Belimumab. No tangible efficacy but a risk of immunosuppression.

Systemic lupus erythematosus is a chronic inflammatory autoimmune disease with variable clinical manifestations, mainly affecting women between the ages of 16 and 55 years. It can be life-threatening, especially when renal or neurological involvement occurs. Belimumab (Benlysta", Glaxo-SmithKline) is an immunosuppressant monoclonal antibody that inhibits B cell differentiation into antibody-producing plasma cells. Belimumab is authorised in the European Union for the treatment of adults with autoantibody-positive systemic lupus erythematosus when the disease remains highly active despite "standard" therapy, usually comprising a corticosteroid or another immunosuppressant. In this setting, two double-blind randomised placebo-controlled trials compared two doses of belimumab (1 or 10 mg/kg), given every 2 weeks and then every 4 weeks, in addition to "standard" treatment, in a total of 1684 adult patients. Patients with severe renal or central nervous system involvement were excluded. After 52 weeks the proportion of patients who "responded" to add-on therapy was about 10% higher with belimumab (10 mg/kg) than with placebo, a statistically significant difference. However, this advantage did not persist in one trial that was continued until 76 weeks. Belimumab had no statistically significant benefit in terms of corticosteroid use, time to exacerbations, or quality of life. In a combined analysis of the two trials, the difference in the response rate was greater in the prospectively defined subgroup of patients with "highly active" disease (63.2% with belimumab 10 mg/kg versus 44.3% with placebo; p<0.0001). Adverse reactions can occur during belimumab infusion, including severe and sometimes late-onset hypersensitivity reactions. The risk of infections (particularly opportunistic infections) and cancer is poorly documented. Belimumab also carries a risk of additional immunosuppression when used in combination with other immunosuppressive drugs. In early 2013, given the lack of any proven benefit and the uncertainties surrounding its adverse effects, belimumab add-on therapy simply complicates the treatment of systemic lupus erythematosus and should not be used.