Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren's Syndrome: Post Hoc Analyses From the EMBODY Trials.

OBJECTIVE: EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell-specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS). METHODS: The efficacy and safety of epratuzumab were compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE patients with and those without a diagnosis of associated SS. British Isles Lupus Assessment Group (BILAG) total score, BILAG-based Combined Lupus Assessment (BICLA) clinical response to treatment, biologic markers (including B cells, IgG, IgM, and IgA), and safety were assessed. RESULTS: A total of 1,584 patients were randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti-SSA positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no diagnosis of associated SS (918 patients were randomized to receive epratuzumab and 457 to receive placebo). For patients with associated SS, but not those without associated SS, a higher proportion of patients receiving epratuzumab achieved a BICLA response and a reduction from baseline in BILAG total score. B cell reduction was faster in patients with associated SS. The sensitivity of B cells to epratuzumab as measured by the mean concentration producing 50% of the maximum B cell count depletion was lower for patients with associated SS (9.5 µg/ml) versus the total EMBODY population (87.1 µg/ml). No difference in the frequency of adverse events in those receiving placebo was reported. CONCLUSION: Patients with SLE and associated SS treated with epratuzumab showed improvement in SLE disease activity, which was associated with bioactivity, such as decreases in B cell number and IgM level.

Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials.

OBJECTIVE: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. RESULTS: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. CONCLUSION: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

Effects of Atorvastatin on some inflammatory parameters in severe primary hypercholesterolemia.

Recent publications have reanimated the point of view that there exist links between atherosclerosis--inflammation and hypercholesterolemia. The aim of our study was to investigate the possible influence of statins on some inflammatory parameters in persons with severe primary hypercholesterolemia (PHC). The effects of the HMG CoA reductase inhibitor--Atorvastatin--on serum lipids, apoproteins, C reactive protein (CRP), soluble Intercellular Adhesion Molecule (sICAM), lipid peroxides, antibodies to oxidized LDL (Ab oxLDL) and homocystein were evaluated in 21 persons (52.9 +/- 8.38 years old) with severe PHC, 12 of these having significant coronary-artery stenosis (diameter stenosis > or = 70%), in at least one major coronary artery branch. Ab oxLDL, sICAM, TBARS, CRP and homocystein were significantly increased (p < 0.05) in patients with coronary-artery stenosis. Following a 4 weeks hypolipemiant free baseline period, all persons were treated with Atorvastatin 40 mg once daily for 8 weeks. Atorvastatin 40 mg resulted in a reduction of LDL-C with 57.8% (baseline 259.6 +/- 71.39 mg%) p < 0.001, total Cholesterol with 44.08% (baseline 343.1 +/- 71.72 mg%) p < 0.001, Apo B with 50.6% (baseline 194.7 +/- 48.71 mg%) p < 0.001, TG with 12.02% (baseline 177.4 +/- 83.63 mg%) and HDL-C was increased with 6.84% (baseline 48.0 +/- 7.86 mg%). In coronary heart disease patients, Atorvastatin reduced homocystein concentrations with 19.41% (baseline 17.7 +/- 11.16 microM/l) (p < 0.01), and CRP with 21.9% (baseline 4.8 +/- 4.19 mg/l) p < 0.01 and TBARS with 52% (baseline 0.87 +/- 0.89 nM/ml) p < 0.001, but did not influence sICAM and Ab oxLDL. Thus atherogenic concentrations of LDL-C have to be closely modulated by minimal changes in LDL oxidative state. The effects of Atorvastatin on inflammatory parameters may crucially contribute to the clinical benefit of statins, independent of cholesterol lowering. Plaque stabilization may be a paradigm for antiinflammatory mechanism of action by this class of drugs.