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Multicenter Study
. 2024 Sep 1;160(9):927-935.
doi: 10.1001/jamadermatol.2024.2056.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation

Reineke Soegiharto  1 , Mehran Alizadeh Aghdam  1 , Jennifer Astrup Sørensen  2 , Esmee van Lindonk  3 , Ferhan Bulut Demir  4 , Nasser Mohammad Porras  5 , Yoshimi Matsuo  6 , Lea Kiefer  7   8 , André C Knulst  1 , Marcus Maurer  7   8 , Carla Ritchie  9 , Michael Rudenko  10 , Emek Kocatürk  7   11 , Roberta F J Criado  12 , Stamatis Gregoriou  13 , Tatjana Bobylev  14 , Andreas Kleinheinz  14 , Shunsuke Takahagi  6 , Michihiro Hide  6   15 , Ana M Giménez-Arnau  5 , Andaç Salman  4   16 , Rabia O Kara  17 , Bahar Sevimli Dikicier  17 , Martijn B A van Doorn  3   18 , Simon F Thomsen  2 , Juul M P A van den Reek  19 , Heike Röckmann  1
Affiliations
Multicenter Study

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation

Reineke Soegiharto et al. JAMA Dermatol. .

Erratum in

  • Error in Figure.
    [No authors listed] [No authors listed] JAMA Dermatol. 2024 Nov 1;160(11):1257. doi: 10.1001/jamadermatol.2024.4573. JAMA Dermatol. 2024. PMID: 39412760 Free PMC article. No abstract available.

Abstract

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation.

Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population.

Design, setting, and participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab.

Main outcomes and measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation.

Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness.

Conclusion and relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Alizadeh Aghdam reported personal fees from Novartis outside the submitted work. Dr Knulst reported grants from Novartis outside the submitted work. Dr Maurer reported grants and personal fees from Allakos, Amgen, Celldex, Evommune, GSK, Lilly, Mitsubishi Tanabe Pharma, Noucor, Novartis, Sanofi/Regeneron, Teva, Third HarmonicBio, and Yuhan Corporation; personal fees from Alvotech, Aquestive, Aralez, Bayer, Celltrion, Ipsen, Menarini, Orion Biotechnology, Resonance Medicine, Septerna, Trial Form Support Int, ValenzaBio, and Zurabio; grants from AstraZeneca, Kyowa Kirin, Leo Pharma, and Moxie during the conduct of the study; and being a speaker and/or advisor for and/or receiving research funding from Astria, BioCryst, Centogene, CSL Behring, Ipsen, Kalvista, Pharvaris, and Takeda. Dr Criado reported personal fees from Novartis and Sanofi and nonfinancial support from Pfizer outside the submitted work. Dr Kleinheinz reported personal fees from Novartis outside the submitted work. Dr Takahagi reported grants from Takeda, Mitsubishi-Tanabe, Maruho, Lilly, Sanofi, and Taiho Pharma; personal fees from Mitsubishi-Tanabe, CSL Behring, Kaken, Maruho, Takeda, and AbbVie outside the submitted work. Dr Hide reported personal fees from Amgen, nonfinancial support from Centogene, personal fees from CSL Behring, Eisai, GI-Innovation, GSK, Kaken, Kyorin, Kyowa Kirin, Mitsubishi-Tanabe, Novartis, Sanofi/Regeneron, Taiho, Teikoku, UCB, and Uriach outside the submitted work. Dr Giménez-Arnau reported grants from Novartis and personal fees from Novartis during the conduct of the study; grants from Noucor, Escient Pharmaceuticals, Leo Pharma, Instituto Carlos III- FEDER, personal fees from Noucor, GSK, Sanofi-Regeneron, Amgen, Sanofi -Regeneron, Thermo-Fisher, Mitsubishi Tanabe, Servier, Menarini Education, Almirall, and Avene outside the submitted work. Dr Salman reported personal fees from AbbVie, Bayer, Menarini, Pfizer, Sanofi outside the submitted work. Dr Kara reported personal fees from Novartis, AbbVie, and grants from Sakarya University Faculty of Medicine Novartis outside the submitted work. Dr van Doorn reported support from Novartis, AbbVie, Pfizer, LEO Pharma, Sanofi, Lilly, Janssen, UCB, BMS, Celgene, and Third Harmonic outside the submitted work. Dr Thomsen reported grants from Novartis, UCB, and LEO Pharma outside the submitted work. Dr van den Reek reported personal fees from AbbVie, Janssen BMS, Leo Pharma, Novartis, Eli Lilly, and support from Almirall, Celgene, and Pfizer outside the submitted work. Dr Röckmann reported financial support from Novartis, Third Harmonic, Pharming, Sanofi outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Drug Survival of Omalizumab in Chronic Urticaria Patients
A, Drug survival rates for overall drug survival (total) and the various reasons for discontinuation, including well-controlled disease, adverse effects, and ineffectiveness. B, The overall drug survival of omalizumab differentiated per subcategory of chronic urticaria. The survival curves are cut off at 7 years as the survival rates remain unchanged thereafter. CSU indicates chronic spontaneous urticaria; CIindU, chronic inducible urticaria.
Figure 2.
Figure 2.. Multivariate Analysis of Determinants of Time to Discontinuation Due to Well-Controlled Disease, Ineffectiveness, and Adverse Effects
All variables (patient and protocol aspects) with P ≤ .20 in the univariate Cox regression analysis were included in the multivariate Cox regression analysis. The multivariate Cox regression analyses were all performed on an imputed dataset. The analysis for determinants of adverse effects was performed only with patient characteristic variables as there were too few events (n = 44) to include protocol aspects.
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References

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