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

Ramit Maoz-Segal; Tanya Levy; Soad Haj-Yahia; Irena Offengenden; Mona Iancovich-Kidon; Nancy Agmon-Levin

doi:10.1016/j.waojou.2020.100448

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

World Allergy Organ J. 2020 Aug 4;13(8):100448. doi: 10.1016/j.waojou.2020.100448. eCollection 2020 Aug.

Authors

Ramit Maoz-Segal¹, Tanya Levy¹, Soad Haj-Yahia^{1

2}, Irena Offengenden¹, Mona Iancovich-Kidon^{1

2}, Nancy Agmon-Levin^{1

2}

Affiliations

¹ Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.
² Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, Israel.

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.

Keywords: ANA, anti-nuclear antibodies; Autoallergy; Autoimmunity; CSU phenotypes; CSU, chronic spontaneous urticaria; Cyclosporine; FceR1, high-affinity receptor for Immunoglobulin E; IL-24, interleukin 24; IgE, immunoglobulin E; Omalizumab; Or-CSU, Omalizumab responsive CSU; Resistant CSU; r-CSU, resistant chronic spontaneous urticarial.