis maintenance and s howed nonsignificant reduction in lupus flares with mycophenolate.[86] View full drug information Cyclophosphamide Cyclophosphamide is used for immunosuppression in cases of serious SLE organ inv olvement, especially severe CNS involvement, vasculitis, and lupus nephritis. Th is 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. View full drug information Methotrexate (Trexall, Rheumatrex) Methotrexate is used for managing arthritis, serositis, cutaneous, and constitut ional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ri bonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation and is particularly useful in arthritis treatment. View full drug information Azathioprine (Imuran, Azasan) Azathioprine is an immunosuppressant and a less toxic alternative to cyclophosph amide. It is used as a steroid-sparing agent in nonrenal disease. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decr ease proliferation of immune cells, which results in lower autoimmune activity. View full drug information Mycophenolate (CellCept, Myfortic) Mycophenolate is useful for maintenance in lupus nephritis and other serious lup us cases. This agent inhibits inosine monophosphate dehydrogenase (IMPDH) and su ppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proli feration. It inhibits antibody production. View full drug information Immune globulin intravenous (Hizentra, Gammagard, Octagam, Privigen) This agent is used for immunosuppression in serious SLE flares. It neutralizes c irculating myelin antibodies through anti-idiotypic antibodies. It down-regulate s proinflammatory cytokines, including interferon-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells; and augments suppressor T cells.

It also blocks complement cascade, promotes remyelination, and may increase cere brospinal fluid IgG (10%). Immunomodulators Class Summary These agents restore the potential to minimize self-immunity. View full drug information Belimumab (Benlysta) Belimumab inhibits the biological activity of B-lymphocyte stimulator (BLyS); BL yS is a naturally occurring protein required for survival and for development of B-lymphocyte cells into mature plasma B cells that produce antibodies. In autoi mmune diseases, elevated BLyS levels are thought to contribute to production of autoantibodies. This agent is indicated for active, autoantibody-positive SLE in patients in who m standard therapy, including corticosteroids, antimalarials, immunosuppressives , and nonsteroidal anti-inflammatory drugs, is failing. View full drug information Rituximab (Rituxan) B-cell depletion with rituximab has been used successfully for rheumatoid arthri tis but has shown mixed results for the treatment of SLE. One open study using r ituximab showed excellent results as rescue therapy for patients with active SLE and unresponsive to standard immunosuppressant therapy.[66] However, a placebocontrolled study failed to show an overall significant response.[67] Corticosteroids Class Summary These agents are used predominately for anti-inflammatory activity and as immuno suppressants. Preparations include oral, intravenous, topical, and intraarticula r injections. View full drug information Methylprednisolone (A-Methapred, Medrol, Solu-Medrol, Depo-Medrol) Methylprednisolone is used for acute organ-threatening exacerbations. It decreas es inflammation by suppressing migration of polymorphonuclear leukocytes and rev ersing increased capillary permeability. View full drug information Prednisone Prednisone is an immunosuppressant for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppres sing polymorphonuclear neutrophil activity. It stabilizes lysosomal membranes an d suppresses lymphocytes and antibody production. Low-dose oral prednisone can b e used for milder SLE, but more severe involvement necessitates high doses of or al or intravenous therapy