Astım ve Kronik Ürtikerli Hastalarda Omalizumab'ın ve Şiddetli Astım Hastalarında Mepolizumab'ın Kullanımına İlişkin Gerçek Yaşam Verileri: Geriye Dönük Bir Çalışma

Öz

Bu çalışmanın amacı, şiddetli astım ve kronik spontan ürtiker (CSU) hastalarında omalizumab ve mepolizumab'ın gerçek yaşam etkinliğini değerlendirmek, özellikle tedavi sırasında IgE seviyelerindeki ve eozinofil sayılarındaki değişiklikleri incelemekti. Bu geriye dönük çalışma, biyolojik ajanlarla, omalizumab ve mepolizumab dahil olmak üzere tedavi edilen şiddetli astım veya CSU hastalarını içermektedir. Birincil sonuç ölçümleri serum IgE seviyeleri, eozinofil sayıları, ürtiker aktivite puanları (UAS) ve astım kontrol testi puanları (ACT) idi. Veriler istatistiksel yazılım kullanılarak analiz edildi ve Wilcoxon işaretli sıra testi kullanılarak karşılaştırıldı. Biyolojik ajanlarla tedavi edilen şiddetli astım veya kronik ürtikerli 61 hastayı inceledik. Astımlı hastalar, omalizumab ile yıllık ortalama atak oranında 4'ten 0'a (p<0.001) ve mepolizumab ile 6'dan 1'e (p<0.001) önemli bir azalma gösterdi. Eozinofil sayıları ve ACT puanları mepolizumab ile önemli ölçüde azaldı (p<0.001). Omalizumab'dan mepolizumab'a geçiş yapan altı hasta, tedavi değişikliğinin ilk altı ayında şiddetli astım atakları yaşamadı. CSU'lu hastalar omalizumab'a önemli bir yanıt gösterdi (p<0.001). Toplam IgE seviyeleri, eozinofil sayıları, UAS ve ACT puanları da dahil olmak üzere çeşitli belirteçlerde önemli iyileşmeler gözlemledik, bu da bu tedavilerin her iki durumun semptomlarını etkili bir şekilde yönetebileceğini göstermektedir. Bu bulgular, bu tedavilerin etkili terapötik seçenekler olarak kullanılmasının potansiyel faydalarını vurgulamaktadır.

Anahtar Kelimeler

• Astım
• Immünglobulin E
• Kronik Ürtiker
• Omalizumab
• Mepolizumab

Real-Life Data on the Use of Omalizumab in Patients with Severe Asthma and Chronic Urticaria and Mepolizumab in Patients with Severe Asthma: A Retrospective Study

Öz

This study aimed to assess the real-life effectiveness of omalizumab and mepolizumab in patients with severe asthma and chronic spontaneous urticaria (CSU), explicitly examining changes in IgE levels and eosinophil counts during treatment. This retrospective study involved patients with severe asthma or CSU treated with biologic agents, including omalizumab and mepolizumab. The primary outcome measures were serum IgE levels, eosinophil counts, urticaria activity scores (UAS), and asthma control test scores (ACT). We studied 61 patients with severe asthma or chronic urticaria treated with biological agents. Patients with asthma exhibited a significant reduction in the median annual attack rate from 4 to 0 with omalizumab (p<0.001) and from 6 to 1 with mepolizumab (p<0.001). Eosinophil counts, and ACT scores significantly decreased with mepolizumab (p<0.001). Six patients who transitioned from omalizumab to mepolizumab did not experience severe asthma attacks in the first six months following the treatment switch. Patients with CSU showed a significant response to omalizumab (p<0.001). We observed significant improvements in various markers, including total IgE levels, eosinophil counts, UAS, and ACT scores, indicating that these treatments can effectively manage the symptoms of both conditions. These findings underscore the potential benefits of using these treatments as effective therapeutic options.

Anahtar Kelimeler

• Asthma
• Chronic Urticaria
• Mepolizumab
• Omalizumab
• Total IgE

Kaynakça

1. 1. Agache I, Akdis CA, Akdis M, Canonica GW, Casale T, Chivato T, et al. EAACI Biologicals Guidelines—Recommendations for severe asthma. Allergy. 2020;76(1):14-44.
2. 2. Agache I, Rocha C, Pereira A, Song Y, Alonso‐Coello P, Solà I, et al. Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines. Allergy. 2021;76(1):59-70.
3. 3. Chanez P, Contin-Bordes C, Garcia G, Verkindre C, Didier A, De Blay F, et al. Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic asthma. Respir Med. 2010;104(11):1608-17.
4. 4. Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309-16.
5. 5. Ertas R, Ozyurt K, Atasoy M, Hawro T, Maurer M. The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change. Allergy. 2018;73(3):705-12.
6. 6. Tamer F, Gulru Erdogan F, Dincer Rota D, Yildirim D, Akpinar Kara Y. Efficacy of Omalizumab in Patients with Chronic Spontaneous Urticaria and Its Association with Serum IgE Levels and Eosinophil Count. Acta dermatovenerologica Croatica : ADC. 2019;27(2):101-6.
7. 7. Louis R, Pilette C, Michel O, Michils A, Brusselle G, Poskin A, et al. Variability in total serum IgE over 1 year in severe asthmatics. Allergy Asthma Clin Immunol. 2019;15:20.
8. 8. Li B, Huang M, Huang S, Zeng X, Yuan Y, Peng X, et al. Prediction of clinical response to omalizumab in moderate-to-severe asthma patients using the change in total serum IgE level. J Thorac Dis. 2020;12(12):7097-105.

9. 9. Busse WW, Humbert M, Haselkorn T, Ortiz B, Trzaskoma BL, Stephenson P, et al. Effect of omalizumab on lung function and eosinophil levels in adolescents with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2020;124(2):190-6.
10. 10. Chapman KR, Albers FC, Chipps B, Munoz X, Devouassoux G, Bergna M, et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy. 2019;74(9):1716-26.
11. 11. Liu MC, Chipps B, Munoz X, Devouassoux G, Bergna M, Smith SG, et al. Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respiratory research. 2021;22(1):144.
12. 12. Keating GM. Mepolizumab: First Global Approval. Drugs. 2015;75(18):2163-9.
13. 13. Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390-400.
14. 14. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651-9.
15. 15. Albers FC, Licskai C, Chanez P, Bratton DJ, Bradford ES, Yancey SW, et al. Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma. Respir Med. 2019;159:105806.
16. 16. Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4(7):549-56.
17. 17. Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, et al. The international EAACI/GA(2)LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734-66.
18. 18. The Global Asthma Report 2022. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2022;26(Supp 1):1-104.
19. 19. Hatipoglu U, Subramanian A, Campbell T, Rice R, Mummadi S, Hu B, et al. Intrasubject Variability in Total IgE Levels in Patients with Moderate to Severe Persistent Allergic Asthma Over 1 Year. J Allergy Clin Immunol Pract. 2016;4(4):691-6 e1.
20. 20. Massanari M, Holgate ST, Busse WW, Jimenez P, Kianifard F, Zeldin R. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med. 2010;104(2):188-96.
21. 21. Skiepko R, Zietkowski Z, Lukaszyk M, Budny W, Skiepko U, Milewski R, et al. Changes in blood eosinophilia during omalizumab therapy as a predictor of asthma exacerbation. Postepy Dermatol Alergol. 2014;31(5):305-9.
22. 22. Takaku Y, Soma T, Nishihara F, Nakagome K, Kobayashi T, Hagiwara K, et al. Omalizumab attenuates airway inflammation and interleukin-5 production by mononuclear cells in patients with severe allergic asthma. Int Arch Allergy Immunol. 2013;161 Suppl 2:107-17.
23. 23. Noga O, Hanf G, Brachmann I, Klucken AC, Kleine-Tebbe J, Rosseau S, et al. Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J Allergy Clin Immunol. 2006;117(6):1493-9.
24. 24. Levy ML, Bacharier LB, Bateman E, Boulet LP, Brightling C, Buhl R, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):7.
25. 25. Corren J, Kavati A, Ortiz B, Colby JA, Ruiz K, Maiese BA, et al. Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review. Allergy and asthma proceedings : the official journal of regional and state allergy societies. 2017;38(4):250-63.
26. 26. Henriksen DP, Bodtger U, Sidenius K, Maltbaek N, Pedersen L, Madsen H, et al. Efficacy of omalizumab in children, adolescents, and adults with severe allergic asthma: a systematic review, meta-analysis, and call for new trials using current guidelines for assessment of severe asthma. Allergy Asthma Clin Immunol. 2020;16:49.
27. 27. Tugay D, Top M, Aydin O, Bavbek S, Damadoglu E, Oner Erkekol F, et al. Real-world patient-level cost-effectiveness analysis of omalizumab in patients with severe allergic asthma treated in four major medical centers in Turkey. Journal of medical economics. 2023;26(1):720-30.
28. 28. Yilmaz I, Nazik Bahcecioglu S, Turk M, Tutar N, Pacaci Cetin G, Arslan B. Effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, steroid dependence, and small airways in patients with severe eosinophilic asthma. Turk J Med Sci. 2021;51(4):1953-9.
29. 29. Ozdel Ozturk B, Yavuz Z, Eraslan D, Mungan D, Demirel YS, Aydin O, et al. Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data. Int Arch Allergy Immunol. 2022;183(5):526-38.
30. 30. Long A, Rahmaoui A, Rothman KJ, Guinan E, Eisner M, Bradley MS, et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol. 2014;134(3):560-7 e4.
31. 31. Mota D, Rama TA, Severo M, Moreira A. Potential cancer risk with omalizumab? A disproportionality analysis of the WHO's VigiBase pharmacovigilance database. Allergy. 2021;76(10):3209-11.
32. 32. Ali Z, Egeberg A, Thyssen JP, Sorensen JA, Vestergaard C, Thomsen SF. No association between omalizumab use and risk of cancer: a nationwide registry-based cohort study. The British journal of dermatology. 2022;186(4):746-8.
33. 33. Busse W, Buhl R, Fernandez Vidaurre C, Blogg M, Zhu J, Eisner MD, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol. 2012;129(4):983-9 e6.
34. 34. Yilmaz I, Turk M, Nazik Bahcecioglu S, Tutar N, Gulmez I. Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study. Turk J Med Sci. 2020;50(2):433-41.