In patients with mild to moderate systemic lupus erythematosus (SLE), omalizumab, an immunoglobulin E (IgE)-binding monoclonal antibody that limits type I interferon production, was safe and well-tolerated compared with placebo, according to findings published in Arthritis & Rheumatology.
One suspected mechanism of SLE pathogenesis involves autoreactivity of IgE antibodies against double-stranded DNA and other autoantigens, with IgE immune complexes implicated in interferon production that helps sustain and drive SLE autoimmunity. Investigators sought to determine whether depletion of IgE autoantibodies would help improve disease activity in the first trial, using omalizumab as add-on therapy for SLE.
A 3-phase, double-blind, placebo-controlled, randomized phase 1b clinical trial (ClincalTrials.gov identifier: NCT01716312) enrolled 16 adult patients with SLE with elevated IgE autoantibodies and a SLE Disease Activity Index 2000 (SLEDAI 2K) score >4. The participants were randomly assigned to receive omalizumab (n=10) or placebo (n=6); however, one participant in the placebo group withdrew after randomization. Participants had similar demographics, except for a significantly longer SLE duration in the treatment group (P =.02). At baseline, all participants were taking hydroxychloroquine, and 12 were also receiving prednisone.
For the first 16 weeks, the treatment group received omalizumab as a 600-mg loading dose with 300-mg boosters every 4 weeks. The second 16-week period was an open-label phase in which all individuals were prescribed omalizumab according to the phase 1 protocol. The third phase comprised a 4-week washout period in which all participants discontinued omalizumab.
Clinical end points included adverse events and disease activity measures such as the British Isles Lupus Assessment Group (BILAG) 2004 index and Physician Global Assessment (PGA) scores, in addition to SLEDAI 2K scores. Researchers also evaluated changes in the type I interferon gene signature, using quantitative polymerase chain reaction. Linear mixed modeling was used to estimate least squared means to summarize significant treatment differences.
Study adverse events were generally mild in both groups, without allergic reactions, and omalizumab displayed excellent tolerability overall, with only 3 serious adverse events reported. In the first phase, at 16 weeks, the omalizumab group saw significant improvements in SLEDAI 2K scores compared with placebo (P =.038). At 32 weeks, patients receiving placebo also had significantly improved scores after being placed on omalizumab (P =.020). During the washout phase, SLEDAI 2K scores trended worse by 36 weeks (P =.54).
During these same periods, there was no worsening of either BILAG or PGA scores, nor any deterioration in patient-reported outcomes. There was a nonsignificant trend observed toward a reduced interferon gene signature in those treated with omalizumab (P =.11), particularly in patients with higher baseline signatures (P =.052).
Study limitations included a small sample size and a lack of elucidation of the omalizumab mechanism of action.
“Omalizumab is well tolerated in SLE and associated with improvement in disease activity,” the authors concluded, who recommended that future research involve larger cohorts with increased disease activity at baseline in studies that are sufficiently powered to evaluate efficacy.
Hasni S, Gupta S, Davis M, et al. Safety and tolerability of omalizumab, a randomized clinical trial of humanized anti-IgE monoclonal antibody in systemic lupus erythematosus (STOP LUPUS) [published online December 29, 2018]. Arthritis Rheumatol. doi: 10.1002/art.40828