Anna, a 35-year-old lawyer, reports having had hives on most days of the week during the past year. The hives are not associated with any type of exposure. She has tried H1-antihistamines, taking up to four times the recommended daily dose on advice from her primary care physician, but continues to have flares. Because of the itching, Anna is not sleeping well and is unable to concentrate at work. At the clinic, she is diagnosed with chronic spontaneous urticaria (CSU) and wants to know more about CSU and what treatment options are available.
CSU is defined by the presence of hives, angioedema, or both for 6 weeks or more in the absence of identifiable triggers. It can severely affect quality of life and take years to resolve. The current first-line treatment for CSU is escalating doses of antihistamines. Omalizumab, an anti-IgE monoclonal antibody, can be added as a second-line agent for CSU that is not controlled with antihistamines, although only some patients experience complete resolution. Ligelizumab is a similar monoclonal antibody that binds to IgE with greater affinity than omalizumab and may be a promising therapeutic agent.
In a phase 2 dose-finding study recently published in NEJM, investigators reported that a higher percentage of patients with CSU who were randomized to ligelizumab therapy had complete remission, compared with omalizumab or placebo. An editorialist calls for more clinical experience and larger trials before ligelizumab is considered the initial second-line therapy for patients like Anna.
The following NEJM Journal Watch summary explains the study and results in more detail.
New Therapy for Chronic Urticaria
David J. Amrol, MD reviewing Maurer M et al. N Engl J Med 2019 Oct 3
Ligelizumab, which is not yet FDA-approved, might be more effective than omalizumab.
Chronic spontaneous urticaria (CSU) is defined as presence of hives (and often angioedema) on most days of the week for longer than 6 weeks with no apparent cause. Although the pathogenesis is unclear, as many as half of patients with CSU have autoantibodies directed against immunoglobulin E (IgE) receptors on mast cells. In an industry-sponsored study, researchers compared ligelizumab, a new anti-IgE monoclonal antibody that is not yet FDA-approved, to currently approved omalizumab (Xolair) in 382 adult patients whose CSU was uncontrolled with antihistamines.
Patients were randomized to monthly subcutaneous injections of ligelizumab, omalizumab, or placebo. All patients were treated with H1-antihistamines, and many used H2-antihistamines and leukotriene-receptor blockers as well. At 12 weeks, about half of patients who were treated with ligelizumab had complete control of their hives, compared with 26% of patients who received omalizumab and no patients who received placebo.
Comment: CSU is not life threatening, but it has an enormous effect on patients' quality of life and typically takes years to resolve. Only about half of patients respond to high-dose antihistamines (I typically prescribe 20-mg cetirizine, twice daily), and prior to omalizumab's approval, many antihistamine-nonresponsive patients ended up receiving long-term steroids. Ligelizumab might be even more effective but also will likely be even more expensive than omalizumab, which is currently priced around US$1,000 per vial before rebates (most patients use 2 vials monthly). The omalizumab response in this trial was lower than that seen in previous studies (and in my practice), possibly because enrolled patients had more-severe disease.
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Connie Zhong is an MD candidate at Harvard Medical School with interests in medical education, community-based interventions, and clinical research. She graduated from Harvard College with a BA degree in neurobiology and the University of Oxford with a master's degree in social policy and intervention. She enjoys cooking/baking and running along the Charles River Esplanade.
Ken is a 2019-2020 NEJM Editorial Fellow and a paediatrician working in the National Health Service of the United Kingdom. He graduated from Imperial College School of Medicine and is training in general paediatrics in London.