Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME)

Jean Francois Korobelnik, Jos Kleijnen, Shona H. Lang, Richard Birnie, Regina M. Leadley, Kate Misso, Gill Worthy, Dominic Muston, Diana V Do

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA. Methods: A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one 'head-to-head' study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies). Results: There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45-6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52-7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29-3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants. Conclusions: Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a number of limitations which are inherent in indirect data comparisons.

Original languageEnglish (US)
Article number52
JournalBMC Ophthalmology
Volume15
Issue number1
DOIs
StatePublished - May 15 2015

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Macular Edema
Dexamethasone
Therapeutics
Visual Acuity
Odds Ratio
Confidence Intervals
Bayes Theorem
aflibercept
Diabetic Retinopathy
Safety
Ranibizumab

Keywords

  • Diabetic macular edema (DME)
  • Intravitreal aflibercept
  • Intravitreal ranibizumab
  • Meta-analysis
  • Systematic review

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME). / Korobelnik, Jean Francois; Kleijnen, Jos; Lang, Shona H.; Birnie, Richard; Leadley, Regina M.; Misso, Kate; Worthy, Gill; Muston, Dominic; Do, Diana V.

In: BMC Ophthalmology, Vol. 15, No. 1, 52, 15.05.2015.

Research output: Contribution to journalArticle

Korobelnik, JF, Kleijnen, J, Lang, SH, Birnie, R, Leadley, RM, Misso, K, Worthy, G, Muston, D & Do, DV 2015, 'Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME)', BMC Ophthalmology, vol. 15, no. 1, 52. https://doi.org/10.1186/s12886-015-0035-x
Korobelnik, Jean Francois ; Kleijnen, Jos ; Lang, Shona H. ; Birnie, Richard ; Leadley, Regina M. ; Misso, Kate ; Worthy, Gill ; Muston, Dominic ; Do, Diana V. / Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME). In: BMC Ophthalmology. 2015 ; Vol. 15, No. 1.
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AU - Korobelnik, Jean Francois

AU - Kleijnen, Jos

AU - Lang, Shona H.

AU - Birnie, Richard

AU - Leadley, Regina M.

AU - Misso, Kate

AU - Worthy, Gill

AU - Muston, Dominic

AU - Do, Diana V

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N2 - Background: This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA. Methods: A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one 'head-to-head' study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies). Results: There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45-6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52-7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29-3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants. Conclusions: Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a number of limitations which are inherent in indirect data comparisons.

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