Methods of treating a patient having an autoimmune disorder by administering a soluble BCMA
View Patent ↗Therapeutic regimens for administration of BAFF antagonists for treatment of immunologic and related disorders are described. Regimens involve a short-term BAFF antagonist administration course followed by an extended no-treatment period prior the round of administration.
1. A method of treating a patient having an autoimmune disorder, comprising:
(a) administering to the patient a therapeutically effective amount of a soluble BCMA (B cell maturation antigen) polypeptide at least once or at one or more intervals of less than N weeks;
(b) temporarily discontinuing the administration of step (a) for N weeks or longer; and
(c) repeating steps (a) and (b) at least once;
wherein N is 8, 9, 10, 11, or 12.
2. The method of claim 1 , wherein the administration of step (a) comprises an interval of 1, 2, 3, 4, 5, 6, or 7 weeks.
3. The method of claim 1 , wherein the soluble BCMA polypeptide is administered in step (a) 2, 3, 4, 5, 6, or 7 times a week.
4. The method of claim 1 , wherein the administration is discontinued in step (b) for 12, 18, 24, 30, 36, 42, 48 weeks or longer.
5. The method of claim 1 , wherein at the beginning of the treatment the patient has one or more of:
(i) proteinuria of 1 g per a 24-hour period or higher;
(ii) serum creatinine levels of about 1 mg/dl or higher;
(iii) creatinine clearance levels of 97 ml/min or lower;
(iv) blood urea of 20 mg/dl or higher;
(v) abnormal titer of autoantibodies in the serum; and
(vi) peripheral blood B cell count of 700 cells/μl.
6. The method of claim 5 , wherein the patient is human.
7. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to inhibit autoantibody titer.
8. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to reduce B cell hyperplasia.
9. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to reduce cardiac inflammation.
10. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to improve renal function.
11. The method of claim 10 , wherein the renal function is one or more of: pressure filtration, selective reabsorption, tubular secretion, and systemic blood pressure regulation.
12. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to reduce progression of renal fibrosis.
13. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to reduce lymphocyte infiltration in the kidneys.
14. The method of claim 1 , wherein the therapeutically effective amount of the soluble BCMA polypeptide is sufficient to reduce lymphadenopathy.
15. The method of claim 1 , wherein the autoimmune disorder is systemic lupus erythematosus.
16. The method of claim 1 , wherein the soluble BCMA polypeptide is fused to a constant region of an immunoglobulin.
17. The method of claim 16 , wherein the immunoglobulin is IgG 1 or IgG 4 .
18. The method of claim 16 , wherein the constant region of an immunoglobulin comprises an Fc portion.
19. A method of reducing autoantibody titer in a patient in need thereof, comprising:
(a) administering to the patient a therapeutically effective amount of a soluble BCMA (B cell maturation antigen) polypeptide at least once or at one or more intervals of less than N weeks;
(b) temporarily discontinuing the administration of step (a) for N weeks or longer; and
(c) repeating steps (a) and (b) at least once;
thereby reducing autoantibody titer, and wherein N is 8, 9, 10, 11, or 12.
20. A method of inhibiting generation of pathogenic B cells in a patient in need thereof, comprising:
(a) administering to the patient a therapeutically effective amount of a soluble BCMA (B cell maturation antigen) polypeptide at least once or at one or more intervals of less than N weeks;
(b) temporarily discontinuing the administration of step (a) for N weeks or longer; and
(c) repeating steps (a) and (b) at least once;
thereby inhibiting generation of pathogenic B cells, and wherein N is 8, 9, 10, 11, or 12.
21. The method of claim 20 , wherein the pathogenic B cells are IgM − IgD + .