Methods of improving retina-associated disease outcome using CCR3-inhibitors
The disclosure provides a method of reducing the frequency of administration of an anti-VEGF agent to a subject diagnosed with wet age-related macular degeneration. The method comprises administering a CCR3 inhibitory agent to the subject; administering the anti-VEGF agent to the subject after the administering of the CCR3 inhibitory agent; and administering additional subsequent doses of the anti-VEGF agent to the subject at a frequency less than the recommended frequency. The disclosure further provides a method of treating a subject suffering from a retina-associated disease, the method comprising administering an anti-VEGF agent to a subject suffering from a retina-associated disease and previously treated with a CCR3 inhibitory agent, wherein the anti-VEGF agent is administered at a frequency less than the recommended frequency for the anti-VEGF agent.
1 . A method of reducing the frequency of administration of an anti-VEGF agent to a subject diagnosed with wet age-related macular degeneration, the method comprising: administering a CCR3 inhibitory agent to the subject; administering the anti-VEGF agent to the subject after the administering of the CCR3 inhibitory agent; and administering additional subsequent doses of the anti-VEGF agent to the subject at a frequency less than the recommended frequency, wherein the subject is refractory to the anti-VEGF agent; wherein the CCR3 inhibitory agent is represented by the compound 1,
administered orally, wherein the anti-VEGF is selected from the group consisting of aflibercept, ranibizumab, and bevacizumab, and is administered intravitreally.
2 . The method of claim 1 wherein the frequency less than the recommended frequency is less than seven doses every twelve months.
3 . The method of claim 1 wherein the administering of an anti-VEGF agent to a subject is performed intravitreally.
4 . A method of reducing the frequency of administration of an anti-VEGF agent to a subject diagnosed with wet age-related macular degeneration, the method comprising: administering a CCR3 inhibitory agent to the subject; administering the anti-VEGF agent to the subject after the administering of the CCR3 inhibitory agent; administering additional subsequent doses of the anti-VEGF agent to the subject at a frequency less than the recommended frequency; and determining whether to administer the additional subsequent doses of the anti-VEGF agent by diagnosing a morphological change in an eye of the subject diagnosed with wet age-related macular degeneration, wherein the subject is refractory to the anti-VEGF agent and the morphological change is selected from clinically relevant increased intraretinal fluid, clinical-relevant increased intraretinal fluid, clinically relevant increased choroidal neovascularization, and clinically relevant increased central retinal pigmental epithelium detachment height; wherein the CCR3 inhibitory agent is represented by the compound 1,
administered orally, wherein the anti-VEGF is selected from the group consisting of aflibercept, ranibizumab, and bevacizumab, and is administered intravitreally.
5 . The method of claim 1 wherein the administering the anti-VEGF agent to the subject after the administering of the CCR3 inhibitory agent commences with administration of a loading dose of the anti-VEGF agent.
6 . A method of treating a subject suffering from a retina-associated disease, the method comprising administering an anti-VEGF agent to a subject suffering from a retina-associated disease and previously treated with a CCR3 inhibitory agent, wherein the anti-VEGF agent is administered at a frequency less than the recommended frequency for the anti-VEGF agent and the subject is refractory to the anti-VEGF agent; wherein the CCR3 inhibitory agent is represented by the compound 1,
administered orally, wherein the anti-VEGF is selected from the group consisting of aflibercept, ranibizumab, and bevacizumab, and is administered intravitreally.
7 . The method of claim 6 wherein the subject was treated with the CCR3 inhibitory agent within six months of administration of the anti-VEGF agent.
8 . The method of claim 6 wherein the frequency less than the recommended frequency is less than seven doses every twelve months.
9 . The method of claim 6 wherein the administering of an anti-VEGF agent to a subject is performed intravitreally.