Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study

Abstract

Aims: To demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO).

Methods: A 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1-12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile.

Results: Both T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1-12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information.

Conclusions: T&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here.

Trial registration number: NCT01171976.

Keywords: Clinical Trial; Macula; Treatment Lasers; Treatment Medical; Vision.

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Figures

Figure 1

The treat-and-extend (T&E) treatment algorithm. *Scheduled between the T&E visits where no study treatment was administered and no decision for study treatment was made. For the pro re nata (PRN; control) regimen, each monitoring visit was also a potential treatment visit. †Best-corrected visual acuity (BCVA) stable: no BCVA improvement or deterioration noted for three consecutive monthly study visits under treatment. **Patient's BCVA worsened due to diabetic macular oedema (DMO) disease activity. ¶First visit followed 1 month after the visit at which stabilisation (at month 3) was confirmed. BSL, baseline; M, months.

Figure 2

(A) Mean change in best-corrected visual acuity (BCVA) from baseline to months 12 and 24 (full analysis set (FAS)-mean value imputation/last observation carried forward (MV/LOCF)). *p=0.9327 versus pro re nata (PRN); #p=0.1599 versus PRN; Cochran–Mantel–Haenszel (CMH) test (row mean scores statistic) with the observed values as scores. (B) Mean percentage change in central subfield thickness (CSFT) from baseline over time (FAS-MV/LOCF). In (A) and (B), FAS (MV/LOCF) comprised all randomised patients who received at least one application of study treatment (ranibizumab or laser) and had at least one postbaseline efficacy assessment in the study eye. Stratified analysis included baseline visual acuity (≤60 letters, >60 and ≤73 letters and >73 letters) as factors. ETDRS, Early Treatment Diabetic Retinopathy Study.