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Omalizumab (Xolair), the monoclonal antibody targeting immunoglobulin E (IgE), showed some possible utility as an add-on treatment for systemic lupus erythematosus (SLE) in a phase Ib study conducted by the National Institutes of Health.

At week 16, patients who had received omalizumab plus background therapy had statistically significant improvements on the SLE Disease Activity Index (SLEDAI), although the reduction was only an average of two points, which might not be considered clinically meaningful, according to Sarfaraz Hasni, MD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and colleagues.

The drug was well tolerated, with no systemic or local allergic reactions during 36 weeks of follow-up, the researchers reported online in .

"Omalizumab is a humanized IgG1 monoclonal antibody against human IgE that blocks the ability of IgE to bind FcεRI," the investigators explained. The resulting depletion of IgE is thought to reduce the level of autoantibodies and to block the production of type I interferon. It has been approved by the FDA for the treatment of chronic idiopathic urticaria and asthma.

It was previously thought that most of the pathogenic autoantibodies that typify SLE belonged to the IgG subclass, but the NIH researchers the presence of IgE antibodies against double-stranded (ds) DNA in a murine model.

Therefore, to explore the possibility that omalizumab might be useful in SLE, the investigators enrolled 16 patients, randomizing them to receive subcutaneous omalizumab or placebo for 16 weeks, followed by all patients receiving the active treatment for an additional 16 weeks. Patients were then followed off the drug for another month.

Omalizumab was given as a 600 mg loading dose and then 300 mg every 4 weeks.

Participants were required to have elevated levels of IgE-anti-dsDNA, anti-Sm, or anti-SSA autoantibodies, and moderate disease as defined by a SLEDAI of 4 to 14. Stable background immunosuppressives were permitted; all patients were taking hydroxychloroquine, and most also were on prednisone with an average daily dose of 7 mg.

Ten of the patients were randomized to have active treatment and six to placebo.

Among those in the omalizumab group for the entire study, the improvement in SLEDAI was maintained through week 32, and there was a trend toward worsening during the 4 weeks after treatment cessation. For those who were initially on placebo but switched to the active treatment after the first 16 weeks, improvements in SLEDAI were seen during the subsequent 16 weeks. Most improvements were in arthritis, rash, and serologic findings.

Three patients achieved a composite SLE Responder Index score of 4, two initially randomized to omalizumab by week 16 and one who switched from placebo by week 32. This low level of response may reflect the small sample size and participants' relatively mild disease, according to the researchers.

There also was a trend toward improvement in patients' interferon signature, particularly among those with a high signature at baseline. "This suggests that omalizumab may modulate type I interferon pathways by blocking self-reactive IgE," Hasni and co-authors noted.

During the study and follow-up, a total of 52 adverse events were reported, most of which were mild or moderate.

In the first 16 weeks, there were nine adverse events in the omalizumab group and 12 in the placebo group. No pattern of organ involvement was identified for adverse events.

Three serious adverse events were reported. One was a patient on placebo who had bronchitis and developed chest pain, the second was a patient on omalizumab from West Africa who had no evidence of immunity to chicken pox and developed varicella infection after exposure to the disease, and the third had a pulmonary embolism shortly after the switch from placebo to omalizumab.

"A potential advantage of omalizumab in SLE is a side effect profile different from immunosuppressive drugs and a convenient once-a-month subcutaneous administration schedule," Hasni and colleagues wrote.

In a of this agent among patients with asthma, a potential risk for cardiovascular and cerebrovascular events was observed, which raises the question of whether the occurrence of a pulmonary embolism in one patient after receiving omalizumab could have resulted from the treatment or the increased background thromboembolic risk among patients with SLE, the researchers said. They added that future studies should address this question through measurements of vascular risk markers and evaluation of vascular function.

"Overall, this is the first trial to test the safety and potential efficacy of blocking IgE autoantibodies as a novel non-immunosuppressive agent in treatment of SLE," Hasni and co-authors concluded. Additional larger studies will be needed to more fully evaluate the efficacy and safety of this agent.

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