Off-label use of bevacizumab in age-related macular. Some pharmaceutical aspects related to the clinical practice

REAL JP, DER OHANNESIAN M, PALMA SD, GRANERO G

Rosario

Congreso; 2º Reunión Internacional de Ciencias Farmacéuticas. RICifa 2010; 2012

INTRODUCTION Off-label use is not illegal and is quite common in some specialties. It provides important advantages particularly when approved treatments have failed or do not exist. Besides, the drugs used in this way may not be covered by medical insurance, thus compromising the access to the medicine An example of off-label use, is the treatment of Age-related macular degeneration (AMD), the leading cause of severe visual loss in the developed world. Ranibizumab (RNB) and Bevacizumab (BVZ) are the drugs that have proven most effective in the treatment of AMD. Although both was derived from the same molecule and sharing the same mechanism of action, RNB was licensed for AMD and the other not. There is significant volume of literature that suggests that intravitreal injections of BVZ can be an effective and safe treatment with similar results to those obtained with RNZ However, if we consider that regardless of the intrinsic efficacy of these drugs, such treatments only slow the progression and reactivation of the disease, delays or restrictions in access to the medicines may influence the final effectiveness of the treatments. Patients with different access way may have different barriers to access of treatment, and hence, different outcomes. The purpose of this work was to evaluate the use and the effects of intravitreal Bevacizumab (BVZ) and intravitreal Ranibizumab (RNB) for the treatment of neovascular age-related macular degeneration (AMD) in clinical practice in Argentine. MATERIALS AND METHODS At three ophthalmologic centers of Córdoba, Argentina, a retrospective analysis of charts of 96 cases with previously untreated exudative AMD, who were treated with RNB or BVZ between January 2009 and December 2011, was conducted. Main outcomes measured included time delay and mean visual-acuity change between diagnosis and treatment, mean number of injections and follow-up examinations and the major clinical outcomes (mean VA change and proportion of patient who lost <15 letters and proportion of patients who gained > 15 letters) at 3 month, 6 month and 1 year of follow-up RESULTS AND DISCUSION: The delay time between diagnostic and treatment and the decrease in visual acuity in this period were significantly higher for patients treated with RNB than those one treated with BVZ (153.8 vs. 36.06 days, p<0.0001),(-13.01 vs. -5.46 letters, p<0,01).After initiation of treatment, there was a significant improvement in visual acuity for both groups, with a difference in favor of BVZ but not statistical significant (+10.06 vs. +6.27 letters p=0.097). Both groups showed a significant decrease of follow-up examinations in the second half of the follow-up period and a drop in VA in the same period. Throughout the year of treatment, BVZ-group received significantly more injections than RNB-group (4.71 vs 2.98 p <0.0001) and also had better clinical outcomes (table) CONCLUSIONS: The access to treatment, conditioned by the bureaucratic aspects, can be a key factor for success of therapy. In this sense, use off-label BVZ offers patients the option to get best results but it is not the drug itself but the difference in restrictions when a dose is required. TABLE : Clinical Outcomes at different times: Outcome Time point Bevacizumab all eyes Ranibizumab all eyes p value Mean Change in VA Score from baseline (ETDRS letters) Initiation -5,75 (SD:9,96) -13,01 (SD:13,82) 0,003 3 months 4,32 (SD:14,1) -6,74 (SD:16,73) 0,001 6 months 2,5 (SD:14,23) -6,4 (SD:19,36) 0,01 12 months -0,27 (SD:17,46) -8,87 (SD:20,68) 0,039 % Cases that lost <15 letters (Nº cases) Initiation 81% (42) 57% (25) 0,01 3 months 92% (48) 64% (28) 0,001 6 months 90% (47) 64% (28) 0,002 12 months 80% (32) 56% (22) 0,024 % Cases that gained >=15 letters (Nº cases) Initiation - - - 3 months 21% (11) 7% (3) 0,08 6 months 17% (9) 14% (6) 0,8 12 months 18% (7) 10% (4) 0,5 ETDRS=Early Treatment Diabetic Retinopathy Study ; SD=standard deviation; VA =visual acuity; Initiation=first injection visit; 3 months, 6 months, 12 months= visit closest to 90, 183, and 365 days from first injection