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Gary Sternberg, Kha Le, Eric Wakshull, Jeriza Rusit, Jennifer Visich, Jeffrey Nau; Analysis of 24 month data from the HARBOR study indicates that anti-therapeutic antibodies status had no significant impact on the treatment response to ranibizumab. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3793.
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To study the relationship between treatment response and presence of anti-therapeutic antibody (ATA) at Month 12 and 24 following repeated intravitreal (IVT) ranibizumab (RBZ) administration in patients with neovascular age-related macular degeneration (AMD) in the HARBOR study.
This sub-analysis included patients with wet AMD (n=1095) randomized 1:1:1:1 to receive IVT injections of RBZ 0.5 mg or 2.0 mg monthly or pro-re-nata (PRN) dosing following 3 monthly loading doses. Serum samples to measure RBZ concentrations were collected at screening, days 3, 7, 14 , 90, 97 and months 12 and 24. Serum samples for the evaluation of immunoreactivity to RBZ were collected at screening and at months 6, 12, and 24. Treatment response was assessed using best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) imaging at days 7, 30 and at monthly intervals afterwards. Serum RBZ concentrations were determined using a ligand-capture method. Serum ATA to RBZ was detected using a bridging ELISA.
The percentages of patients treated monthly that were ATA positive were 12.4% (2mg) vs 7.5% (0.5mg) at month 12 and 16.2% (2mg) vs. 9.4% (0.5mg) at month 24. Among PRN patients the percentages were 12% (2mg) vs. 8% (0.5mg) at month 12 and 14.2 %(2mg) vs. 8.4% (0.5mg) at month 24. Positive ATA status did not correlate with a change in serum RBZ concentrations, change in BCVA or change in central foveal thickness (CFT) in any treatment groups. Furthermore, there were no differences in the relationship between RBZ serum concentration and CFT and VA in ATA-positive versus ATA negative patients. The percent of patients that were ATA positive at month 24 was slightly higher than at month 12 (increase < 4%). However, patients with positive ATA at month 12 did not have increased antibody titers, nor worsening treatment response at month 24.
This is the most comprehensive analysis of the relationship between ATA status, pharmacokinetics and pharmacodynamics (VA and CFT) in a large group of AMD patients receiving RBZ 0.5 mg or 2.0 mg as monthly or PRN regimen for 12 or 24 months. Following repeated IVT administration for up to 2 years, the ATA status did not appear to alter pharmacokinetics, pharmacodynamics, or treatment efficacy of ranibizumab in AMD.
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