Ranibizumab

The drug is injected intravitreally (into the vitreous humour of the eye) according to the manufacturer once a month. If monthly injections are not feasible, the regimen may be reduced to 1 injection every 3 months after the first 4 months.[1]

In age related macular degeneration several administration regimens are used. It is delivered at a fixed or variable frecuency: monthly, every two or three months, or as needed for the patient (PRN). Another scheme is used where treatment is initially monthly, then delivered with increasing intervals and re-injected if recurrence (treat and extend). It has been demostrated that people who received monthly injections had a discrete better visual acuity than people who received injections as needed; but clinical trials did not find differences between the PRP and treat and extend regimens. The people at monthly scheme receive more inyections, and the more these are administrated, more risk of rare side effects like infection.[12]

Dosing every 3 months is linked to a loss of approximately 5 letters (1 line) in visual acuity for the following 9 months as compared with dosing on a monthly basis. Large phase 3 clinical trials (MARINA and ANCHOR) which randomized patients with wet macular degeneration showed that 95% of ranibizumab-treated patients maintained visual acuity compared with 62% of those administered placebo (P < .01) at 1 year; moreover, up to 40% demonstrated an improvement in vision of at least 3 lines. Vision maintenance and loss were defined as a loss of less than 15 letters and a gain of 15 or more letters in visual acuity, respectively, as measured using the Early Treatment of Diabetic Retinopathy eye chart.[13]

Concerning repeated injections after retinal vein occlusion two different procedures are in use, fixed schedule or pro re nata (PRN = as needed). The fixed schedule usually starts with three monthly spaced injections followed by further ones in monthly or slightly extended intervals depending on the patient’s response. In PRN repeated injections are only given as needed.

Studies comparing the two procedures found that in PRN fewer injections were given with no difference in outcome.[14][15][16] In a survey from 2017 in Japan, 28 of 34 retina specialists (82.4%) said they used PRN, irrespective of the severity of the case.[17] Similar surveys in other countries have (as of 2020) not yet been published.

Its effectiveness is similar to that of bevacizumab.[3][18] Its rates of side effects also appear similar.[7] However, ranibizumab typically costs $2,000 a dose, while the equivalent dose of bevacizumab typically costs $50.[19][20][21][22]

On November 3, 2010, The New York Times reported that Genentech began offering secret rebates to about 300 ophthalmologists in an apparent inducement to get them to use more ranibizumab rather than their less expensive bevacizumab. This may have been in anticipation of the results of the CATT clinical trial,[20] which was sponsored by the National Eye Institute, and compared the relative safety and efficacy of ranibizumab and bevacizumab in treating AMD. In 2008, bevacizumab cost Medicare only $20 million for about 480,000 injections, while ranibizumab cost Medicare $537 million for only 337,000 injections.[23] A small study showed no superior effect of ranibizumab versus bevacizumab in direct comparison.[24] The initial results of the larger Comparison of Age-related Macular Degeneration Treatments Trials (CATT) trial were published in the New England Journal of Medicine in May 2011.[20] The trial showed that the two drugs "had equivalent effects on visual acuity when administered according to the same schedule;" however, serious adverse events were more common in the bevacizumab arm of the trial.

The results of several subsequent head-to-head trials of the two anti-VEGF treatments were later published, and the overall results reinforced CATT's findings. The two therapies performed equally at restoring visual acuity according to a 2012 meta-analysis,[25] and also in the IVAN trial, alone and in the investigators' meta-analysis pooling its own results with CATT's.[26] A 2012 meta-analysis focused specifically on safety issues concluded that the rates of several adverse events were higher with bevacizumab, although the absolute rates of ocular serious adverse events were low with both therapies: ocular adverse events were about 2.8 times as frequent with bevacizumab than with ranibizumab, and "The proportion of patients with serious infections and gastrointestinal disorders was also higher." The authors concluded that " clinicians and patients should continue to carefully weigh-up the benefits and harms when choosing between the two treatment options. We also emphasize the need for studies that are powered not just for efficacy, but for defined safety outcomes based on the signals detected in this systematic review".[18]