Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous urticaria - A real-life experience

Abstract

Background Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an "intensified protocol" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype. Methods Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013–2018. Results Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the "intensified protocol" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027). Conclusion r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low "autoallergy"). An "intensified protocol" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.

Combination therapy of omalizumab with house dust mite immunotherapy in chronic spontaneous urticaria associated with sensitization to dust mites-case series

“…There are two endotypes of CSU, Type 1 autoimmune CSU-mediated by IgE antibodies to auto-allergens (auto-allergic) and Type IIb autoimmune CSU-mediated by autoantibodies that target activating mast cell receptors. High total IgE levels (associated with Type I autoimmunity) were related to omalizumab responsive vs. omalizumab resistant CSU phenotype (18% vs. 41%, respectively) while concomitant autoimmunity (which may support Type II autoimmunity) was related to resistant-CSU phenotype (55% vs. 20%, respectively) [5,6]. Dietary elimination, antihistamines, and corticosteroids only provide symptomatic relief.…”

Resistant Chronic Spontaneous Urticaria – A Case Series Narrative Review of Treatment Options

“… 23 – 25 Controversy remains as to whether eosinophil modulation is another mechanism of action of omalizumab in urticaria. 26 – 28 …”

“…[23][24][25] Controversy remains as to whether eosinophil modulation is another mechanism of action of omalizumab in urticaria. [26][27][28] We noted that 4 patients who started dapsone had excellent control of urticaria within 3-10 weeks, though 1 patient with clinical response needed to discontinue due to intolerance. Two other patients developed haematologic toxicity (one also developed hepatotoxicity) within 4-6 weeks.…”

“…She was on metformin 1 g twice daily, levothyroxine 100 μg, ramipril 2.5 mg, fexofenadine 720 mg/ day, hydroxyzine 50 mg, cetirizine 10 mg, prednisolone 10 mg once daily. Her median UAS7 score over past 12 weeks was 22 (range, [16][17][18][19][20][21][22][23][24][25][26][27][28]. She had 2 hospital admissions for hyperglycaemia-requiring sliding scale insulin that was very stressful for her as she was needle phobic.…”

Selective IgE Deficiency Predicts Poor or No Response of Chronic Spontaneous Urticaria to Omalizumab

“…The licensed dose of omalizumab in Europe is 300 mg administered every four weeks. However, augmenting the dose or shortening dose intervals, may provide better symptom control in patients with limited response to the 300 mg dose [6]. It has been shown that low IgE levels, basopenia and eosinopenia prior to initiation of omalizumab therapy are associated with a reduced clinical efficacy [7].…”