Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study

Abstract

Objective: Because many patients with diabetic macular edema (DME) do not respond to focal/grid laser photocoagulation, the only currently approved treatment, alternatives are needed. Based on encouraging preliminary findings, we aimed to assess efficacy and safety of the anti-tumor necrosis factor (TNF) monoclonal antibody infliximab in this condition.

Research design and methods: This was a single-center, double-blind, randomized, placebo-controlled, crossover study. Eleven patients with sight-threatening DME persisting after two sessions of laser photocoagulation received infliximab (5 mg/kg) intravenously at weeks 0, 2, 6, and 14, followed by placebo at weeks 16, 18, 22, and 30, or vice versa. Blinding was maintained to week 32, when the final assessments were performed. Best corrected visual acuity evaluated by a mixed-models approach for imbalanced crossover design using the percentage difference as the outcome variable was the primary study end point. Data were analyzed on an intention-to-treat basis.

Results: Early Treatment of Diabetic Retinopathy Study (ETDRS) scores dropped from 31.6 +/- 5.1 (mean +/- SD) letters read at baseline to 28.8 +/- 11.6 letters read at week 16 in six placebo-treated eyes and improved to 35.4 +/- 11.2 letters read after infliximab. In contrast, visual acuity improved from 23.5 +/- 10.3 at baseline to 30.4 +/- 13.4 letters read at week 16 in eight infliximab-treated eyes and was sustained at completion of placebo treatment (31.4 +/- 12.1 letters read). The excess visual acuity in infliximab-treated eyes was greater by 24.3% compared with that in placebo-treated eyes (95% CI 4.8-43.7; P = 0.017). Infliximab treatment was well tolerated.

Conclusions: The positive results of this small phase III study suggest that larger and longer term trials should be conducted to assess the efficacy of systemic or intravitreal anti-TNF agent administration for primary treatment of DME.

Trial registration: ClinicalTrials.gov NCT00505947.

Figures

Figure 1

Changes in visual acuity (VA) measured by the number of letters that a patient was able to read from the ETDRS chart from baseline to study end. Eyes of group A and group B were treated initially with placebo followed by infliximab or vice versa, respectively (A). The improvement of visual acuity in infliximab-treated eyes is significantly greater by 24.3% compared with that of placebo-treated eyes, as evaluated by a mixed-models approach for imbalanced crossover design (B).

Figure 2

Sequential OCT images at baseline (A), at completion of placebo treatment (B), and at completion of infliximab treatment (C). The photoreceptor inner/outer segment junction line at the foveola is highly disrupted at week −2 (A, arrow), becomes almost absent at week 16 (B, arrow), and appears partially restored at week 32 (C, arrow).