Slide 1: Humanistic Burden of Retinal Vein Occlusion: A Systematic Literature Review
Humanistic Burden of Retinal Vein Occlusion: A Systematic Literature Review Quan Dong Nguyen MD, MSc,’ Fabiana Q. Silva, MD,? Gillian Sibbring, PhD,* Anna McCormick, PhD,? Steven Sherman, MPH? 1Byers Eye Institute, Stanford University, Palo Alto, California, 7Regeneron Pharmaceuticals, Inc., Tarryto
Slide 2: Disclosures
Disclosures Quan Dong Nguyen reports being a Scientific Advisory Board member for Bausch and Lomb, Genentech, and Regeneron Pharmaceuticals, Inc. Fabiana Q. Silva and Steven Sherman are employees of and stockholders in Regeneron Pharmaceuticals, Inc. Gillian Sibbring and Anna McCormick are employees
Slide 3: Background
Background « RVO (including its subtypes CRVO and BRVO) is the second most common retinal vascular disorder, affecting more than 28 million people worldwide ¢ ME is acommon visually threatening complication of RVO; ME is a major complication of CRVO, and 5%-15% of eyes with BRVO have been reported t
Slide 4: Systematic literature review methods following PICOS framework
Asystematic literature review was conducted to retrieve relevant clinical data from published literature in accordance with the PICOS framework’ Medline and Embase databases were searched via the Ovid search engine to identify relevant RCTs/ observational studies published from January 1, 1990, to M
Slide 5: PICOS eligibility criteria
opulation/problem Adult patients (218 years old) with RVO (bra central, or hemi ntervention treated or best supportive care Any treatment, including but not | ited to pharmacological treatment omparison Any intervention of interest, including active comparators + Placebo or best supportive care utco
Slide 6: Study selection flow diagram
Medline n=596, Reports sought for reti Reports assessed for 3 o 3 4 r) £ Records screened n=3416 rieval (full text) n=449 eligibility n=449 Reports included in review n=25 Records excluded n=29672 Reports not retrieved n=O Reports excluded n=442:> + Non-relevant patient population n=13 Non-relevant
Slide 7: Outcomes Identified
Outcomes Identified NEI VFQ-25 scores * General burden: Impact of RVO on NEI VFQ-25 composite and subscale scores + Effect of treatment: * Change from baseline to post-treatment in NEI VFQ-25 composite scores in patients with RVO + Comparison of post-treatment NEI VFQ-25 composite scores in patients
Slide 8: Impact of RVO types on NEI VFQ-25 scores
Five publications of 4 studies (2 from SCORE 2 RCT in MEfRVO,"? 3 in overall RVO: 1 prospective cohort study,° 1 case-controlled study,* and 1 cross-sectional study*) reported impact of different types of RVO on composite and subscale NEI VFQ-25 scores NEI VFQ-25 composite and most subscale scores w
Slide 9: MEfBRVO/MEfHRVO NEI VFQ-25 changes
Study type MEfBRVO/ 2 VIBRANT! MEfHRVO * Seven publications of 4 RCTs compared post-treatment NEI VFQ-25 composite scores between different treatment strategies in BRVO/HRVO + Improvements in NEI VFQ-25 scores following treatment with anti-VEGF agents when compared with controls were observed in all
Slide 10: VIBRANT: IAI versus laser NEI VFQ-25 scores
Study type IAI 2 mg Q4W (n=917),W24 yay IAI 2 mg Q4W x6 then Q8W (n=91°), W52 [Exon Laser/sham; IAI 2 mg rescue from W24 (Q4W x3 then Q8W) (n=90‘),W52 [EI:Bs) MEfBRVO/ 2 VIBRANT! MEfHRVO MEfBRVO In VIBRANT, IAI numerically improved NEI VFQ-25 composite scores versus laser after Week 24 and laser/IAl
Slide 11: BRAVO: monthly IRI versus sham
Study type IAI 2 mg Q4W (n=917),W24 yay IAI 2 mg Q4W x6 then Q8W (n=91°), W52 [exes Laser/sham; IAI 2 mg rescue from W24 (Q4W x3 then Q8W) (n=90‘),W52 [EI:Bs) IRI 0.3 mg Q4W (n=133),W24 [Ei MEfBRVO +10.4° Sham (n=129),W24 [EEws MEfBRVO/ 2 VIBRANT! MEfHRVO In BRAVO, monthly IRI significantly improved
Slide 12: COMO: IRI versus dexamethasone implant
Study type MEfBRVO/ 2 VIBRANT! MEfHRVO IAI 2 mg Q4W x6 then Q8W (n=91°), W52 [exes Laser/sham; IAI 2 mg rescue from W24 (Q4W x3 then Q8W) (n=90‘),W52 [EI:Bs) IRI 0.3 mg Q4W (n=133),W24 FR RS MEfBRVO +10.4° ‘Sham (n=129),W24 [Ey Dex IV implant (n=154), M12, xe) +7.2° In COMO, NEI VFQ-25 composite sco
Slide 13: BRIGHTER: IRI PRN versus IRI/laser
Study type MEfBRVO/ 2 VIBRANT! MEfHRVO IAI 2 mg Q4W x6 then Q8W (n=91°), W52 [ERA Laser/sham; IAI 2 mg rescue from W24 (Q4W x3 then Q8W) (n=90‘),W52 [EI:Bs) IRI 0.3 mg Q4W (n=133),W24 FR RS MEfBRVO +10.4° Sham (n=129),W24 [EE@! Dex IV implant (n=154), M12 |e) 4+7.2° +8.0 BRIGHTER®” IRI 0.5 mg Q4W x3
Slide 14: MEfCRVO RCTs NEI VFQ-25 composite scores
Study type P. CRUISE'? RCT MEfCRVO ¢ Five publications across 3 RCTs compared post-treatment NEI VFQ-25 composite scores between different treatment strategies in MEfCRVO GALILEO*4 RCT MEfCRVO * Improvements in NEI VFQ-25 composite scores were observed with anti-VEGF agents versus controls in all 5
Slide 15: CRUISE: monthly IRI versus sham
Study type Patients CRUISE‘ MEfCRVO GALILEO*4 MEFCRVO In CRUISE, monthly IRI significantly improved NEI VFQ-25 composite scores after Month6 versus sham COPERNICUS® RCT MEfCRVO 1) 1 2 3 4 5 6 7 8 9 Change from baseline NEI VFQ-25 composite score, points @P<0.01; °P<0.05 versus sham. 1. Varma R et al
Slide 16: GALILEO: IAI versus sham
Study type Patients CRUISE'? MEfCRVO GALILEO*+ MEfCRVO In GALILEO, IAI significantly improved COPERNICUS ROT MEICRVO NEI VFQ-25 composite scores at Weeks 24 and 52 versus sham 10) 1 2 3 4 5 6 7 8 Change from baseline NEI VFQ-25 composite score, points *P<0.01; tP<0.05 versus sham. 1. Varma R et al.
Slide 17: COPERNICUS: monthly IAI versus sham
Study type Patients IRI0.3 mg Q4W (n=130), M6 Byae +6.28 jam (n=127), M6 eox:) CRUISE"? MEfCRVO IRL0.3 mg Q4W to M6 then PRN (n=130), M12 Eyal 46.6 Sham to M6 then IRI 0.5 mg PRN (n=127), M12_ EEX) Al 2 mg Q4W (n=96), W24 Bag GALILEO? MEfCRVO Sham (n=65), W24 JEXiy IAI 2 mg Q4W to W24 then PRN (n=98
Slide 18: Correlations with VA, subscales, utilities and pain
NEI VFQ-25 scores at baseline were generally positively correlated with VA in the worse-seeing/affected eye in MEfBRVO;' improved NEI VFQ-25 composite scores after anti-VEGF treatment were correlated with improved VAin MEfCRVO and non-ischemic CRVO?24 NEI VFQ-25 subscale scores for near and distance
Slide 19: Conclusions
Conclusions Only 25 articles published over a >30-year period were identified on the humanistic burden of RVO and the effect of treatment. Evidence for the impact of treatment on QoL in RVO was relatively strong; however, there was a lack of data on the additional burden of ME on QoL in patients wit