Belimumab (benlysta): a breakthrough therapy for systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that affects approximately 250,000 Americans, with a female-to-male ratio of 10:1.1 SLE occurs predominantly in persons 15 to 64 years of age, and it is more common in women of African-American and Hispanic descent.2 Suspectedcauses of SLE include failure of the immune system’s regulatory mechanisms, immune complex deposition, and direct antibody-mediated cytotoxicity.3 This chronic, multifaceted inflammatory disease consists of a relapsing–remitting course with a broad range of possible clinical and serological manifestations.3,4 Genetics, race, hormones, and the environment are risk factors for the development of SLE. Patients typically present with an array of symptoms, including fatigue, fever, arthralgia, and weight changes.3 As the disease progresses, symptoms may manifest in almost every organ system. The heart, lungs, kidneys, and brain are the organs most affected.5 In addition to the patient’s clinical presentation, laboratory tests, such as a complete blood count (CBC) and a comprehensive metabolic profile, may provide diagnostically useful information when SLE is suspected. In advanced cases, diagnostic imaging, such as radiographs of involved joints, renal ultrasonography, chest radiography, and echocardiography, may be necessary, along with biopsy. Autoantibodies, such as antinuclear antibodies (ANAs), antiphospholipid antibodies, antibodies to double-stranded DNA (dsDNA), and anti-Smith (Sm) antibodies, are routinely assayed.5 Clinicians commonly follow the diagnostic guidelines published by the American College of Rheumatology (ACR); these recommendations were initially developed to standardize entry criteria for clinical trials.4 Various indices are available for determining disease status in patients with SLE.5,6 The most commonly used measure is the SLE Disease Activity Index (SLEDAI). A modification that has been made to SLEDAI over the years is known as the SELENA–SLEDAI. This modified index is a global composite index that includes 24 clinical and laboratory variables; a weighted score is given to each disease symptom.5–7 Petri et al. suggested the following definitions of treatment outcomes based on changes in the SLEDAI index:7 A reduction in the SLEDAI score of more than 3 indicates improvement. A change in the SLEDAI score of 3 indicates persistently active disease. A SLEDAI score of 0 indicates disease remission. Disease activity categories were defined on the basis of SLEDAI scores, as follows: 0 = no disease; 1 to 5 = mild disease activity; 6 to 10 = moderate activity; 11 to 19 = high activity; and 20 = very high activity.7 Therefore, higher scores on the SLEDAI represent increased disease activity.8 By contrast, the British Isles Lupus Assessment Group Index (BILAG) evaluates eight organ systems; each system is weighted by disease severity.6 BILAG consists of letter scores ranging from A to E, with A indicating the most severe stage of disease requiring treatment. Current clinical trials use BILAG scores of A and B. In addition to SLE, three other major types of lupus have been identified:2,4,9 Discoid lupus erythematosus (DLE) affects only the skin, causing thick, red, scaly rashes on the face, neck, and scalp. Drug-induced lupus erythematosus (DIL), a rare form of lupus, is most commonly associated with hydralazine, (e.g., Apresoline, Novartis), which is used to treat hypertension, and procainamide (e.g., Pronestyl, Bristol-Myers Squibb), which is used to treat heart disease. Neonatal lupus er ythematosus (NLE) results when a mother’s antibodies are transferred to her child at birth. The child may develop a rash, anemia, and potentially fatal heart problems. Because SLE can be both debilitating and life-threatening, the disease can significantly affect quality of life. Patients with SLE experience increased fatigue, pain, rash, fever, abdominal discomfort, headache, or dizziness, which can present at the onset of a lupus-associated flare.2 Life expectancy depends on the extent of organ damage at the onset of treatment. An early diagnosis can improve the prognosis. The 20-year survival rate for patients with SLE is 70%.10 If the disease is left untreated, the brain, heart, lungs, kidneys, and other major organs may be compromised.1,2,5 There is no cure for SLE; medical treatment is aimed at reducing symptoms. Lifestyle modifications, such as exercise, smoking cessation, and appropriate nutrition, may also play a part in controlling symptoms. Pharmacological therapy includes drugs that reduce the body’s immune response, such as methotrexate (e.g., Rheumatrex, DAVA); azathioprine (e.g., Azasan, Salix); cyclophosphamide (e.g., Cytoxan, Bristol-Myers Squibb); chlorambucil (Leukeran, GlaxoSmithKline); and cyclosporine (e.g., Neoral, Novartis). Skin rashes are treated with corticosteroid creams, and nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control arthritis and pleurisy. Hydroxychloroquine (e.g., Plaquenil, Sanofi), an antimalarial drug, is also used to treat the dermal and arthritic symptoms of SLE.2,5 In March 2011, the FDA approved belimumab (Benlysta, Human Genome Sciences/GlaxoSmithKline), an innovative therapy for patients with SLE. Benlysta was previously known as Lympho-Stat-B.