Patients treated for diabetic macular oedema with ranibizumab in the UK National Health Service (NHS) are getting benefits similar to those seen in clinical trials, according to a new study
Patients treated for diabetic macular oedema with ranibizumab in the UK National Health Service (NHS) are getting benefits similar to those seen in clinical trials, a new study suggests.
Treated on a pro re nata (as needed) basis, the patients gained a mean of 6.6 ETDRS letters in 12 months in the study, reported Ranjan Rajendram and colleagues at Moorfields Eye Hospital in London, UK. They published their findings in the American Journal of Ophthalmology.
"This Moorfields study on a cohort of 200 eyes shows that results from landmark clinical trials are reproducible in clinical practice to a large extent," they wrote.
Although anti-vascular endothelial growth factor (VEGF) treatments have achieved impressive results in clinical trials, researchers have wondered whether the same effects can be achieved in a real-world setting where patients are less carefully chosen and don't have as much support in getting to appointments.
To see how well the treatment is working in the NHS, Dr Rajendram and colleagues retrospectively analysed records on 200 eyes in 164 patients.
The patients had a mean age of 65.11 years, and 63.4% were women. 36% were white, 28.7% were southeast Asian, 9.2% were Afro-Caribbean, and the rest were designated as "other" or "unknown."
98% of the patients had type 2 diabetes and 2% had type 1 diabetes.
Their mean baseline visual acuity was 54.5 letters. Their mean baseline central sub field thickness was 490.16 μm. Their mean baseline macular volume was 10.46 mm3.
The patients received treatment according to the European Union summary of product characteristics label for ranibizumab. The initial loading phase of injections consisted of three consecutive monthly intravitreal injections of 0.5 mg ranibizumab, followed by injections as needed.
Re-treatment was not based on strict criteria, but in general treatment was withheld when there was no further improvement in visual acuity attributable to ranibizumab treatment and/or the macular fluid was stable on two consecutive visits. Patients were monitored every 2 months, and ranibizumab treatment was resumed if disease activity was observed until visual acuity and macular fluid were judged stable.
Over the course of 12 months, the patients received a mean of 7.2 injections.
The visual acuity benefit in these patients was similar to that in the RESTORE clinical trial, where patients gained 6.8 letters. It was superior to the 4.8 letter gain seen in the RELIGHT study, but less than the 9 letters in the Protocol I letter (which included prompt or deferred laser arms).
The proportion of patients who gained at least 15 letters, and the proportion who gained at least 10 letters, were also similar in this study when compared to these clinical trials.
The proportions of those who lost at least 15 letters, or at least 10 letters, were greater in this study than in the clinical trials. The investigators attributed this difference to the inclusion of patients with ocular co-morbidities that were excluded from the clinical trials.
Eyes that received prior macular laser in this study gained 7.5 letters, a similar result to those in the RESTORE trial, where patients who received macular laser prior to entry in the trial gained 6.4 letters.
The eyes in this study that received macular laser gained 11.6 letters, compared with 5.9 letters in those that did not receive laser. However, this difference was not statistically significant (p=0.0557). Since only 23 eyes received laser in this study, the investigators wrote, they could not draw definitive conclusions about this population.
The patients with the lowest visual acuity at baseline enjoyed the highest visual acuity gain, as did those in the RESTORE and RELIGHT trials.
Those with baseline visual acuity of more than 73 letters lost 4.3 letters, but the results in this subgroup of 17 eyes was not statistically significant (p=0.22).
Central subfield thickness in this study decreased by 133.9 μm, which was similar to the 131 μm reduction in Protocol I with prompt laser (137 μm with deferred laser). It was better than the 118.7–128.3 μm reduction in the RESTORE trial and the 127.1 μm reduction in the RELIGHT trial.
The number of injections was also similar to the 6.8–7.0 injections in the RESTORE trial, though it was slightly fewer than the 8–9 injections in the Protocol I study.
The results were also similar to those in other real-world studies. For example, a study in Denmark on 62 eyes receiving an average of five injections over 9–15 months gained an average of 5 letters and lost 98 μm in central subfield thickness.
The investigators attributed the lower gain in visual acuity in this study compared with the Protocol I trial to the long duration of diabetic macular oedema already treated with macular laser prior to ranibizumab becoming available through the NHS, the inclusion of a broad range of severity of diabetic retinopathy and the lower number of injections.
They also cited the challenges of clinical practices where co-morbidities and complicated schedules could make a consistent treatment schedule difficult.
The investigators acknowledged some limitations to the study. Unrefracted visual acuity recordings and non-referenced optical coherence tomography images performed in non-trial settings were used at successive visits. The 25 clinicians involved might have varied in their retreatment criteria.