Predicting relapse in chronic spontaneous urticaria: A retrospective cohort study evaluating omalizumab withdrawal regimens

Chronic spontaneous urticaria (CSU) affects 0.5%–1% of the population, significantly reducing patients' quality of life, especially in antihistamine-resistant cases.1 Omalizumab, humanized anti-immunoglobulin E antibody, is the only registered therapy for such cases, but its high cost is a concern. Although long-term remission is common2-4 in CSU, the safe discontinuation of omalizumab treatment remains undetermined. Current suggestions are based on expert opinions without supporting studies on long-term remission or relapse predictors.5 In Poland, omalizumab is reimbursed for CSU treatment (300 mg/4 weeks) through the Drug Access Program (DAP) for patients aged 12 or older who have not responded to fourfold dosed antihistamines for at least 4 weeks, as evidenced by Urticaria Activity Score (UAS7) ≥28 and Dermatology Life Quality Index (DLQI) ≥10.6 Omalizumab is administered in 24-week courses, and monitoring visits are conducted after 12 and 24 weeks. If not effective (UAS7 >16 or DLQI ≥10), treatment must be stopped. If it is effective, after 24 weeks therapy must be suspended, and the patient should be observed for an additional 6 months. If there is no relapse during this period, it is considered a long-term remission, and observation ends. However, if urticaria worsens (UAS7 ≥16), treatment is restarted for another 24 weeks (Figure 1). Further details are provided in the Appendix S1. This retrospective, single-center study aimed to determine the proportion of patients who experienced relapse following treatment withdrawal and identify risk factors for relapse. The study findings may be used to suggest appropriate omalizumab withdrawal regimens. Adults receiving omalizumab were evaluated for disease activity and quality of life using UAS7 and DLQI questionnaires. Therapy was considered effective if UAS7 score was ≤16 and DLQI score was <10. Relapses were assessed based on follow-up duration. They were numbered from 1 to 6. One hundred and thirty-nine patients (April 2020–August 2023) received omalizumab treatment, of whom 103 were female (74%). The median time between CSU diagnosis and treatment initiation was 1.9 years (IQR: 0.9–4.4), the median UAS7 score was 35.0 (IQR: 31–38.4) while the median DLQI score was 20.0 (IQR: 16–25). Twenty-nine patients (21%) were diagnosed with Hashimoto's disease. Of the 123 patients observed for a minimum of 24 weeks, 116 (94%) responded to treatment. Of these, 71 experienced improvement within 4–8 weeks (quick responders), whereas the remaining 45 showed improvement at week 12 (slow responders). 30% (n = 30) of the 100 patients analyzed for a relapse experienced long-term remission after the first treatment cycle. Multivariate Cox regression analysis revealed several factors that significantly modified the risk of relapse. These included (1) UAS7 score after 24 weeks as each additional point increased the risk of relapse by 5.4%, (2) a longer time to treatment (TtT), (3) Hashimoto's disease, which reduced the chance of relapse by 50%, and (4) a greater number of relapses. After subsequent treatment cycles, the median time to the next relapse (TnR) gradually decreased and it was statistically significant. TnR was influenced by a longer TtT and higher number of relapses. Among the 160 relapses, almost half (49%) occurred within the initial 6 weeks following the discontinuation of therapy (Figure 2). Conclusions: Long-term remissions are frequently observed in individuals with CSU treated with omalizumab, with approximately 30% of patients achieving them even after just 24 weeks of therapy. Notably, the majority of relapse episodes tend to occur within the initial 6 weeks following the discontinuation of treatment. Factors favoring relapse rates include higher UAS7 scores after 24 weeks of treatment, longer TtT and prior relapses, while Hashimoto's disease is a factor favoring remission. Considering these factors can help determine appropriate treatment duration and withdrawal regimens. Further research is necessary to optimize omalizumab withdrawal and identify additional predictive factors for long-term remissions and relapse rates in CSU patients. In accordance with the local, Polish regulations governing drug access program therapy, patients were required to provide their consent for treatment. Given that the study had a retrospective design, separate patient consent or approval from the Bioethics Committee was not needed. The study was conducted in accordance with all relevant regulations and guidelines. Aleksandra Kucharczyk made substantial contribution to the conception and design of the work, data acquisition, analysis, and interpretation, drafting of the manuscript, and final approval of the manuscript version to be published. Karina Jahnz-Różyk made substantial contributions to interpretation of the data, reviewing the manuscript critically for important intellectual content and for final approval of the version to be published. Katarzyna Marczyk and Barbara Kucharczyk made substantial contributions to the acquisition and interpretation of the data. Robert Plisko is the statistician who conducted the data analysis. Jolana Perkowska and Witold Owczarek made substantial contributions to data collection. All authors provided critical feedback and helped shape the research, analysis, and manuscript. Open access publishing facilitated by The Military Institute of Medicine-National Research Institute. The publication had no funding support. Aleksandra Kucharczyk declares Speaker, Conference with Allergopharma, AstraZeneca, Chiesi, CSL Behring, EMMA, GSK, Novartis, Sanofi, Sun-Farm, and Takeda Polska; Advisory Boards with AbbVie, Chiesi, GSK, Novartis, Pfizer, Sanofi, Takeda Polska, Teva, and Scientific Projects with AstraZeneca and Takeda. Karina Jahnz-Różyk declares Speaker, Conference with Shire, Takeda, Kedrion, CSL Behring, Projects and Advisory Board and personal fees with Shire, Takeda, Abbvie, AstraZeneca, CSL Behring, Allergopharma&CoKG, Baxter Polska, Baxalta International, Boehringer Ingelheim, Chiesi, BristolMyers Squibb, GSK, Novartis, Pfizer, Teva, Lekam, Sanofi-Pasteur, Sanofi-Aventis, Zentiva, Mylan Healthcare Sp. z o.o./Viatris. Other authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. 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