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14th February 2022
The use of lirentelimab in patients with chronic urticaria leads to improved disease control as measured by an increase in urticaria control test scores. This was the conclusion of a study by a team from the Dermatological Allergology, Allergie-Centrum-Charite, Department of Dermatology and Allergy, University of Berlin, Berlin, Germany.
Urticaria is a superficial swelling of the skin leading to a red, raised and intensely pruritic rash. When an urticaria involves recurrent episodes occurring at least twice a week for 6 weeks, it is termed ‘chronic urticaria’. The global prevalence of chronic urticaria varies, with a 2020 systematic review identifying a higher point prevalence in Asian (1.4%) compared to European (0.5%) and Northern American (0.1%) studies. The primary effector cell in chronic urticaria is the mast cell and these are located in the upper dermis and increased numbers of mast cells are found in both lesional and non-lesional skin urticarial skin. The aim of treatment in chronic urticaria is achievement of complete control of symptoms and oral non-sedating antihistamines are the first-line recommendation. However, at licensed doses, anti-histamines provide effective symptomatic relief in less than 50% of patients. Although guideline-recommended up-dosing up to fourfold increases symptom control for some patients, many derive little benefit from antihistamines, highlighting the need for alternative therapies. Other effective treatments for chronic urticaria include the monoclonal antibody, omalizumab, which has be shown to be effective for those resistant to antihistamine therapy.
Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) are cell surface proteins found predominantly on cells of the immune system. Siglec-8 is uniquely expressed by human eosinophils and mast cells and binding of monoclonal antibodies such as lirentelimab to Siglec-8 has been shown to inhibit IgE-mediated mast cell activation.
Lirentelimab has been shown to prevent passive systemic anaphylaxis through mast cell inhibition and given this finding, for the present, open-label, Phase II study, the German researchers sought to evaluate the impact of lirentelimab on symptom control in patients with chronic urticaria.
They recruited individuals with a diagnosis of chronic urticaria for 3 or more months that was uncontrolled based on an urticaria control test score (UCT) of less than 12. Patients received up to six intravenous infusion doses of lirentelimab, ranging from an initial 0.3 mg/kg up to 3 mg/kg if tolerated. The primary efficacy outcome was the change in UCT scores from baseline to week 22 and a secondary outcome the proportion of those achieving a complete response (CR). Enrolled patients were categorised based on their chronic urticaria subtype as omalizumab-naïve, omalizumab-refractory, chronic spontaneous urticaria and chronic inducible urticaria.
Lirentelimab and UCT scores
A total of 45 patients with a median age of 42 years (74% female) were enrolled in the study. Patients in each of the subgroups experienced an improvement in UCT scores. Mean increases from baseline were 11.1 for omalizumab-naive, 4.8 for omalizumab-refractory, 6.5 for chronic spontaneous urticaria and 3.4 for chronic inducible urticaria.
For the secondary outcome, 92% of omalizumab-naive, 36% of omalizumab-refractory and 82% of those with chronic spontaneous urticaria, achieved a complete response at week 22.
The authors concluded that lirentelimab showed efficacy across a range of chronic urticaria subtypes including those refractory to omalizumab.
Altrichter S et al. An open-label, proof-of-concept study of lirentelimab for antihistamine-resistant chronic spontaneous and inducible urticaria J Allergy Clin Immunol 2022
11th October 2021
Chronic urticaria (CU) is a recurrent skin condition characterised by hives, angioedema or both. The prevalence appears to vary across the world, with one 2020 review of studies indicating a prevalence of 1.4% in Asian, 0.5% in European and 0.1% in North American studies. The condition creates a huge burden on patients, markedly interfering with sleep, daily activities and overall quality of life. Interestingly, one study found that a quarter of patients with CU experienced sleep-related breathing disorders and in a small study of 31 patients with chronic idiopathic urticaria, 13 were diagnosed with obstructive sleep apnoea (OSA), one of whom had severe OSA.
Given that a proportion of patients with chronic urticaria have sleep-related breathing problems and even OSA, the precise nature of this relationship and whether CU and OSA are causally related remains uncertain. This led a team from the Department of Immunology and Pulmonary Medicine, San Jorge, Ecuador, to undertake a cross-sectional study among patients with CU to determine the frequency of OSA risk factors. Included patients were 18 years and over with a diagnosis of CU and all were screened using the STOP-Bang questionnaire, which is a highly sensitive screening tool for OSA. The “STOP” part of the questionnaire enquires about snoring, tiredness during the day, observed apnoea and high blood pressure, whereas the “Bang” part screens patients for a high body mass index (BMI > 35), age (> 50), neck circumference (> 40 cm) and male gender. Using STOP-Bang questionnaire, patients were categorised as low risk (scores 0 -2), intermediate risk (scores 3 – 4) and high ( scores 5 – 8). Patients deemed at intermediate risk were reclassified as high risk if they had two positive responses from the STOP part and were male and with a BMI > 35. In addition, patients completed the Urticaria Activity Score summed over 7 days (UAS7) which assesses itch severity and hive count. The USA7 categorises patients in terms of disease severity, with higher scores indicating more severe disease. Further questionnaires completed included a chronic urticaria quality of life questionnaire and the urticaria control test (UCT), which defines patients as being either poorly controlled or well-controlled.
A total of 171 patients with a mean age of 41.9 years (68.4% female) were included. The mean STOP-Bang score was 2.5 with 24% and 21% of patients classed as being at intermediate and high risk of OSA, respectively. There was a statistically significant association (Cramer’s V = 0.263, p < 0.001) between the UAS7 categories and the STOP-Bang risk categories. In fact, more than half of the subjects within the “moderate-severe” category (based on the UAS7 score) had an intermediate or high risk for moderate-to-severe OSA. There was also a significant association between UCT categories and STOP-Bang risk categories, such that 82.4% of patients with controlled urticaria had a low risk of OSA.
The authors concluded that their data suggested that a considerable proportion of patients with chronic urticaria were at intermediate to high risk for OSA, based on the STOP-Bang questionnaire. They added how further support for this conclusion came from the associations between higher disease activity and poor disease control. They called for more studies to determine the exact link between the two conditions.
Cherrez-Ojeda I et al. Chronic urticaria and obstructive sleep apnea: is there a significant association? World Allergy Org J 2021