Off-Label Uses of Ranibizumab and Aflibercept for Age-Related Macular Degeneration in Turkey.

Purpose: To evaluate the clinical and demographic aspects of off-label drug use applications for age-related macular degeneration (AMD) in Turkey. Methods: Applications for off-label drug use in the treatment of AMD to the Turkish Medicines and Medical Devices Agency (TITCK) in 2018 were retrospectively analyzed. Demographic characteristics, requested drugs, previous treatment regimens, and reasons for applications were evaluated. Results: The mean age of the patients (n = 209) was 64.9 ± 15.7 years, of which 48.8% were male and 51.2% were female. Ranibizumab (n = 113) comprised 54.1% and aflibercept (n = 96) 45.9% of off-label use applications. No application was made for bevacizumab. The most frequent reasons for application were switchback (49.3%), nonreimbursement of indicated drugs in cases under 50 years of age (24.4%), and failure to complete the loading dose (14.4%). Conclusions: Ranibizumab was the most requested off-label drug for AMD. There was no application for off-label bevacizumab since its use does not require approval from TITCK. In Turkey, new rules were established for the reimbursement of intravitreal drugs for AMD in 2019. Three doses of intravitreal bevacizumab were required initially for aflibercept and ranibizumab to be covered for reimbursement. There is not enough data in the English literature regarding the off-label use of ranibizumab and aflibercept for AMD. This study provides information about drug regulations and the off-label treatment options preferred by physicians for AMD in Turkey.

Biological therapy for ocular Behçet's disease with off-label drug prescription in Turkey.

OBJECTIVE: The use of biological agents in the treatment of ocular Behçet's disease has recently become more frequent. The use of two agents, infliximab (IFX) and adalimumab (ADA), for the treatment of Behçet's disease requires prior approval by the Turkish Medicines and Medical Devices Agency. We report on a review of such applications with a view to informing on how such agents are used off-label in Turkey. METHODS: Prescriptions for off-label use of IFX or ADA sent from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency in 2018 were evaluated. Demographic data, previous treatment regimens and reasons for referral were extracted from the files of the cases. RESULTS: A total of 662 patients were considered for off-label use of IFX or ADA for the treatment of ocular Behçet's disease. The mean age of the patients was 35.7±10.8 years (range 12-76); 61.5% of patients were men and 38.5% were women. Of the applications, 345 (52.1%) were for IFX and 317 (47.9%) for ADA. Among the referring hospitals, the public university hospitals ranked first, accounting for 77.9% of IFX and 88.6% of ADA prescriptions. Most applications were made after the failure of conventional therapy, which included steroids and immunosuppressive agents. CONCLUSION: IFX and ADA are rarely used as initial therapy. Stepwise treatment is still preferred in the treatment of ocular Behçet's disease in Turkey. Our report informs on the management of this difficult-to-treat condition.

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey.

WHAT IS KNOWN AND OBJECTIVE: Retinal vein occlusion (RVO) is one of the most common causes of vision loss. Anti-vascular endothelial growth factor (anti-VEGF) drugs, ranibizumab and aflibercept, and corticosteroid implants are approved treatment options for RVO-related macular edema (ME) in Turkey. To the best of our knowledge, there is no data regarding the off-label use of these drugs for RVO in English literature. We aimed to evaluate the clinical and demographic characteristics of off-label drug use applications in Turkey for RVO. METHODS: Applications made to the Turkish Medicines and Medical Devices Agency between January 1 and December 31, 2018, for the use of off-label drugs (ranibizumab, aflibercept, dexamethasone implant) for the diagnosis of RVO from hospitals across Turkey were retrospectively analysed. Data of the applications, such as demographic characteristics, previous treatment regimens, reasons for applications, applicant hospitals and their regions, were recorded. RESULTS: There were 291 approved applications for RVO. The mean age of the patients was 64.88 ± 10.78 years, 48.8% were male, and 51.2% were female. Of these applications, 44.7% were for aflibercept, 35.7% for ranibizumab and 19.6% for dexamethasone implant. No application was made for bevacizumab since it could be used without needing for an application. The most common reasons for applications were due to dose limitations, failure to complete loading doses, and glaucoma, respectively. In terms of the distribution of the applicant hospitals, public university hospitals ranked first with 72.5%, training and research hospitals ranked second with 14.7% and foundation university hospitals ranked third with 13.1% rates. WHAT IS NEW AND CONCLUSION: The practice of drug use in RVO in Turkey has changed as of the beginning of 2019. Stepwise therapy has been accepted by the drug regulatory agency Turkish Medicines and Medical Devices Agency. Utilization of licensed drugs, aflibercept, ranibizumab and dexamethasone has been allowed only after administration of 3 doses of intravitreal bevacizumab. After 3 doses of bevacizumab, the physician may continue either with bevacizumab again or a dexamethasone implant. If there is a reason such as the presence of glaucoma, the physician may skip dexamethasone and switch to aflibercept and ranibizumab, but in this case, dexamethasone cannot be administered to the patient for life. The evaluation of the off-label treatments of RVO, which is one of the most frequently followed diseases in retina clinics, not only contributes to the literature but also provides information regarding the most frequently applied treatments and the physicians' off-label drug preferences for RVO.

Off-label uses of Aflibercept, Ranibizumab and Dexamethasone implant for diabetic retinopathy in Turkey.

Objective: Diabetic retinopathy (DRP) is the most common retinal vascular disease leading to blindness. There is limited data about the off-label drug use for DRP and diabetic macular edema (DME) in literature. The aim of the article was to evaluate the applications for off-label drug use in patients with DME and DRP in Turkey in terms of demographic and clinical characteristics. Methods: Applications for off-label drug use from hospitals across Turkey to the Turkish Medicines and Medical Devices Agency for DRP in 2018 were reviewed retrospectively. Results: 112 approved applications for 167 eyes were included in our study. The mean age of the cases was 61.24 ± 10.23 years, of them 57.1% were males and 42.9% were females. Of these applications, 41.1% were for aflibercept (n:46), 33.9% for ranibizumab (n:38), and 25% for dexamethasone implant (n:28). There was no application for bevacizumab. In terms of referring hospitals, public university hospitals were in the first place with a rate of 70.5%. The most common reasons for applications were drug switchback request and failure to complete loading dose, respectively. Discussions: DRP treatment can sometimes be challenging. The effectiveness of the intravitreal drugs may decrease over time and drug switching may be necessary. In Turkey, intravitreal drugs are only approved and reimbursed for DRP patients in case of macular edema. Off-label drug use may be preferred in non-approved indications and for reasons such as the need for additional drug doses to the determined limits. However, permission must be obtained from TMMDA for off-label drug use in Turkey. Conclusion: Anti-vascular endothelial growth factor drugs are the first-line treatment options for DME. TMMDA currently approves stepwise therapy for diabetic macular edema, initiated with bevacizumab. Bevacizumab administration does not require approval for off-label application. Additionally, ranibizumab, aflibercept, and dexamethasone implant are reimbursed only in case of failure to respond to 3 doses of bevacizumab injection. Our report provides information about off-label drug preferences and drug use regulations in DRP treatment in Turkey. Abbreviations:DME = diabetic macular edema, DRP = Diabetic retinopathy, FFA = fundus fluorescein angiography, TMMDA = Turkish Medicines and Medical Devices Agency, VEGF = vascular endothelial growth factor.