Ranibizumab for Visual Impairment due to Diabetic Macular Edema: Real-World Evidence in the Italian Population (PRIDE Study)

Abstract

Purpose. An expanded access program (PRIDE study) in Italy to provide ranibizumab 0.5 mg to diabetic macular edema (DME) patients, prior to reimbursement. Methods. Open-label, prospective, phase IIIb study. Majority of patients were not treatment-naïve before enrollment. Patients received ranibizumab as per the EU label (2011). Safety was assessed by incidences of ocular/systemic adverse events (AEs) and serious AEs (SAEs) and efficacy in terms of visual acuity (VA) change from baseline (decimal score or Snellen (20/value)). Results. Overall, 515 patients (83.5%) completed the study. In unilateral/bilateral patients, commonly observed AEs were cardiac disorders (1.3%/1.3%) and nervous system disorders (1.3%/1.1%); SAEs were reported in 4.5%/4.8% of patients. Acute renal failure, lung carcinoma, and cardiac arrest were the causes of death in one unilateral and two bilateral patients. Ranibizumab improved/maintained VA (Snellen (20/value)/decimal scores) in both unilateral (up to −16.7/1.5) and bilateral patients (up to −23.6/1.2) at Month 5, with a mean of 4.15 and 4.40 injections, respectively. Overall, no difference was observed in the VA outcomes and treatment exposure between unilateral/bilateral patients. Conclusions. The PRIDE study provided early ranibizumab access to >600 Italian patients. Ranibizumab was well-tolerated and improved/maintained VA in 40.2%–68.8% patients, with no differences in case of unilateral or bilateral pathology. The study is registered with EudraCT.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema

“…This is quite disappointing compared with the pivotal trials,2 3 5–7 9 13–15 which observed a mean gain of 10.6–11.1 letters at 12 months. DMO observations from smaller open-label prospective, phase IIIb studies such as PRIDE (Efficacy and Safety of Ranibizumab Alone or in Combination With Laser Photocoagulation vs. Laser Photocoagulation Alone in Proliferative Diabetic Retinopathy) (n=515), RELIGHT (Ranibizumab Treatment of Diabetic Macular Oedema With Bimonthly Monitoring After a Phase of Initial Treatment) (n=108) and RETAIN (Long-term Outcomes in Patients with Retinal Vein Occlusion Treated with Ranibizumab) (n=332) observed slightly greater VA acuity gains at >12 months ranging from four to eight letters 16 17. However, the gain at 12 months is similar to real-world studies16 18 and within the range from an analysis of several trials 19…”

Treatment of Diabetic Macular Oedema – Clinical Trial Findings and Real-world Outcomes Data

“…propose that due to higher APTC event rates found in ranibizumab, that such events should also be monitored in future. 12 A recent systematic review and meta-analysis of prolonged monthly anti-VEGF use in DME, the assessment of the highest-level exposure group (patients receiving monthly treatment over two years) revealed a possibly increased risk for death and potentially for cerebrovascular accidents. Therefore, the authors concluded that total exposure to anti-VEGF drugs in patients at high risk for vascular diseases should be taken into consideration.…”

Intravitreal ranibizumab for diabetic macular edema patients with good baseline visual acuity; a real life study

“…Formation of choroidal neovascularization is a common complication of macular laser treatments. The use of macular photocoagulation has become questionable since observing the promising outcomes of the use of anti-VEGF agents in visual and anatomical outcomes in the treatment of DME and their effectiveness in slowing the progression of diabetic retinopathy (4)(5)(6)(7)(8)(9). In particular, the risk of enlarging scars might be an important disadvantage in the subgroup of patients with DME but a better VA.…”

“…Ranibizumab has been proven to be effective in various DME treatment regimens that were monthly, pro re nata (PRN), treat and extend, etc. (4)(5)(6)(7)(8)(9)(10). In pivotal multicenter studies, it has been demonstrated that in the first 12 months of treatment, a mean of 8 to 9 ranibizumab injections was required; however, the mean injection number dramatically decreased after the first year (4)(5)(6)(7)(8).…”

“…In pivotal multicenter studies, it has been demonstrated that in the first 12 months of treatment, a mean of 8 to 9 ranibizumab injections was required; however, the mean injection number dramatically decreased after the first year (4)(5)(6)(7)(8). Usually, it is not possible to follow the strict follow-up and retreatment criteria of these studies in real life (9,10). Additionally, only patients with a visual acuity (VA) between 20/32-20/40 and 20/320 were included in these key studies, and it is unclear what the treatment outcomes are in patients with a VA better than 0.6 in decimals who require intravitreal anti-VEGF therapy (4)(5)(6)(7)(8).…”