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Real-Life Outcomes of Oral Provocation Testing with Alternative NSAIDs in NSAID Hypersensitivity

Yıl 2026, Cilt: 9 Sayı: 1, 40 - 47, 17.03.2026
https://izlik.org/JA92XC27SU

Öz

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of drug hypersensitivity reactions. Identifying safe alternative NSAIDs through oral provocation testing (OPT) is essential for clinical management. The 2025 World Allergy Organization (WAO) classification introduced updated phenotypes, highlighting the need for real-life data on tolerated alternative agents.
Materials and methods:
This retrospective study included 824 adults evaluated for suspected NSAID hypersensitivity between January 2020 and September 2025. Patients were reclassified according to the 2025 WAO criteria. Demographic characteristics, comorbid allergic diseases, culprit drugs, laboratory parameters, and outcomes of OPT with alternative NSAIDs were analyzed.
Results:
The mean age was 44.7 ± 13.2 years, and 65.5% of patients were female. According to the 2025 WAO classification, 48.8% had NSAID-exacerbated cutaneous disease (NECD), 32.2% NSAID-induced urticaria/angioedema (NIUA), and 11.2% single NSAID-induced urticaria/angioedema/anaphylaxis (SNIUAA). Among 704 patients undergoing OPT, tolerance rates were high for meloxicam (96%), nimesulide (97%), and celecoxib (98.6%). The distribution of asthma, rhinitis, urticaria/angioedema, chronic sinusitis, and nasal polyps differed significantly among WAO phenotypes (p < 0.05), whereas tolerance to alternative NSAIDs did not differ between groups (p > 0.05).
Conclusion:
Meloxicam, nimesulide, and celecoxib are well tolerated in most patients with NSAID hypersensitivity. The 2025 WAO classification improves phenotypic stratification, while OPT remains a reliable method for identifying safe alternative NSAIDs in real-life practice.

Kaynakça

  • 1. Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219-1232. Crossref
  • 2. Romano A, Valluzzi RL, Alvarez-Cuesta E, Ansotegui I, Asero R, et al. Updating the classification and routine diagnosis of NSAID hypersensitivity reactions: A WAO Statement. World Allergy Organ J. 2025;18(8):101086. Crossref
  • 3. Barbaud A, Garvey LH, Torres M, Laguna JJ, Arcolaci A, et al. EAACI/ENDA position paper on drug provocation testing. Allergy. 2024;79(3):565-579. Crossref
  • 4. Li L, Bensko J, Buchheit K, Saff RR, Laidlaw TM. Safety, outcomes, and recommendations for two-step outpatient nonsteroidal anti-inflammatory drug challenges. J Allergy Clin Immunol Pract. 2022;10(5):1286-1292.e2. Crossref
  • 5. Demir S, Olgac M, Unal D, Gelincik A, Colakoglu B, Buyukozturk S. Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification. Allergy. 2015;70(11):1461-1467. Crossref
  • 6. Leong CS, et al. Review of NSAID hypersensitivity reactions based on clinical phenotyping. J Clin Rheumatol Immunol. 2024;24(1):1-10.
  • 7. Eraso I, Sangiovanni S, Morales EI, Fernández-Trujillo L. Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: a systematic review of the literature and meta-analysis. PLoS One. 2021;16(3):e0247871. Crossref
  • 8. Ali S, Udrea R, Boustani R, Puiu IA, Corcea SL, Spiru L. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: does age matter? Arch Clin Cases. 2022;9(2):80-88. Crossref
  • 9. Sousa-Pinto B, Fonseca JA, Gomes ER. Frequency of self-reported drug allergy: a systematic review and meta-analysis with meta-regression. Ann Allergy Asthma Immunol. 2017;119(4):362-373.e2. Crossref
  • 10. Doña I, Sáenz de Santa María R, Moreno EM, Bartra J, Torres MJ. An algorithm for the diagnosis and treatment of nonsteroidal anti-inflammatory drugs hypersensitivity, 2024 update. Allergy. 2025;80(4):1183-1186. Crossref
  • 11. Koh YI, Yu JE, Sim DW. Cross-reactive NSAID hypersensitivity: clinical findings from aspirin provocation and alternative drug challenge testing. Clin Transl Sci. 2025;18(9):e70335. Crossref
  • 12. Doña I, Barrionuevo E, Salas M, Laguna JJ, Agúndez J, García-Martín E, et al. NSAIDs hypersensitivity often induces a blended reaction pattern involving multiple organs. Sci Rep. 2018;8(1):16710. Crossref
  • 13. Stehlin F, Prosty C, Mulé A, Al-Otaibi I, Colli LD, et al. Guiding drug provocation testing for ibuprofen hypersensitivity in a pediatric population: development of the I3A risk-stratification tool. J Allergy Clin Immunol Pract. 2025;13(3):583-593.e3. Crossref
  • 14. Rojas-Mejía DV, Silva Espinosa DL, Martínez DM, Ramírez Zuluaga LF, Serrano Reyes CD. Meloxicam and/or etoricoxib could be administered safely in two equal doses during an open oral challenge in patients with nonsteroidal anti-inflammatory drug hypersensitivity. Int Arch Allergy Immunol. 2021;182(5):433-439. Crossref
  • 15. Park SY, Yoo Y, Huh JY, Lee D, Kim K, et al. Safety and outcomes of at-home self-provocation tests in patients with mild nonsteroidal anti-inflammatory drug-induced urticaria/angioedema. Ann Allergy Asthma Immunol. 2023;131(3):356-361. Crossref
  • 16. Weberschock TB, Müller SM, Boehncke S, Boehncke WH. Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature. Arch Dermatol Res. 2007;299(4):169-175. Crossref
  • 17. Domingo MV, Marchuet MJ, Culla MT, Joanpere RS, Guadaño EM. Meloxicam tolerance in hypersensitivity to nonsteroidal anti-inflammatory drugs. J Investig Allergol Clin Immunol. 2006;16(6):364-366.
  • 18. Llanora GV, Loo EX, Gerez IF, Cheng YK, Shek LP. Etoricoxib: a safe alternative for NSAID intolerance in Asian patients. Asian Pac J Allergy Immunol. 2013;31(4):330-333. Crossref
  • 19. Angeletti F, Meier F, Zöller N, Meissner M, Kaufmann R, Valesky EM. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs): a retrospective study. J Dtsch Dermatol Ges. 2020;18(12):1405-1414. Crossref
  • 20. Thalappil S, Al-Nesf M. Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity. Qatar Med J. 2022;2022(2):4. Crossref
  • 21. Defrance C, Bousquet PJ, Demoly P. Evaluating the negative predictive value of provocation tests with nonsteroidal anti-inflammatory drugs. Allergy. 2011;66(11):1410-1414. Crossref
  • 22. Popiolek I, Blasiak M, Kozak A, Pietak E, Bulanda M, Porebski G. Diagnostic value of oral provocation tests in drug hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs and paracetamol. Diagnostics (Basel). 2022;12(12):3074. Crossref

NSAİİ Aşırı Duyarlılığında Alternatif NSAİİ’lerle Oral Provokasyon Testinin Gerçek Yaşam Sonuçları

Yıl 2026, Cilt: 9 Sayı: 1, 40 - 47, 17.03.2026
https://izlik.org/JA92XC27SU

Öz

Amaç:
Nonsteroid antiinflamatuvar ilaçlar (NSAİİ), ilaç aşırı duyarlılık reaksiyonlarının en sık nedenleri arasında yer almaktadır. Güvenli alternatif NSAİİ’lerin belirlenmesinde oral provokasyon testi (OPT) klinik yönetim açısından büyük önem taşımaktadır. 2025 Dünya Alerji Organizasyonu (WAO) sınıflamasında güncellenen fenotip tanımlamaları, gerçek yaşam verilerine olan ihtiyacı artırmıştır. Bu çalışmada, NSAİİ aşırı duyarlılığı olan hastalarda alternatif NSAİİ’lerle yapılan OPT sonuçlarının değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntemler:
Bu retrospektif çalışmaya Ocak 2020–Eylül 2025 tarihleri arasında NSAİİ aşırı duyarlılığı şüphesiyle değerlendirilen 824 erişkin hasta dahil edildi. Hastalar 2025 WAO sınıflamasına göre yeniden sınıflandırıldı. Demografik özellikler, eşlik eden alerjik hastalıklar, sorumlu ilaçlar, laboratuvar bulguları ve alternatif NSAİİ’lerle yapılan oral provokasyon testlerinin sonuçları analiz edildi.

Bulgular:
Hastaların ortalama yaşı 44,7 ± 13,2 yıl olup, %65,5’i kadındı. 2025 WAO sınıflamasına göre hastaların %48,8’i NSAİİ ile alevlenen kutanöz hastalık (NECD), %32,2’si NSAİİ ile indüklenen ürtiker/anjiyoödem (NIUA) ve %11,2’si tek NSAİİ ile indüklenen ürtiker/anjiyoödem/anafilaksi (SNIUAA) grubunda yer aldı. Oral provokasyon testi uygulanan 704 hastada meloksikam (%96), nimesulid (%97) ve selekoksib (%98,6) için yüksek tolerans oranları saptandı. Astım, rinit, ürtiker/anjiyoödem, kronik sinüzit ve nazal polip sıklıkları WAO fenotipleri arasında anlamlı farklılık gösterirken (p < 0,05), alternatif NSAİİ’lere tolerans oranları gruplar arasında benzerdi (p > 0,05).

Sonuç:
Meloksikam, nimesulid ve selekoksib, NSAİİ aşırı duyarlılığı olan hastaların büyük çoğunluğunda iyi tolere edilmektedir. 2025 WAO sınıflaması fenotipik ayrımı güçlendirirken, oral provokasyon testi gerçek yaşam pratiğinde güvenli alternatif NSAİİ’lerin belirlenmesinde güvenilir bir yöntem olmaya devam etmektedir.

Kaynakça

  • 1. Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219-1232. Crossref
  • 2. Romano A, Valluzzi RL, Alvarez-Cuesta E, Ansotegui I, Asero R, et al. Updating the classification and routine diagnosis of NSAID hypersensitivity reactions: A WAO Statement. World Allergy Organ J. 2025;18(8):101086. Crossref
  • 3. Barbaud A, Garvey LH, Torres M, Laguna JJ, Arcolaci A, et al. EAACI/ENDA position paper on drug provocation testing. Allergy. 2024;79(3):565-579. Crossref
  • 4. Li L, Bensko J, Buchheit K, Saff RR, Laidlaw TM. Safety, outcomes, and recommendations for two-step outpatient nonsteroidal anti-inflammatory drug challenges. J Allergy Clin Immunol Pract. 2022;10(5):1286-1292.e2. Crossref
  • 5. Demir S, Olgac M, Unal D, Gelincik A, Colakoglu B, Buyukozturk S. Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification. Allergy. 2015;70(11):1461-1467. Crossref
  • 6. Leong CS, et al. Review of NSAID hypersensitivity reactions based on clinical phenotyping. J Clin Rheumatol Immunol. 2024;24(1):1-10.
  • 7. Eraso I, Sangiovanni S, Morales EI, Fernández-Trujillo L. Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: a systematic review of the literature and meta-analysis. PLoS One. 2021;16(3):e0247871. Crossref
  • 8. Ali S, Udrea R, Boustani R, Puiu IA, Corcea SL, Spiru L. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: does age matter? Arch Clin Cases. 2022;9(2):80-88. Crossref
  • 9. Sousa-Pinto B, Fonseca JA, Gomes ER. Frequency of self-reported drug allergy: a systematic review and meta-analysis with meta-regression. Ann Allergy Asthma Immunol. 2017;119(4):362-373.e2. Crossref
  • 10. Doña I, Sáenz de Santa María R, Moreno EM, Bartra J, Torres MJ. An algorithm for the diagnosis and treatment of nonsteroidal anti-inflammatory drugs hypersensitivity, 2024 update. Allergy. 2025;80(4):1183-1186. Crossref
  • 11. Koh YI, Yu JE, Sim DW. Cross-reactive NSAID hypersensitivity: clinical findings from aspirin provocation and alternative drug challenge testing. Clin Transl Sci. 2025;18(9):e70335. Crossref
  • 12. Doña I, Barrionuevo E, Salas M, Laguna JJ, Agúndez J, García-Martín E, et al. NSAIDs hypersensitivity often induces a blended reaction pattern involving multiple organs. Sci Rep. 2018;8(1):16710. Crossref
  • 13. Stehlin F, Prosty C, Mulé A, Al-Otaibi I, Colli LD, et al. Guiding drug provocation testing for ibuprofen hypersensitivity in a pediatric population: development of the I3A risk-stratification tool. J Allergy Clin Immunol Pract. 2025;13(3):583-593.e3. Crossref
  • 14. Rojas-Mejía DV, Silva Espinosa DL, Martínez DM, Ramírez Zuluaga LF, Serrano Reyes CD. Meloxicam and/or etoricoxib could be administered safely in two equal doses during an open oral challenge in patients with nonsteroidal anti-inflammatory drug hypersensitivity. Int Arch Allergy Immunol. 2021;182(5):433-439. Crossref
  • 15. Park SY, Yoo Y, Huh JY, Lee D, Kim K, et al. Safety and outcomes of at-home self-provocation tests in patients with mild nonsteroidal anti-inflammatory drug-induced urticaria/angioedema. Ann Allergy Asthma Immunol. 2023;131(3):356-361. Crossref
  • 16. Weberschock TB, Müller SM, Boehncke S, Boehncke WH. Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature. Arch Dermatol Res. 2007;299(4):169-175. Crossref
  • 17. Domingo MV, Marchuet MJ, Culla MT, Joanpere RS, Guadaño EM. Meloxicam tolerance in hypersensitivity to nonsteroidal anti-inflammatory drugs. J Investig Allergol Clin Immunol. 2006;16(6):364-366.
  • 18. Llanora GV, Loo EX, Gerez IF, Cheng YK, Shek LP. Etoricoxib: a safe alternative for NSAID intolerance in Asian patients. Asian Pac J Allergy Immunol. 2013;31(4):330-333. Crossref
  • 19. Angeletti F, Meier F, Zöller N, Meissner M, Kaufmann R, Valesky EM. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs): a retrospective study. J Dtsch Dermatol Ges. 2020;18(12):1405-1414. Crossref
  • 20. Thalappil S, Al-Nesf M. Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity. Qatar Med J. 2022;2022(2):4. Crossref
  • 21. Defrance C, Bousquet PJ, Demoly P. Evaluating the negative predictive value of provocation tests with nonsteroidal anti-inflammatory drugs. Allergy. 2011;66(11):1410-1414. Crossref
  • 22. Popiolek I, Blasiak M, Kozak A, Pietak E, Bulanda M, Porebski G. Diagnostic value of oral provocation tests in drug hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs and paracetamol. Diagnostics (Basel). 2022;12(12):3074. Crossref
Toplam 22 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Göğüs Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Zeynep Yegin Katran 0000-0002-6858-6824

Özge Argın 0000-0001-7068-2842

İsmet Bulut 0000-0002-8111-6149

Gönderilme Tarihi 31 Aralık 2025
Kabul Tarihi 17 Şubat 2026
Yayımlanma Tarihi 17 Mart 2026
IZ https://izlik.org/JA92XC27SU
Yayımlandığı Sayı Yıl 2026 Cilt: 9 Sayı: 1

Kaynak Göster

APA Yegin Katran, Z., Argın, Ö., & Bulut, İ. (2026). Real-Life Outcomes of Oral Provocation Testing with Alternative NSAIDs in NSAID Hypersensitivity. Journal of Cukurova Anesthesia and Surgical Sciences, 9(1), 40-47. https://izlik.org/JA92XC27SU
https://dergipark.org.tr/tr/download/journal-file/11303