EDITORIAL

The heterogeneity of lupus poses a signifi cant challenge for clinical trial design. The pleomorphic nature of the clinical manifestations, the severity of the patient population, the ethnicity infl uence on disease activity, and the diffi culties in attempts to perform trials with larger sample size are leading to diffi culties and failure in achieving statisti-cal signifi cance for new therapies. Many of the trials exclude patients with renal and central nervous system manifestations in an attempt to detect effi cacy in less severe disease states. On this editorial we make some general comments on the trials recently performed. The EXPLORER trial enrolled 257 patients with moder-ately to severely active extrarenal lupus. Patients were ran-domized to receive rituximab plus prednisone or placebo plus prednisone and were followed for 78 weeks. The study failed to achieve primary and secondary endpoints. The LUNAR study enrolled patients with biopsy proven active lupus nephritis. The overall design was similar to the EXPLORER, and the success was defi ned by renal response at one year. The drug failed primary and secondary endpoints. "The effi cacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythe-matosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial" assessed the effect of abatacept in the incidence of fl are rates on a background of oral glucocorticoids. Patients included in the study had to have had a lupus fl are within 14 days before entering the trial and on a stable dose of prednisone less than 30 mg/day. One hundred and seventy fi ve patients received treatment: 118 patients were randomized to receive abatacept and 57 to receive placebo. The study did not show differences in fl are rates of BILAG A and B events.1 Belimumab is a human monoclonal antibody that inhibits the B-lymphocyte stimulator (BLyS) and proved more effec-tive than placebo in treating people with serologically active SLE. Efficacy analyses included the SELENA-SLEDAI, Lupus clinical trials: medication failure or failure in study desig