Hanife RAHMANLAR, Ali ALKAN, Hakkı GÜRSÖZ, Cemile ÜÇGÜL ATILGAN, Mehmet ÇITIRIK

TÜRKİYE’DE YAŞA BAĞLI MAKÜLA DEJENERASYONUNDA ENDİKASYON DIŞI İLAÇ KULLANIMI

Amaç: Türkiye’de yaşa bağlı maküla dejenerasyonu (YBMD) olan hastalarda endikasyon dışı (off-label) ilaç kullanımı için yapılanbaşvuruların demografik özelliklerini değerlendirmek.Materyal ve Metot: 1 Ocak ile 31 Aralık 2013 tarihleri arasında Türkiye İlaç ve Tıbbi Cihaz Kurumu Başkanlığına Türkiye genelindekihastanelerden YBMD’ye bağlı koroid neovaskülarizasyonu olan hastalarda endikasyon dışı ilaç kullanımı (bevasizumab, ranibizumab,aflibercept, verteporfin) için yapılan başvurular geriye dönük olarak incelendi. Olguların dosyaları demografik veriler, önceki tedavirejimleri, başvuru gerekçeleri, ilacın istenilen doz ve kullanımı açısından değerlendirildi.Bulgular: Çalışmaya YBMD tanısı ile endikasyon dışı ilaç başvurusu kabul edilen 64 hasta dahil edildi. Hastaların ortalama yaşı 70,12 ±11,01 yıldı ve %46,9’u erkek, %53,1’i kadındı. Bu başvuruların %39,1’ini ranibizumab, %29,7’sini verteporfin, %18,8’ini aflibercept,%12,5’ini ise bevasizumab oluşturmaktaydı. Başvurular; Ege (%48,4), İç Anadolu (%23,4), Marmara (%25,0) ve Doğu Anadolu (%3,1)bölgelerine aitti. Başvuru yapan hastane dağılımları incelendiğinde ilk üç sırada devlet üniversitesi (%48,4), eğitim ve araştırmahastanesi (%40,6) ve vakıf üniversitesi (%7,8) bulunmaktaydı. Başvuru yapan hastaların 12’si (%18,8) önceden aldığı tedavi rejimiolmayan naif hastalardan oluşmaktaydı. Başvuru nedeni olarak diğer anti-vasküler endotelyal büyüme faktörlerine direnç %64,1 oranıylailk sıradaydı.Sonuç: YBMD tedavisinde off-label ilaç başvuru bilgilerinin değerlendirilerek bu konu ile ilgili gerçek kayıtların saptanması, literatüresağladığı katkıyla birlikte, tedavi seçeneklerimizi gözden geçirmemizi sağlayacaktır.

Off-Label Drug Use in Patients with Age-Related Macular Degeneration in Turkey

Aim: To evaluate the demographic characteristics of patients who use off-label drugs for Age-related Macular Degeneration (AMD) in Turkey. Materials and Methods: The applications for off-label drug use in patients with AMD (bevacizumab, ranibizumab, aflibercept, verteporfin) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were evaluated retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens, reasons for application, dosage and usage of the drug. Results: This study included 64 patients who applied for off-label drug use under the diagnosis of AMD. The mean age of all patients was 70.12 ± 11.01 years and 46.9 % were male, 53.1 % were female. Of these, 39.1 % was ranibizumab, 29.7 % was verteporfin, 18.8 % was aflibercept, and 12.5 % was bevacizumab. Applications belonged to Ege (48.4%), Central Anatolia (23.4%), Marmara (25.0%) and East Anatolia (3.1%) regions. In the distribution of the referring hospitals, the first three hospitals were the state universities (48.4 %), the education and research hospitals (40.6%) and the foundation universities (7.8%) Of patients, twelve (18.8%) were naïve patients with no previous treatment regimen. Resistance to other anti-vascular endothelial growth factors as the cause of admission was in the 1st rank with 64.1%. Conclusion: In the treatment of AMD, determining the off-label drug application information and the actual records related to this subject will give us instructive information about our treatment options as well as its contribution to the literature.

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1. Özcan Büyüktanır BG, Karaosmanoğlu DO. Endikasyon Dışı (off-label) İlaç Kullanımından Doğan Zararlardan İlaç Üreticisinin ve Hekimin Hukuki Sorumluluğu. İnönü Üniversitesi Hukuk Fakültesi Dergisi. 2017; 8: 153-198.
2. Stafford RS. Regulating off-label drug use--rethinking the role of the FDA. N Engl J Med 2008; 358: 1427-9.
3. Bressler NM, Bressler SB, Congdon NG ve ark. Age-Related Eye Disease Study Research Group potential public health impact of age-related eye disease study results: AREDS report no. 11. Arch Ophthalmol 2003;121:1621-4.
4. Ferris FL, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol 1984;102:1640-2.
5. Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT. Increased expression of angiogenic factors in age-related maculopathy. Br. J Ophthalmol 1997;81:154-62.
6. Waisbourd M, Loewenstein A, Goldstein M, Leibovitch I. Targeting vascular endothelial growth factor: a promising strategy for treating age-related macular degeneration. Drug Aging. 2007;24:643-62.
7. Frampton JE. Ranibizumab: A review of its use in the treatment of neovascular age-related macular degeneration. Drugs Aging. 2013;30:331-58.
8. Hurwitz H, Fehrenbacher L, Novotny W, ve ark. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J mEd 2004;350:2335-42.
9. Tolentino MJ, Husain D, Theodosiadis P ve ark. Angiography of fluoresceinated anti-vascular endothelial growth factor antibody and dextrans in experimental choroidal neovascularization. Arch Ophthalmol. 2000;118:78-84.
10. Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve week results of an uncontrolled open-label clinical study. Ophthalmology. 2005;112:1035-47.
11. Moshfeghi AA, Rosenfeld PJ, Puliafito CA ve ark. Systemic bevacizumab (Avastin) theraphy for neovascular-age related macular degeneration twenty-four-week results of an uncontrolled open-label clinical study. Ophthalmology.2006;113:2002- 12.
12. Hejer JS, Brown DM, Chong V ve ark; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology.2012;119:2537-48.
13. Photodinamik theraphy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one year results of 2 randomized clinical trials-TAP report. Treatment of age-related acular degeneration with photodynamic theraphy (TAP) Study Group. Arch Ophthalmol. 1999; 117:1329-45.
14. Schmidt-Erfurth U, Miller JW, Sickenberg M ve ark. Photodynamic theraphy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Arch Ophthalmol. 1999;117:1177-87.
15. Jung K, LePendu P, Chen WS ve ark. Automated detection of off-label drug use. PLoS One 2014; 9: e89324.
16. Kaiser PK, Cruess AF, Bogaert P, Khunti K, Kelly SP. Balancing risk in ophthalmic prescribing: Assessing the safety of anti- VEGF therapies and the risks associated with unlicensed medicines. Graefe’s Arch Clin Exp Ophthalmol. 2012;250(11):1563-71.
17. Yüzbaşıoğlu E. Endikasyon Dışı Tedavi ve Dünyada Durum. Turkiye Klinikleri J Ophthalmol. 2015;8:121-4.
18. Kulkarni AD, Kuppermann BD, Wet age-related macular degeneration. Adv Drug Deliv Rev. 2005;57:1994-2009.
19. Treatment of age-related macular degeneration with photodynamic therapy (TAP) study. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with Verteporfin: one year results of 2 randomized clinical trials- TAP report 2. Arch Ophthalmol. 1999;117:1329-1345.
20. Stokkermans TJ. Treatment of age-related macular degeneration. Clin Eye Vis Care 2000;12:15-35.
21. Manoj S: Why does anti VEGF treatment fail in age related macular degeneration (AMD). Korela Journal of Ophthalmology 2011;23:282-6.
22. Sho K, Takahashi K, Yamada H ve ark. Polypoidal choroidal vasculopathy:incidence, demographic features, and clinical characteristics. Arch Ophthalmol. 2003;121:1392-6.