Methods of treating chronic disorders with complement inhibitors
In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.
1. A method of treating a subject in need of treatment for a chronic respiratory disorder or other chronic complement-mediated disorder, the method comprising administering multiple doses of a complement inhibitor to the subject according to a dosing schedule, wherein successive doses of the complement inhibitor are administered by a respiratory route on average:
(i) between 2 weeks and 6 weeks after the plasma concentration of the complement inhibitor decreases to no more than 20% of the maximum plasma concentration that was reached after the previous dose; or
(ii) between 2 weeks and 6 weeks after plasma complement activation capacity has returned to at least 50% of baseline after the previous dose.
2. A method of treating a subject in need of treatment for a chronic respiratory disorder or other chronic complement-mediated disorder, the method comprising administering multiple doses of a complement inhibitor to the subject according to a dosing schedule,
wherein successive doses of the complement inhibitor are administered by a respiratory route on average at least 2 weeks after the plasma concentration of the complement inhibitor decreases to no more than 20% of the maximum plasma concentration that was reached after the previous dose.
3. The method of claim 1 , wherein at least 5 doses are administered.
4. The method of claim 1 , wherein the subject is in need of treatment for asthma, chronic obstructive pulmonary disease (COPD), or both.
5. The method of claim 1 , wherein the complement inhibitor acts on C3 or upstream of C3 in the complement cascade.
6. The method of claim 1 , wherein the complement inhibitor inhibits cleavage of C3, C5, or factor B.
7. The method of claim 1 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule.
8. The method of claim 7 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule that binds to C3, C5, factor B, or factor D.
9. The method of claim 1 , wherein the complement inhibitor comprises a compstatin analog.
10. The method of claim 2 , wherein at least 5 doses are administered.
11. The method of claim 2 , wherein the subject is in need of treatment for asthma, chronic obstructive pulmonary disease (COPD), or both.
12. The method of claim 2 , wherein the complement inhibitor acts on C3 or upstream of C3 in the complement cascade.
13. The method of claim 2 , wherein the complement inhibitor inhibits cleavage of C3, C5, or factor B.
14. The method of claim 2 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule.
15. The method of claim 14 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule that binds to C3, C5, factor B, or factor D.
16. The method of claim 2 , wherein the complement inhibitor comprises a compstatin analog.
17. A method of treating a subject in need of treatment for a chronic respiratory disorder or other chronic complement-mediated disorder, the method comprising administering multiple doses of a complement inhibitor to the subject according to a dosing schedule in which successive doses are administered by a respiratory route on average:
(i) at least 2 weeks after the plasma concentration of the complement inhibitor decreases to no more than 20% of the maximum plasma concentration that was reached after the previous dose;
(ii) at least 2 weeks after plasma complement activation capacity has returned to at least 50% of baseline after the previous dose; or
(iii) at least 2 weeks after the plasma concentration of the complement inhibitor decreases to no more than 1% of the maximum plasma concentration that was reached after the previous dose.
18. The method of claim 17 , wherein at least 5 doses are administered.
19. The method of claim 17 , wherein the subject is in need of treatment for asthma, chronic obstructive pulmonary disease (COPD), or both.
20. The method of claim 17 , wherein the complement inhibitor acts on C3 or upstream of C3 in the complement cascade.
21. The method of claim 17 , wherein the complement inhibitor inhibits cleavage of C3, C5, or factor B.
22. The method of claim 17 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule.
23. The method of claim 22 , wherein the complement inhibitor comprises an antibody, aptamer, peptide, polypeptide, or small molecule that binds to C3, C5, factor B, or factor D.
24. The method of claim 17 , wherein the complement inhibitor comprises a compstatin analog.