Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER)

Abstract

The EXPLORER study was designed to assess the response to rituximab versus placebo in patients with moderate to severe extrarenal systemic lupus erythematosus (SLE) receiving background immunosuppression. The definition of response required reduced clinical activity without subsequent flares over 52 weeks, and the study did not meet its efficacy endpoint. The current exploratory analysis assessed flare rates in patients who achieved initial low disease activity response (British Isles Lupus Assessment Group [BILAG] C or better in all organs) during the study. Exploratory reanalysis of data from the EXPLORER trial was conducted, considering alternative definitions for flare. No difference was found between rituximab and placebo in preventing or delaying moderate to severe flares. However, when severe (BILAG A) flares alone were examined, rituximab reduced the risk of a subsequent first A flare (hazard ratio ¼ 0.61; p ¼ 0.052) and lowered mean AE SD annualized A flare rates (0.86 AE 1.47 vs. 1.41 AE 2.14; p ¼ 0.038). Eighty-four (49.7%) rituximab-treated patients achieved low disease activity without subsequent A flares versus 31 (35.2%) placebo-treated patients (p ¼ 0.027). Prednisone rescue for A flares was similar in rituximab-(24%) and placebo-treated (14%) patients (p ¼ 0.204). This post hoc analysis evaluates the hypothesis that assessment of BILAG A flares may distinguish potential treatment effects with greater sensitivity than assessment of BILAG B flares. Lupus (2011) 20, 709-716.

Warm Autoimmune Hemolytic Anemia: Clinical Profile and Management

“…In an Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER), the double-blind trial demonstrated that rituximab decreased B cells and anti-dsDNA autoantibody with increased C3 and C4 levels [65]. In a retrospective study of 53 patients with refractory AIHA administered rituximab in Belgium, the overall response rate was 79% with 47% CR and 32% of PR [56].…”

Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis

“…Tables 1 and 2 show a summary of included studies. We found 2 RCTs (Furie et al, 2009;Merrill et al, 2011) and 19 observational studies (Leandro et al, 2002;Leandro et al, 2005;Vigna-Perez et al, 2006;Gunnarsson et al, 2007;Tokunaga et al, 2007;Sutter et al, 2008;Tamimoto et al, 2008;Melander et al, 2009;Pepper et al, 2009;Catapano et al, 2010;Lateef et al, 2010;Ramos-Casals et al, 2010;Terrier et al, 2010;Pinto et al, 2011;Roccatello, 2011;Tony et al, 2011;Turner-Stokes et al, 2011;Vital et al, 2011;Arce-Salinas et al, 2012).…”

“…We included the RCTs 'Explorer' (Merrill et al, 2011) and 'Lunar' (Furie et al, 2009) and summarized the characteristics of the two RCTs (Table 2). …”

Targeted Therapy and Infections in Rheumatic Diseases

“…Курс те-рапии РТМ не был завершен в результате плохой переноси-мости у 7 пациентов с высокой активностью СКВ, из них у 5 больных были сопутствующие инфекционные осложне-ния (у 4 -пневмонии) [27]. В то же время в данной работе частота тяжелых КИ была ниже, чем в других исследовани-ях РТМ у больных СКВ -EXPLORER (9,5%) [28] и LUNAR (16,4%) [29].…”