Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti‐IgE Monoclonal Antibody in Systemic Lupus Erythematosus

作者：Sarfaraz Hasni, Sarthak Gupta, Michael A. Davis, Elaine Poncio, Yenealem Temesgen‐Oyelakin, Elizabeth Joyal, Alice Fike, Zerai Manna, Sungyoung Auh, Yinghui Shi, Diana Chan, Philip M. Carlucci, Ann Biehl, Bárbara Dema, Nicolas Charles, James E. Balow, Meryl Waldman, Richard M. Siegel, Mariana J. Kaplan, Juan Rivera · 发表于：Arthritis & Rheumatology · 年份：2018 · DOI：10.1002/art.40828 · 被引用次数：63 · 研究领域：Systemic Lupus Erythematosus Research、Multiple Sclerosis Research Studies、Rheumatoid Arthritis Research and Therapies

OBJECTIVE: Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE. METHODS: Sixteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 and elevated autoreactive IgE antibody levels were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16 weeks of open-label treatment and a 4-week washout period. The SLEDAI-2K score, British Isles Lupus Assessment Group index (BILAG 2004) score, and physician's global assessment of disease activity were recorded at each visit. The type I IFN-induced gene signature was determined using quantitative polymerase chain reaction. RESULTS: Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to those experienced with placebo treatment. SLEDAI-2K scores improved in the omalizumab group compared to the placebo group at week 16 (P = 0.038), as well as during the open-label phase in subjects initially receiving placebo (P = 0.02). No worsening in BILAG scores or the physician's global assessment was detected. There was a trend toward a reduction in IFN ge...