Abstract
Purpose :
To determine PK and plasma VEGF evels at baseline, 4 weeks, 6 weeks, or 8 weeks from intravitreal administration of bevacizumab, ranibizumab, or aflibercept and compare them to untreated controls.
Methods :
77 patients, including 8 untreated controls, who were treated with bevacizumab, ranibizumab, or aflibercept at a precedent time interval of 4, 6, or 8 weeks continued to receive the same drug at the same interval and had serum PK and plasma VEGF levels measured at baseline, 4 weeks, and 6 or 8 weeks.
Results :
Untreated controls had little variability in plasma VEGF levels which were almost uniformly <20 pg/ml. (Fig1). Following intravitreal administration of bevacizumab, ranibizumab, or aflibercept as the dosing interval increased there were in general more pronounced decreases of the mean plasma VEGF levels as drug concentration increased, especially in the bevacizumab and aflibercept 6 week and 8 week treatment groups. Mean plasma VEGF levels were less affected by ranibizumab than bevacizumab and aflibercept; the drug concentration effect was most marked in the bevacizumab and aflibercept 6 and 8-week treatment groups. Bevacizumab in the 4-week group induced the lowest mean plasma VEGF levels. Surprisingly many treated patients, as exemplfied in the 4 week groups, at times had much higher plasma VEGF levels (up to 47 pg/ml) than individuals in the control group (Fig. 2). This was also true in the 6 and 8 week groups.
Conclusions :
Aflibercept and bevacizumab, 6 and 8 week groups showed the most pronounced decrement in mean plasma VEGF as drug concentration increased. Paradoxically, plasma VEGF levels were sometimes much higher in treated individuals than in the control group suggesting an attempted homeostatic influence; this is of unknown significance. Perhaps there is up-regulation of systemic VEGF production in response to the anti-VEGF drug challenge. Ranibizumab disturbed mean plasma VEGF levels the least, as did monthly dosing with all agents, and minimizing systemic VEGF disturbances may be beneficial in terms of systemic homeostasis. A more “regular” anti-VEGF drug effect might be more easily compensated than large loads of anti-VEGF that occur irregularly, and theoretically this may have homeostatic benefits both in the eye and systemically.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.