In the latest review article in our Clinical Therapeutics series, a 20-year-old woman with SLE presents with disease flares and receives belimumab, a monoclonal antibody that binds to B-cell activating factor, inhibiting B-cell stimulation. Belimumab is considered for patients who do not have a response or have adverse effects with first-line therapies.
• What is the epidemiology of SLE?
Seventy to 90% of affected persons are women, with onset usually in the child-bearing years. The prevalence is 20 to 70 per 100,000 women, and varies by race; the higher prevalence rates are in Latinos, African Americans and Afro-Caribbeans; the lower prevalence rates are in Caucasians and Asians. Overall survival rates also vary by race, with a five-year survival of approximately 95% in whites, 90% in African Americans, and 87% in Hispanics. Men, persons in lower socioeconomic groups, and patients with nephritis have lower survival rates.
• What is the pathophysiology of SLE?
SLE is caused by pathogenic autoantibodies (which generally appear a few years before the first clinical symptoms) and immune complexes that bind to tissue, fix complement, activate inflammatory responses, and mediate tissue damage. In people genetically predisposed to develop autoimmune processes, including SLE, normal immune responses become dysregulated; autoantibody production increases and persists; both innate and adaptive immune systems remain in activated state. Environmental triggers include Epstein-Barr virus infection and exposure to ultraviolet light, estrogen-containing medications, silica dust, and smoking. B cells are central in the pathogenesis of SLE, since they are precursors for plasma cells that secrete antibodies; they also present antigens and secrete proinflammatory cytokines.
Morning Report Questions
Q: What is the mechanism of action of belimumab and what is its clinical indication?
A: The indication for use of belimumab is to induce clinical improvement in seropositive patients with SLE who have active disease despite standard treatment. Determining what constitutes “standard treatment” is a matter of physician judgment. Belimumab is generally given to patients with profiles similar to those in the phase III clinical trials, i.e., persons with enough clinical disease activity to interfere with quality of life, or with unacceptable side effects of the dose of glucocorticoids required for comfort and function, despite current treatment with antimalarial agents (chloroquine and hydroxychloroquine) plus glucocorticoids and one additional immunosuppressant (mycophenolate mofetil, azathioprine, or methotrexate).
Q: What factors make a patient more likely to respond to belimumab, and when is its use contraindicated?
A: Seropositivity to antinuclear antibodies and the presence of anti-double-stranded DNA antibodies identifies likely responders to belimumab. Levels of serum complement are also useful since low levels also identify patients likely to respond, and rising levels are one indication that response is occurring. Contraindications to belimumab therapy include presence of active or chronic infections.