Recent Developments in the Treatment of Systemic Lupus Erythematosus

Carolina Marín Huertas, Fernando Salvador, David Isenberg
European Musculoskeletal Review, 2012;7(1):14-7
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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disorder, characterised by pathogenic antibodies produced by hyper-reactive B cells recognising self-antigens, which cause organ damage via immune complex formation, complement activation and direct effects on cells. It can be a life-threatening disease when major organs, such as the kidneys, are affected. Lupus is approximately 10 times more common in women than in men. The majority of lupus patients will develop their disease between the ages of 15 and 50. If not treated promptly, a significant proportion of patients, especially those with more aggressive disease, accumulate irreversible damage. Accelerated atherosclerosis and infections represent a major challenge in the management of the disease. Conventional drug treatment options range from non-steroidal anti-inflammatory drugs to immunosuppressive therapies. Understanding the disease pathogenesis has led to the use of targeted therapies, notably biological agents. This article will focus on the traditional immunosuppressive therapies used in the treatment of SLE and the biological therapies recently developed.
Keywords
Systemic lupus erythematosus, lupus nephritis, traditional treatment, biological agents, complications
Disclosure Carolina Marín Huertas is funded by the Spanish Society of Rheumatology. The remaining authors have no conflicts of interest to declare.
Received: January 04, 2012 Accepted January 24, 2012
Correspondence: David Isenberg, Room 424, The Rayne building, University College London, 5 University Street, London WC1E 6JF, UK. E: d.isenberg@ucl.ac.uk
Traditional Treatment Options

Patients with mild systemic lupus erythematosus (SLE) can use paracetamol and non-steroidal anti-inflammatory drugs (though gastrointestinal and renal monitoring may be required) for symptoms of arthralgia, mild serositis and fever. In addition, patients must avoid bright sunlight. Hydroxychloroquine, the antimalarial drug of choice, is used in skin involvement, arthritis and general malaise. Steroids (which may cause osteoporosis, high blood pressure, diabetes mellitus, hirsutism or risk of infection) are required when non-steroidal anti-inflammatory drugs and antimalarials are insufficient to relieve the patient´s symptoms. They may be prescribed at higher dosages (more than 20 mg/day) when SLE causes more severe effects. Methotrexate can be useful for inflammatory arthritis, but its possible side effects on the marrow, liver and lungs must be monitored.

Patients with severe SLE, such as significant haematological manifestations or renal or central nervous system (CNS) involvement, require immunosuppressive therapy to induce and maintain remission. Examples include drugs such as azathioprine (AZA) (which rarely causes bone marrow suppression and gastric intolerance), cyclophosphamide (CY) (infection, ovarian failure, haemorrhagic cystitis) and mycophenolate mofetil (MMF) (haematological and gastrointestinal toxicity).

The treatment of lupus nephritis (LN) requires more attention, as failure to control kidney inflammation leads to renal failure.1 Disease activity in LN has been assessed in a trial (Aspreva lupus management study [ALMS]) involving 370 patients, comparing MMF versus CY as induction treatment. Patients with active LN (renal biopsy class III, IV or V) were recruited for the study and treated with MMF (target dosage 3 g/day) or intravenous (iv) CY (0.5–1.0 g/m2/month), plus tapered prednisone for 24 weeks. After six months, both drugs achieved full remission in 50–60 % of the patients. In addition to the efficacy of both treatments on the renal system, this study showed that remission could also be induced in other systems. There was no clear difference in efficacy between MMF and iv CY in ameliorating the renal and non-renal manifestations. MMF is, therefore, a suitable alternative to CY for the treatment of patients with biopsy-proven LN.2,3 However, it should be noted that more Black and Hispanic patients responded to MMF than to CY.

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