Clinical Studies:
Trex-AMD
Citations:
One-year Results: Wykoff CC, Croft DE, Brown DM, Wang R, Payne JF, Clark L, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: TREX-AMD 1-Year Results. Ophthalmology. 2015 Dec;122(12):2514-22.
Two-year Results: Wykoff CC, Ou WC, Brown DM, Croft DE, Wang R, Payne JF, Clark WL, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Randomized Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: 2-Year Results of the TREX-AMD Study. Ophthalmol Retina. 2017 Jul-Aug;1(4):314-321.
Three-year Results: Wykoff CC, Ou WC, Croft DE, Payne JF, Brown DM, Clark WL, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial. Br J Ophthalmol. 2018 Apr;102(4):460-464.
Key Points
- Primary Study: The TREX-AMD trial was a Phase IIIb multicenter, randomized, treatment-controlled trial that compared “monthly” ranibizumab 0.5mg for 100 weeks then PRN for 56 weeks compared with “treat and extend” ranibizumab 0.5mg for 156 weeks.
- At 1 year there was no significant difference in letters gained between monthly and treat and extend cohorts (9.2 and 10.5, respectively), with an expected difference in the mean number of injections administered (13.0 and 10.1, respectively).
- At 2 years there was again no significant difference in letters gained between monthly and treat and extend cohorts (10.5 and 8.7, respectively), though a higher percentage of patients in the treat and extend cohort did lose letters (no monthly patients lost more than 2 letters, while 13% of treat and extend patients lost more than 15 letters).
- At 3 years, with conversion to PRN dosing the monthly dosing cohort had decline in BCVA (from +10.5 through year 2 to +5.4 in year 3). Similar BCVA between the treatment arms (+5.4 and +5.0).
-
Objective
To prospectively assess a treat-and-extend management strategy compared with fixed monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration patients
-
STUDY DESIGN
Phase 3b, multicenter, randomized, treatment-controlled trial
-
DURATION
36 months primary study, with intervals at 12 and 24 months
STUDY SUBJECTS
Major inclusion criteria:
- Adults (age >50), with any CNVM lesion (occult, minimally classic, or classic; leakage on fluorescein angiography or subretinal, intraretinal activity on SDOCT) secondary to age-related macular degeneration
- ETDRS best corrected visual acuity (BCVA) of 20/32 to 20/400 in the study eye
Major exclusion criteria:
- Total area of subretinal hemorrhage or fibrosis >50% of the entire lesion
- Any prior treatment with anti-VEGF agents in the study eye
- Poor media preventing imaging, or poor pupil dilation
- Total lesion size >1 dd
- Subretinal hemorrhage in the study eye that involves the fovea
- Subfoveal fibrosis or atrophy in the study eye
- CNVM in either eye due to other causes such as ocular histoplasmosis, trauma, or myopia
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:2 to
- (a) ranibizumab 0.5mg injection fixed monthly for 2 years then monthly PRN
- (b) ranibizumab 0.5mg treat and extend (fixed for 3 months, then if clinically and tomographically inactive extend by 2 week periods)
RESULTS
Study population
- 60 subjects randomized
- 12 month study completion 57
- 24 month study completion 50
- 36 month study completion 46
Visual acuity end-points
- Mean letter gain at one year: monthly +9.2, treat and extend +10.5, no significant difference
- Mean letter gain at two years: monthly +10.5, treat and extend +8.7, no significant difference
- Mean letter gain at three years: monthly (prn) +5.4, treat and extend +5.0, no significant difference
Treatment Burden
- One year: 13.0 monthly versus 10.1 treat and extend
- Two year: 25.5 monthly versus 18.6 treat and extend
- In year three: patients in treat and extend who were transitioned to PRN (after reaching 12 week intervals), the need for further treatment was low (4% of all visits requiring injections)
Anatomic end-points on OCT
- One year: CRT average 271 monthly versus 290 treat and extend, no significant difference
- Two year: CRT decrease -170 monthly versus -170 treat and extend, no significant difference
Adverse events
- No new safety profiles identified for injections across all 3 years of the study, no cases of endophthalmitis or intraocular inflammation amongst 1456 injections
CONCLUSIONS
- Treat and extend dosing provided comparable outcomes in visual acuity outcomes with fewer injections. This was particularly true when treatment in the monthly arm was changed to PRN dosing in year 3.