Dr Somdutt Prasad on Current Management of DME: Learning from Protocol T2 Results
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The document discusses the current management of diabetic macular edema (DME), highlighting the efficacy and safety of various treatment options including anti-VEGF agents like aflibercept and ranibizumab, based on results from the DRCR.net Protocol T study. It outlines treatment recommendations, injection frequency, and visual acuity outcomes after two years, noting that while aflibercept showed slightly better initial improvement, no significant differences were found in long-term outcomes between the treatment groups. Additionally, the document emphasizes the importance of individualized treatment strategies based on the patient's initial visual acuity and co-morbid conditions.
![DRCR.net Protocol T: First head to head study
in DME with three anti-VEGF agents
Study objective: compare the efficacy and safety of intravitreal aflibercept,
intravitreal bevacizumab, and intravitreal ranibizumab for the treatment of
DME in eyes of 660 patients with VA between 20/32 and 20/320
ClinicalTrials.gov. Available from: http://clinicaltrials.gov/ct2/show/NCT01627249 [Accessed 27 October 2014]; Wells JA, et al. NEJM 2015, epub ahead of print
DME, diabetic macular edema; DRCR.net, Diabetic Retinopathy Clinical Research Network; NEI, National Eye Institute; VA, visual acuity; VEGF, vascular endothelial growth factor](https://image.slidesharecdn.com/currentmanagementofdmelearningfromprotocolt2results-160427044436/85/Dr-Somdutt-Prasad-on-Current-Management-of-DME-Learning-from-Protocol-T2-Results-18-320.jpg)
Dr Somdutt Prasad on Current Management of DME: Learning from Protocol T2 Results
- 1. Current Management of DME: Learning from Protocol T2 results Somdutt Prasad MS FRCSEd FRCOphth FACS Senior Consultant Ophthalmologist AMRI Medical Centre & Fortis Medical Centre Kolkata, India somprasad@gmail.com +91 7044 06 7754
- 2. Diabetes • 1550 BC - Ebers Papyrus of ancient Egypt • 171 million worldwide • India – 2000 - 31.7 million • 366 million in 2030 – Maximum increase in India – 79.4 million India – 42.3 million China
- 3. Life Expectancy of Function (Years) Behaviour & Environment Good Bad VitalFunction% Failure 0 100 10025 50 75
- 6. Avastin Ziv –Aflibercept or Zaltrap Aflibercept or EyeLeaRanibizumab Lucentis / Accentrix Biosimilar - Razumab
- 7. DME patient population is younger than nAMD patients, and has many associated co-morbid conditions 1. Petrella RJ, et al. J Ophthalmol 2012;159167 2. Bandello F. Presented at COPHy 2014, Lisbon, Portugal Average age at diagnosis DME patients are of working age and require long-term management 80 years2 AMD 50-60 years1,2 DME Disease driven by Age Diabetes2 DME patients often present with co-morbidities
- 8. FDA approval - drugs for DME • Ranibizumab - August 2012 • Aflibercept – March 2015 • Bevacizumab - unlicensed
- 10. Steroids • Triamcinolone – Pseudophakic eyes – Resistant cases • Dexamethasone – Ozurdex • Fluocinolone Acetonide – Iluvien, Retisert
- 11. American Journal of Ophthalmology 2014 157, 505-513.e8DOI: (10.1016/j.ajo.2013.11.012)
- 12. Ranibizumab • 10 RCTS in DME – READ-2 – REVEAL – RESOLVE – RESTORE – RISE & RIDE – DRCRNet trial • 2 years ≥10 letters gain in BCVA • No difference between – Ranibizumab + prompt laser (deferred laser worse) – Laser alone – DRCRNet Protocol T
- 13. Bevacizumab • 8 RCTS in DME – BOLT Avastin vs Laser • N=80, two years • iVB +8.6 letters • Laser -0.5 letters
- 15. Key points • Ranibizumab injections – monthly for 3 visits – then as needed depending on VA (with or without OCT) stability • Follow-up monthly for 6-12 months • Once visual stability maintained for 3 consecutive visits, follow-up intervals can be prolonged to between 2 and 4 months
- 16. Key points…Laser • If response to anti-VEGF treatment is unsatisfactory – ‘rescue’ • DME not involving center
- 17. Key points…Vitrectomy • IF VMT shown on spectral domain OCT AND Vision affected • Role of adjunctive antiVEGF, steroid, laser
- 18. DRCR.net Protocol T: First head to head study in DME with three anti-VEGF agents Study objective: compare the efficacy and safety of intravitreal aflibercept, intravitreal bevacizumab, and intravitreal ranibizumab for the treatment of DME in eyes of 660 patients with VA between 20/32 and 20/320 ClinicalTrials.gov. Available from: http://clinicaltrials.gov/ct2/show/NCT01627249 [Accessed 27 October 2014]; Wells JA, et al. NEJM 2015, epub ahead of print DME, diabetic macular edema; DRCR.net, Diabetic Retinopathy Clinical Research Network; NEI, National Eye Institute; VA, visual acuity; VEGF, vascular endothelial growth factor
- 19. Randomization 19 Bevacizumab (1.25 mg) N = 218 Aflibercept (2.0 mg) N = 224 Ranibizumab (0.3 mg) N = 218 Randomly Assigned Eyes (one per participant): N = 660 N = 206 (94%)N = 208 (93%) N = 206 (94%)One Year 97%94% 96% One Year Excluding Deaths Baseline
- 20. 1st year - Topline results • Clinically meaningful VA improvement with all three medications – +13.3 letters with Aflibercept, – +11.2 with Ranibizumab, – +9.7 with Bevacizumab
- 21. 1st year - Topline results…2 • When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. • At worse levels of initial visual acuity, Aflibercept was more effective at improving vision
- 22. Recommendations • If Bevacizumab (& Ranibizumab / Aflibercept are not affordable) is available appropriately compounded it should be used for eyes with good VA • For eyes with poor VA at presentation Aflibercept is preferred
- 23. Variabilty
- 24. Discussion • Bevacizumab used in trials (CATT, IVAN, Protocol T) – is Avastin + • Same preparation not available to most ophthalmologists
- 25. Similar VA gains in overall population between aflibercept and ranibizumab at 2 years Meanchangefrombaselinein visualacuityletterscore 25 20 25 10 5 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 68 84 104 Aflibercept Bevacizumab Ranibizumab Week +12.8 +12.3 +10.0 At Year 1, the improvement was greater, but not clinically meaningful, with aflibercept than with the other two drugs.1 At Year 2, the difference in VA gain between aflibercept and ranibizumab was no longer significant (p = 0.47), indicating that a dose of ranibizumab that is 60% of the 0.5 mg ex-U.S. approved dose produced equivalent VA gains over 2 years to the full aflibercept 2.0 mg dose.2 1. Wells JA, et al. NEJM 2015;372:1193-203; 2. Wells JA, et al. . Ophthalmology 2016;XX:1-9 http://dx.doi.org/10.1016/j.ophtha.2016.02.022 +13.5 +11.5 +10.0
- 26. No significant difference in the proportion of patients with ≥10- or ≥ 15-letter gains between aflibercept and ranibizumab at 2 years 0 10 20 30 40 50 60 70 ≥10-letter gain ≥15-letter gain ≥10-letter loss ≥15-letter loss Proportionofpatients(%) Aflibercept (n = 201) Bevacizumab (n = 185) Ranibizumab (n = 191) p = 0.22 p = 0.50 p = 0.51 p = 0.49 p = 0.15 p = 0.39 p = 0.70 p = 0.70 p = 0.70 p = 0.84 p = 0.84 p = 0.84 There were no significant differences in the proportion of patients that had a ≥10 or ≥15-letter improvement or worsening Proportion of patients with ≥10- or ≥15-letter gain or loss Wells JA, et al. . Ophthalmology 2016;XX:1-9 http://dx.doi.org/10.1016/j.ophtha.2016.02.022
- 27. No difference in injection frequency over 2 years across the three treatment arms Aflibercept Bevacizumab Ranibizumab p value aflibercept– ranibizumab Total no. of injections in Year 11* (maximum = 13) N = 208 N = 206 N = 206† Mean (standard deviation) 9.2 (2.0) 9.7 (2.3) 9.4 (2.1) Median (25th, 75th percentile) 9 (8, 11) 10 (8, 12) 10 (8, 11) 0.19‡ Total no. of injections in Year 22 N = 201 N = 185 N = 192** Mean (standard deviation) 5.0 (3.4) 5.5 (3.9) 5.4 (3.8) Median (25th, 75th percentile) 5 (2, 7) 6 (2, 9) 6 (2, 9) 0.32§ Total no. of injections over 2 years2 N = 201 N = 185 N = 192**¶ Mean (standard deviation) 14.2 (4.6) 15.3 (5.3) 14.8 (5.0) Median (25th, 75th percentile) 15 (11, 17) 16 (12, 20) 15 (11, 19) 0.08§ See notes for table key and footnotes 1. Wells JA, et al. NEJM 2015;372:1193-203; 2. Wells JA, et al. . Ophthalmology 2016;XX:1-9 http://dx.doi.org/10.1016/j.ophtha.2016.02.022
- 28. Percentage of laser treatments over 2 years Aflibercept Bevacizumab Ranibizumab p value aflibercept– ranibizumab N = 208 N = 206 N = 206† At least one focal/grid photocoagulation laser treatment between 24 weeks and 1 year1*, % 37% 56% 46% 0.058‡ N = 201 N = 185 N = 192 At least one focal/grid photocoagulation laser treatment in Year 22, % 20% 31% 27% 0.12§ At least one focal/grid photocoagulation laser treatment over 2 years2, % 41% 64% 52% 0.04¶ See notes for table key and footnotes 1. Wells JA, et al. NEJM 2015;372:1193-203; 2. Wells JA, et al. . Ophthalmology 2016;XX:1-9 http://dx.doi.org/10.1016/j.ophtha.2016.02.022
- 29. ≥15 Letter Improvement at 2 Years Baseline Visual Acuity 20/32 to 20/40 29 20% 17% 19% Percent Observed Data Treatment Group Comparisons* Adjusted Difference CI P- Value Aflibercept vs Bevacizumab +1% -10% to +11% 0.89 Aflibercept vs Ranibizumab +2% -8% to +11% 0.89 Ranibizumab vs Bevacizumab -1% -11% to +10% 0.89 * P-values adjusted for baseline visual acuity and multiple comparisons
- 30. ≥10 Letter Worsening at 2 Years Baseline Visual Acuity 20/32 to 20/40 30 4% 4% 1% Percent Observed Data Treatment Group Comparisons* Adjusted Difference CI P- Value Aflibercept vs Bevacizumab 0 -6% to +5% 0.96 Aflibercept vs Ranibizumab +3% -3% to +8% 0.55 Ranibizumab vs Bevacizumab -3% -8% to +3% 0.55 * P-values adjusted for baseline visual acuity and multiple comparisons
- 31. ≥10 Letter Improvement at 2 Years Baseline Visual Acuity 20/50 or worse 31 76% 66% 71% Percent Observed Data Treatment Group Comparisons* Adjusted Difference CI P- Value Aflibercept vs Bevacizumab +10% -6% to +26% 0.35 Aflibercept vs Ranibizumab +3% -9% to +15% 0.57 Ranibizumab vs Bevacizumab +7% -6% to +20% 0.57 * P-values adjusted for baseline visual acuity and multiple comparisons
- 32. ≥15 Letter Improvement at 2 Years Baseline Visual Acuity 20/50 or worse 32 58% 52% 55% Percent Observed Data Treatment Group Comparisons* Adjusted Difference CI P- Value Aflibercept vs Bevacizumab +8% -9% to +25% 0.74 Aflibercept vs Ranibizumab +2% -11% to +15% 0.75 Ranibizumab vs Bevacizumab +6% -8% to +20% 0.75 * P-values adjusted for baseline visual acuity and multiple comparisons
- 33. ≥10 Letter Worsening at 2 Years Baseline Visual Acuity 20/50 or worse 33 5% 9% 2% Percent Observed Data Treatment Group Comparisons* Adjusted Difference CI P- Value Aflibercept vs Bevacizumab -3% -10% to +3% 0.49 Aflibercept vs Ranibizumab +2% -3% to +7% 0.49 Ranibizumab vs Bevacizumab -5% -13% to +3% 0.33 * P-values adjusted for baseline visual acuity and multiple comparisons
- 34. Safety • Systemic APTC rates were higher in the ranibizumab group, with a greater number of nonfatal strokes and vascular deaths in the ranibizumab group – Once adjusted for baseline characteristics, the p-values shifted from p=0.047 to p=0.09 for aflibercept versus ranibizumab – These findings are not consistent with previously reported clinical trials.
- 35. Summary Y2 Protocol T • Differences in VA gains observed at 1 year in the overall population and the subgroup of patients treated with ranibizumab or aflibercept with worse baseline BCVA were no longer statistically significant at 2 years • The mean/median number of injections was similar of aflibercept (14.2/15) and ranibizumab (14.8/15).
- 36. Thank You Somdutt PrasadKolkata +917044067754 www.somduttprasad.com