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Clinical Review Report: Dexamethasone (Ozurdex): (Allergan Inc.): Indication: For the treatment of adult patients with diabetic macular edema who are pseudophakic [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Nov.

Cover of Clinical Review Report: Dexamethasone (Ozurdex)

Clinical Review Report: Dexamethasone (Ozurdex): (Allergan Inc.): Indication: For the treatment of adult patients with diabetic macular edema who are pseudophakic [Internet].

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Appendix 4Detailed Outcome Data

Table 12Number of Patients Receiving Injections (Pseudophakic Subgroup)

Number of treatments, N (%)MEAD-010MEAD-011

DEX 700

N = 44

Sham

N = 50

DEX 700

N = 42

Sham

N = 51

≥ 1▬▬▬▬
≥ 2▬▬▬▬
≥ 3▬▬▬▬
≥ 4▬▬▬▬
≥ 5▬▬▬▬
≥ 6▬▬▬▬
7▬▬▬▬

DEX = dexamethasone.

Note: Exposure was based on the safety population.

Source: MEAD-010 CSR23, MEAD-011 CSR.24

Table 13Exposure to IOP-Lowering Medication in the Study Eye (Pseudophakic Subgroup)

Pooled Data (MEAD-010 and MEAD-011)

DEX 700

N = 85

Sham

N = 100

Baselinea, n/N (%)▬▬
Year 3 final visitb, n/N (%)▬▬
Any time during the study, n/N (%)▬▬

DEX = dexamethasone; IOP = intraocular pressure.

a

Baseline refers to medications used prior to the first injection.

b

Year 3 final visit includes only those medications marked as ongoing at year three.

Note: Exposure to IOP-lowering medication was evaluated in the safety population.

Source: MEAD-010 CSR23, MEAD-011 CSR.24

Table 14Patients with Glaucoma procedure in the Study Eye (Pseudophakic Subgroup)

Pooled Data (MEAD-010 and MEAD-011)

DEX 700

N = 85

Sham

N = 100

Number of patients with glaucoma procedure during the study▬▬

DEX = dexamethasone.

Notes: Glaucoma procedure includes: trabeculoplasty, Iridotomy, trabeculectomy, iridectomy, and phacotrabeculectomy.

Exposure to glaucoma procedure was evaluated in the safety population.

Source: MEAD-010 CSR,23 MEAD-011 CSR.24

Table 15Visual Acuity Efficacy Outcomes (Pseudophakic Subgroup; ITT Analysis)

OutcomeMEAD-010MEAD-011

DEX 700

N = 44

Sham

N = 50

DEX 700

N = 42

Sham

N = 51

BCVA change from baseline
 At month 3
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 6
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 9
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 12
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 18
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 24
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 30
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At month 36
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
 At last visit
 Baseline, n (%)44 (100)50 (100)42 (100)51 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
BCVA change from baseline by category at last visit
 ≥ 5 and < 15 letter improvement
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
No change (includes a 5-letter improvement or worsening)
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 ≥ 5 and < 15 letter worsening
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 ≥ 15 worsening
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 ≥ 10 letter improvement▬▬▬▬
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 < 10 letter change (includes improvement or worsening)
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 ≥ 10 letter worsening
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
BCVA change from baseline by category at month 12
 ≥ 10 letter improvement
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 < 10 letter change (includes improvement or worsening)
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
 ≥ 10 letter worsening
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
BCVA ≥ 15 letter worsening from baseline at any time during the study
 Proportion of patients, n/N (%)▬▬▬▬
 Difference versus sham▬▬
Per cent of visits with BCVA 15 letter improvement during the study
 Baseline, n (%)▬▬▬▬
 Mean, % (SD)▬▬▬▬
 Difference versus sham▬▬
CRT as measured by OCT change from baselinea
 At last visit
 Baseline, n (%)44 (100)50 (100)42 (100)▬
 Adjusted LS mean change from baseline, microns (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬

BCVA = best-corrected visual acuity; CI = confidence interval; CRT = central retinal thickness; DEX = dexamethasone; ITT = intention to treat; LS = least squares; MD = mean difference; OCT = optical coherence tomography; SD = standard deviation.

a

Based on AUC approach and observed data, missing data were not imputed.

Notes: Last visit refers to either month 39 or month 36 which ever was the final visit.

No adjustments for multiple statistical tests were made for any outcomes in the subgroup of adult patients with DME who were pseudophakic.

LOCF was used to impute missing data unless otherwise specified. Patients without post-baseline BCVA were set to value 0 in the analysis.

Means and mean differences were analyzed using an ANCOVA model stratified by treatment as fixed effects and baseline BCVA as the covariate, with the exception of CRT as measure by OCT outcomes which utilized baseline CRT as measured by OCT as the covariate.

Source: MEAD-010 CSR23, MEAD-011 CSR.24

Table 16Visual Acuity Efficacy Outcomes (Pseudophakic Subgroup; PP analysis)

OutcomeMEAD-010MEAD-011

DEX 700

N = 44

Sham

N = 50

DEX 700

N = 42

Sham

N = 51

BCVA average change from baselinea
 Baseline, n (%)▬▬▬▬
 Adjusted LS mean change from baseline, letters (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬
Per cent of visits with BCVA 15 letter improvement during the studya
 Baseline, n (%)▬▬▬▬
 Mean, % (SD)▬▬▬▬
 Difference versus sham▬▬
CRT as measured by OCT average change from baselinea
 Baseline, n (%)▬▬▬▬
 Adjusted LS mean change from baseline, microns (SD)▬▬▬▬
 Adjusted LS MD versus sham (95% CI)▬▬

BCVA = best-corrected visual acuity; CI = confidence interval; CRT = central retinal thickness; DEX = dexamethasone; LS = least squares; MD = mean difference; OCT = optical coherence tomography; PP = per-protocol; SD = standard deviation.

a

Based on AUC approach and observed data, missing data were not imputed.

Notes: Last visit refers to either month 39 or month 36 which ever was the final visit.

No adjustments for multiple statistical tests were made for any outcomes in the subgroup of adult patients with DME who were pseudophakic.

LOCF was used to impute missing data unless otherwise specified. Patients without post-baseline BCVA were set to value 0 in the analysis.

Means and mean differences were analyzed using an ANCOVA model stratified by treatment as fixed effects and baseline BCVA as the covariate, with the exception of CRT as measure by OCT outcomes which utilized baseline CRT as measured by OCT as the covariate.

Source: MEAD-010 CSR,23 MEAD-011 CSR.24

Table 17Pooled Visual Acuity Efficacy Outcomes (Pseudophakic Subgroup)

OutcomePooled Data (MEAD-010 and MEAD-011)

DEX 700

N = 86

Sham

N = 101

Baseline BCVA
 Baseline, n (%)86 (100)101 (100)
 Mean letters (SD)▬▬
BCVA average change from baseline (ITT)a
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)6.5 ▬1.7 ▬
 Adjusted LS MD versus sham (95% CI)NR P < 0.001
BCVA change from baseline (ITT)
 At month 3
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 6
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 9
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 12
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 18
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 24
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 30
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At month 36
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
 At last visit
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
BCVA change from baseline by category at last visit (ITT)
 ≥ 15 letter improvement
 Proportion of patients, n/N (%)20/86 (23.3)11/101 (10.9)
 Difference versus sham12.4% (1.6 to 23.2) P = 0.024
CRT as measured by OCT change from baseline (ITT)
Averagea
 Baseline, n (%)86 (100)101 (100)
 Adjusted LS mean change from baseline, microns (SD)−131.8 ▬−50.8 ▬
 Adjusted LS MD versus sham (95% CI)NR P < 0.001
Time to ≥ 15-letter improvement in BCVA from baseline,b %57.426.3

BCVA = best-corrected visual acuity; CI = confidence interval; CRT = central retinal thickness; DEX = dexamethasone; ITT = intention to treat; LS = least squares; MD = mean difference; OCT = optical coherence tomography; PP = per protocol; SD = standard deviation.

a

Based on AUC approach and observed data, missing data were not imputed.

b

Cumulative response rate at study end.

Last visit refers to either month 39 or month 36 which ever was the final visit.

No adjustments for multiple statistical tests were made for any outcomes in the subgroup of adult patients with DME who were pseudophakic

LOCF was used to impute missing data unless otherwise specified. Patients without post-baseline BCVA were set to value 0 in the analysis

Means and mean differences were analyzed using an ANCOVA model stratified by treatment and study as fixed effects and baseline BCVA as the covariate, with the exception of OCT retinal outcomes which utilized baseline CRT as measured by OCT as the covariate.

Source: Boyer 201449, MEAD-010 CSR23, MEAD-011 CSR24

Table 18Pooled Visual Acuity Efficacy Outcomes (Pseudophakic with DME ≤ 3 Years Subgroup)

OutcomePooled Data (MEAD-010 and MEAD-011)

DEX 700

▬

Sham

▬

Baseline BCVA
 Baseline, n (%)▬▬
 Mean letters (SD)▬▬
BCVA average change from baseline (ITT)a,b
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
BCVA change from baseline (ITT)
 At last visit
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
BCVA change from baseline by category at last visit (ITT)
 ≥ 15 letter improvement
 Proportion of patients, n/N (%)▬▬
 Difference versus sham▬
CRT as measured by OCT change from baseline (ITT)
Averagea,b
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, microns (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
At last visit
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, microns (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬

BCVA = best-corrected visual acuity; CI = confidence interval; CRT = central retinal thickness; DEX = dexamethasone; LS = least squares; MD = mean difference; OCT = optical coherence tomography; PP = per-protocol; SD = standard deviation.

a

Based on AUC approach and observed data, missing data were not imputed.

Notes: Last visit refers to either month 39 or month 36 which ever was the final visit.

No adjustments for multiple statistical tests were made for any outcomes in the subgroup of adult patients with DME who were pseudophakic.

LOCF was used to impute missing data unless otherwise specified. Patients without post-baseline BCVA were set to value 0 in the analysis.

Means and mean differences were analyzed using an ANCOVA model stratified by treatment as fixed effects and baseline BCVA as the covariate, with the exception of CRT as measure by OCT outcomes which utilized baseline CRT as measured by OCT as the covariate.

Source: MEAD-010 CSR23, MEAD-011 CSR24

Table 19Pooled Visual Acuity Efficacy Outcomes (Pseudophakic with DME > 3 Years Subgroup)

OutcomePooled Data (MEAD-010 and MEAD-011)

DEX 700

▬

Sham

▬

Baseline BCVA
 Baseline, n (%)▬▬
 Mean letters (SD)▬▬
BCVA average change from baseline (ITT)ab
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
BCVA change from baseline (ITT)
 At last visit
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, letters (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
BCVA change from baseline by category at last visit (ITT)
 ≥ 15 letter improvement
 Proportion of patients, n/N (%)▬▬
 Difference versus sham▬
CRT as measured by OCT change from baseline (ITT)
Averagea,b
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, microns (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬
At last visit
 Baseline, n (%)▬▬
 Adjusted LS mean change from baseline, microns (SD)▬▬
 Adjusted LS MD versus sham (95% CI)▬

BCVA = best-corrected visual acuity; CI = confidence interval; CRT = central retinal thickness; DEX = dexamethasone; LS = least squares; MD = mean difference; OCT = optical coherence tomography; PP = per-protocol; SD = standard deviation.

a

Based on AUC approach and observed data, missing data were not imputed.

Last visit refers to either month 39 or month 36 which ever was the final visit.

No adjustments for multiple statistical tests were made for any outcomes in the subgroup of adult patients with DME who were pseudophakic.

LOCF was used to impute missing data unless otherwise specified. Patients without post-baseline BCVA were set to value 0 in the analysis.

Means and mean differences were analyzed using an ANCOVA model stratified by treatment as fixed effects and baseline BCVA as the covariate, with the exception of CRT as measure by OCT outcomes which utilized baseline CRT as measured by OCT as the covariate.

Source: MEAD-010 CSR23, MEAD-011 CSR24

Table 20Harms (Pseudophakic Subgroup)

OutcomeMEAD-010MEAD-011

DEX 700

N = 44

Sham

N = 50

DEX 700

N = 42

Sham

N = 51

AEs, n (%)
Subjects with > 0 AEs▬▬▬▬
 Most common reasona▬▬▬▬
SAEs, n (%)
 Subjects with > 0 SAEs▬▬▬▬
 Most common reasona▬▬▬▬
WDAEs, n (%)
 Subjects with > 0 SAEs▬▬▬▬
 Most common reasona▬▬▬▬
Notable Harms, n (%)
 Most common reason▬▬▬▬
Deaths, n (%)▬▬▬▬

AE = adverse event; DEX = dexamethasone; NA = not available; SAE = serious adverse event; WDAE = withdrawal due to adverse event.

a

Frequency > 5%.

Source: MEAD-010 CSR23, MEAD-011 CSR24

Table 21Pooled Non-Ocular Harms (Pseudophakic Subgroup)

OutcomePooled Data (MEAD-010 and MEAD-011)

DEX 700

N = 85

Sham

N = 100

AEs
Subjects with > 0 AEs, n (%)▬▬
Most common AEsa
Hypertension▬▬
Anemia▬▬
Anxiety▬▬
Headache▬▬
Hypercholesterolemia▬▬
Nasopharyngitis▬▬
Gastroesophageal reflux▬▬
Upper respiratory tract infection▬▬
Urinary tract infection▬▬
SAEs
 Subjects with > 0 SAEs, n (%)▬▬
 Treatment related▬▬
WDAEs
 WDAEs, n (%)▬▬
 Most common reasons▬▬
Notable Harms
Deep vein thrombosis▬▬
Thrombocytopenia▬▬

AE = adverse event; DEX = dexamethasone; NA = not available; SAE = serious adverse event; WDAE = withdrawal due to adverse event.

a

Frequency > 5%.

Non-ocular harms were evaluated in the safety population.

Source: MEAD-010 CSR,23 MEAD-011 CSR.24

Copyright © 2018 Canadian Agency for Drugs and Technologies in Health.

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