Session Title: Free Paper Session 9: AMD III
Session Date/Time: Friday 08/09/2017 | 08:00-09:30
Paper Time: 08:48
Venue: Room 117
First Author: : R.Silva PORTUGAL
Co Author(s): : C. Feller W. Macfadden
Dosing regimens such as treat and extend (T&E) allow patient management at an individualised monitoring intervals, and can assist in reducing the number of clinic visits and injections. Therefore, the T&E regimen can reduce treatment burden of patients, treating physicians, and healthcare systems without compromising visual, morphologic, or safety outcomes compared with the monthly regimen in patients with neovascular age-related macular degeneration (nAMD). The TREND study was designed to assess the efficacy and safety of the ranibizumab 0.5 mg T&E versus the monthly regimen in patients with nAMD.
TREND (NCT01948830) was a 12-month, phase IIIb, prospective, randomised, visual acuity (VA) assessor-masked, multicentre (18 countries), interventional study.
Treatment-naïve nAMD patients (N=650) aged ≥50 years were randomised 1:1 to ranibizumab T&E (n=323) or monthly (n=327) treatment. Patients on the T&E regimen received two initial monthly injections at baseline (Day 1) and Month 1; thereafter, based on disease activity (DA), the treatment interval was shortened by two weeks but never less than four weeks (if DA was present) and extended by two weeks (if DA was absent), with a maximum of a 12-week interval. In the monthly regimen group, treatment visits were scheduled at monthly intervals. The primary objective was to demonstrate non-inferiority of ranibizumab 0.5 mg T&E versus monthly treatment, as assessed by change in best-corrected visual acuity (BCVA) from baseline to the end of study. For the primary efficacy analysis, a non-inferiority margin of 5 letters was applied. Secondary objectives included change in central subfield retinal thickness (CSFT) from baseline to the end of study, treatment exposure, and safety assessments.
Overall, 89.8% (T&E) and 90.2% (monthly) patients completed the study. In the T&E and monthly groups, the patients’ mean age was 75.3 and 75.2 years; baseline BCVA was 59.5 and 60.6 letters; and the CSFT was 504.0 and 497.7 µm, respectively; 91.6% and 92.0% were Caucasian, and both groups had 55.4% female patients. At the end of study, the T&E regimen was non-inferior (p<0.001) to the monthly regimen, with a least squares (LS) mean BCVA change of 6.2 versus 8.1 letters from baseline, respectively. The LS means difference between the treatment groups was −1.9 letters (95% confidence interval: −3.83, 0.07). The mean change in CSFT from baseline at Month 12 was −169.2 µm (T&E; n=291) and −173.3 µm (monthly; n=287). The T&E group required fewer injections (8.7 versus 11.1 [mean]) and post-baseline visits (8.9 versus 11.2 [mean]) than the monthly group. The most common ocular adverse events (AEs) were increase in intraocular pressure (T&E: 8.4%; monthly: 8.6%) and conjunctival haemorrhage (T&E: 4.3%; monthly: 5.8%). Ocular serious AEs were similar between groups (1.2% each).
Ranibizumab 0.5 mg administered according to the T&E regimen was statistically non-inferior and clinically comparable to the monthly regimen in improving BCVA from baseline to the end of study with no new safety findings. Clinical comparability between the treatment groups was supported by a similar reduction in CSFT from baseline to the end of study. Patients in the T&E group required approximately 2.5 fewer mean ranibizumab injections versus those in the monthly group. The TREND study results suggest that the T&E treatment may provide similar benefits to the monthly treatment with fewer injections, thereby reducing treatment burden for patients, clinicians, and healthcare systems.