Answer:
Omalizumab is effective for spontaneous urticaria, though complete resolution, or an urticaria activity score of zero, occurs only in approximately 30% of treated subjects in clinical trials, with approximately 30% having significant, persistent symptoms (1). Thus, complete resolution is not generally my expectation with omalizumab therapy, though the patient and I are grateful when that occurs. Higher doses of omalizumab, up to 450 mg every 2 weeks (unapproved dosing), increases clinical response (1,8). Individuals with autoimmune features have a delayed response, but 7 doses should be a sufficient time to realize the likely maximum response (2). IgE concentration prior to omalizumab predicts urticaria response (3,4). However, after initiating therapy with omalizumab, the total IgE will be increased due to the prolonged half-life of the IgE-omalizumab complexes, reducing the utility of total IgE on therapy (5). However, a low level, for example less than 50-75 kU/L, might suggest that the omalizumab will be less effective.
Dupilumab is under investigation in clinical trials for urticaria and may receive FDA approval in the near future (6,7). Current practice parameters suggest that calcineurin inhibitors, particularly cyclosporin, should be considered if omalizumab is not adequately effective (8). Cyclosporin does not have an FDA indication for urticaria and has side effect concerns, including hypertension and renal insufficiency, though in my experience this is seldom a problem with the dose utilized for urticaria.
In summary, my recommendation would be to measure a total IgE while receiving omalizumab. If this is greater than 90-100 kU/L, I would increase the dose of omalizumab to 300-450 mg every 2 weeks IF approval or availability (samples for example) is an option. If no improvement after 2-3 months, I would consider either cyclosporin or dupilumab. In my experience, cyclosporin approval is achievable for most health plans or does not require a prior authorization. Since neither cyclosporin or dupilumab is approved for urticaria, a shared decision-making discussion would be necessary, emphasizing that current guidelines recommend the calcineurin inhibitor. Reduced potential of side-effects may make this option preferable to the patient.
1. Mauer Metz M, Vadasz Z, Kocatürk E, Giménez-Arnau AM. Omalizumab Updosing in Chronic Spontaneous Urticaria: an Overview of Real-World Evidence. Clin Rev Allergy Immunol. 2020 Aug;59(1):38-45. doi: 10.1007/s12016-020-08794-6. PMID: 32418171; PMCID: PMC7351799.
2. Gericke J, Metz M, Ohanyan T, Weller K, Altrichter S, Skov PS, Falkencrone S, Brand J, Kromminga A, Hawro T, Church MK, Maurer M. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria. J Allergy Clin Immunol. 2017 Mar;139(3):1059-1061.e1. doi: 10.1016/j.jaci.2016.07.047. Epub 2016 Nov 9. PMID: 27838346.
3. Fok JS, Kolkhir P, Church MK, Maurer M. Predictors of treatment response in chronic spontaneous urticaria. Allergy. 2021 Oct;76(10):2965-2981. doi: 10.1111/all.14757. Epub 2021 Feb 27. PMID: 33539587.
Altrichter S, Fok JS, Jiao Q, Kolkhir P, Pyatilova P, Romero SM, Scheffel J, Siebenhaar F, Steinert C, Terhorst-Molawi D, Xiang YK, Church MK, Maurer M. Total IgE as a Marker for Chronic Spontaneous Urticaria. Allergy Asthma Immunol Res. 2021 Mar;13(2):206-218. doi: 10.4168/aair.2021.13.2.206. PMID: 33474856; PMCID: PMC7840871.
4. Altrichter S, Fok JS, Jiao Q, Kolkhir P, Pyatilova P, Romero SM, Scheffel J, Siebenhaar F, Steinert C, Terhorst-Molawi D, Xiang YK, Church MK, Maurer M. Total IgE as a Marker for Chronic Spontaneous Urticaria. Allergy Asthma Immunol Res. 2021 Mar;13(2):206-218. doi: 10.4168/aair.2021.13.2.206. PMID: 33474856; PMCID: PMC7840871.
5. Hamilton RG, Marcotte GV, Saini SS. Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy. J Immunol Methods. 2005 Aug;303(1-2):81-91. doi: 10.1016/j.jim.2005.06.008. PMID: 16045925.
6. Search of: dupilumab | Urticaria - List Results - ClinicalTrials.gov
7. Maurer M, Khan DA, Elieh Ali Komi D, Kaplan AP. Biologics for the Use in Chronic Spontaneous Urticaria: When and Which. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1067-1078. doi: 10.1016/j.jaip.2020.11.043. PMID: 33685605.
Hendricks AJ, Yosipovitch G, Shi VY. Dupilumab use in dermatologic conditions beyond atopic dermatitis - a systematic review. J Dermatolog Treat. 2021 Feb;32(1):19-28. doi: 10.1080/09546634.2019.1689227. Epub 2019 Nov 12. PMID: 31693426.
8. Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, Ballmer-Weber B, Bangert C, Ben-Shoshan M, Bernstein JA, Bindslev-Jensen C, Brockow K, Brzoza Z, Chong Neto HJ, Church MK, Criado PR, Danilycheva IV, Dressler C, Ensina LF, Fonacier L, Gaskins M, Gáspár K, Gelincik A, Giménez-Arnau A, Godse K, Gonçalo M, Grattan C, Grosber M, Hamelmann E, Hébert J, Hide M, Kaplan A, Kapp A, Kessel A, Kocatürk E, Kulthanan K, Larenas-Linnemann D, Lauerma A, Leslie TA, Magerl M, Makris M, Meshkova RY, Metz M, Micallef D, Mortz CG, Nast A, Oude-Elberink H, Pawankar R, Pigatto PD, Ratti Sisa H, Rojo Gutiérrez MI, Saini SS, Schmid-Grendelmeier P, Sekerel BE, Siebenhaar F, Siiskonen H, Soria A, Staubach-Renz P, Stingeni L, Sussman G, Szegedi A, Thomsen SF, Vadasz Z, Vestergaard C, Wedi B, Zhao Z, Maurer M. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022 Mar;77(3):734-766. doi: 10.1111/all.15090. Epub 2021 Oct 20. PMID: 34536239.
Dennis K. Ledford, MD, FAAAAI