LOUISVILLE, Kentucky — Patients with chronic spontaneous urticaria (CSU) who experienced a suboptimal response with 12-week omalizumab treatment showed benefit with longer treatment duration or up-dosing of the monoclonal antibody, a study found.
Benefit associated with longer treatment duration or up-dosing was observed in patients with low immunoglobulin E (IgE) and high body mass index (BMI) at time of treatment initiation, suggesting these factors may play a role in treatment decision-making on omalizumab administration.
Lead study author Giselle S. Mosnaim, MD, of the NorthShore University Health System in Evanston, Illinois, presented the study findings at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting 2022 in Louisville, Kentucky.
"CSU is a fluctuating disease with frequent relapses and remissions and so requires frequent re-evaluation in order to make sure you are adjusting therapy accordingly," said Mosnaim.
Omalizumab is recommended by international guidelines as second-line treatment of CSU for 6 months prior to switching to cyclosporin-A. But according to Mosnaim and colleagues, the decision to discontinue omalizumab in clinical practice is often made before the 6-month mark.
"Studies suggest that there are early and late responders to omalizumab, and many patients require multiple doses to receive a response," explained Mosnaim. In particular, Mosnaim added, previous research indicates that patients with lower IgE levels and higher BMI at baseline may experience benefit from longer treatment and/or up-dosing of therapy.
The study by Mosnaim and colleagues was a post hoc analysis of the phase 4 randomized XTEND-CIU study, which included 204 patients aged 12 years and older with symptomatic chronic idiopathic urticaria/CSU (7-day Urticaria Activity Score [UAS7] ≥ 16) despite treatment with H1-antihistamines. Patients in the study had "substantial disease burden" at baseline, according to Mosnaim.
During a 24-week open-label period, all patients received subcutaneous omalizumab 300 mg every 4 weeks. Patients were then randomly assigned to either continue omalizumab or switch to placebo for a follow-on 24-week period.
Early responders during the open-label period were defined as having a UAS7 ≤ 6 at week 12, while late responders were defined as having a UAS7 ≤ 6 at week 24 but not at week 12. The investigators categorized patients by baseline IgE level quartiles as well as by BMI (≥ 30 or < 30).
Nearly 60% (58.82%) of patients were defined as early responders, while late responders comprised 15.9% of the population. The remaining patients had a complete response (UAS7 of 0).
The proportions of late responders who fell into the first quartile of IgE levels (< 32.5 IU/ mL) at screening were 36.67%. For early responders, the proportion in the first quartile was 22.89%. Approximately 53.1% of late responders and 43% of patients who were not late responders had a BMI of 30 or higher at baseline.
Sai R. Nimmagadda, MD, an attending physician in allergy and immunology at the Ann & Robert H. Lurie Children's Hospital of Chicago, told Medscape Medical News that given that CSU often places a higher impact on quality of life than many other skin diseases, there is a need to improve optimal treatment of patients with the condition.
According to Nimmagadda, who wasn't involved in the research, patients with uncontrolled CSU may experience a different dose-response with guideline-recommended therapy. "It's important to understand that some patients will require higher doses of all medications to control their urticaria," he commented.
Nimmagadda added that some patients with lower IgE levels and higher BMI who do not optimally respond to standard dosing of omalizumab "may require higher doses of monthly 450 mg or 600 mg dosing to control CSU," highlighting individualized treatment needs for patients with the disease.
"With the initial FDA approval of omalizumab, the dosing was not based on weight but was based on the diagnosis," Nimmagadda commented. He added that the current limitations with omalizumab treatment in patients with CSU is the fixed dosing schedule without options to adapt the therapy to individual patients.
"In summary, patients who have been poor responders should explore up-dosing at higher levels before discontinuing therapy," Nimmagadda stated.
Anna Wolfson, MD, of Massachusetts General Hospital in Boston, noted that in addition to up-dosing, clinicians should give patients a reasonable timeline for when they can expect to feel better, especially when they are experiencing uncomfortable symptoms. "If we could hasten the time to resolution and get the correct dose more quickly, this would minimize suffering for our patients," she said.
Wolfson commented that if clinicians can use clinical variables such as IgE levels and BMI to identify patients who will need specific protocols, this can further hasten remissions by starting them on the correct doses and regimens. "On the other hand, patients who would not benefit from the longer treatments and up-doses need not take extra medication," she added.
The study was funded by Genentech and Novartis. Mosnaim reported grant funding from Genentech and Novartis. Nimmagadda has disclosed no relevant financial relationships.
American College of Allergy, Asthma, and Immunology (ACAAI) 2022 Annual Scientific Meeting: Abstract #D005. Presented November 12, 2022.
Brandon May is a freelance medical journalist who has written more than 2100 articles for medical publications in the United States and the United Kingdom. Twitter: @brandonmilesmay.
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Cite this: Brandon May. Chronic Spontaneous Urticaria: Longer Treatment and Up-Dosing Benefit Patients With Poor Omalizumab Response - Medscape - Nov 15, 2022.