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

Abstract

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 gene signature in subjects treated with omalizumab (P = 0.11), especially in subjects with a high baseline IFN signature (P = 0.052).Conclusion. Our findings indicate that omalizumab is well tolerated in SLE and is associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess the efficacy of omalizumab in patients with SLE.

What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab duringCOVID‐19 or asymptomatic infections due toSARS‐CoV‐2?

“…29 SLE patients also have serum self-reactive IgE and an increased number of activated basophils in the lymph nodes and spleens that can activate both T and B lymphocytes. [46][47][48] The presence of IgE antibodies against dsDNA, Sm, and SSA was associated with active SLE and hypocomplementemia, suggesting that these autoantibodies may contribute to lupus pathogenesis. [47][48][49][50] Furthermore, IgE autoantibody levels do not correlate with total serum IgE levels and show only a modest correlation with serum IgG autoantibody levels.…”

“…SLE patients also have serum self‐reactive IgE and an increased number of activated basophils in the lymph nodes and spleens that can activate both T and B lymphocytes 46‐48 . The presence of IgE antibodies against dsDNA, Sm, and SSA was associated with active SLE and hypocomplementemia, suggesting that these autoantibodies may contribute to lupus pathogenesis 47‐50 .…”

Systemic lupus erythematosus: year in review 2019

“…The preliminary data from a small RCT published in 2019 indicated that omalizumab, a monoclonal antibody against IgE, was associated with improvement in disease activity in SLE patients, with good tolerance. [ 59 ] It was gratifying that traditional Chinese medicine, artemisinin may be a potential alternative for SLE treatment. A multi-center phase I RCT showed a significantly more favorable response to artemisinin than placebo in mild/moderate SLE patients.…”

IgE in the Pathogenesis of SLE: From Pathogenic Role to Therapeutic Target

“…In a randomized phase Ib clinical trial, realized at the National Institute for Arthritis, Musculoskeletal and Skin diseases (NIAMS, NIH, Bethesda, MD, USA) by Hasni et al [ 70 ], assessing the safety, tolerability and efficacy of Omalizumab in mild and moderate SLE patients, we showed that Omalizumab is well tolerated by SLE patients and is associated with an improvement of the disease, in terms of a reduction in the activity SLEDAI-2K score [ 71 ], and no worsening of the British Isles Lupus Assessment Group index (BILAG 2004) score [ 72 ]. A trend in the reduction in the type I IFN signature was observed in patients, especially those with a high baseline type I IFN signature [ 70 ]. These first very encouraging results, beyond the safety of Omalizumab in SLE, underline the need for larger clinical trials evaluating the efficacy of Omalizumab in SLE and validate the anti-IgE approach as a promising new therapeutic modality in SLE ( Figure 1 ).…”