Compositions and methods for treating inflammatory bowel disease using a combination therapy of small molecule inhibitors of C-C chemokine receptor type 9 (CCR9) and anti-α4β7 integrin blocking antibodies
Provided herein are compositions, methods and kits for treating inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis in a mammal in need thereof. The method include administering to a subject with IBD a combination therapy containing a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-α4β7 integrin antibody such as vedolizumab. Also provided herein is a kit containing the CCR9 inhibitor compound and anti-α4β7 integrin antibody.
1. A method of treating or reducing the development of inflammatory bowel disease in a mammal, comprising: administering a suitable amount of a CCR9 chemokine receptor inhibitor with an anti-α4β7 integrin blocking antibody, wherein the CCR9 chemokine receptor inhibitor is vercirnon, wherein the anti-α4β7 integrin blocking antibody is vedolizumab.
2. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease (CD) or ulcerative colitis (UC).
3. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease (CD).
4. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis (UC).
5. The method of claim 1 , wherein the CCR9 chemokine receptor inhibitor and the anti-α4β7 integrin blocking antibody are administered in a combination formulation.
6. The method of claim 1 , wherein the CCR9 chemokine receptor inhibitor and the anti-α4β7 integrin blocking antibody are administered sequentially.
7. The method of claim 6 , wherein the CCR9 chemokine receptor inhibitor is administered prior to or after the anti-α4β7 integrin blocking antibody.
8. The method of claim 6 , wherein the CCR9 chemokine receptor inhibitor is administered after administration of the anti-α4β7 integrin blocking antibody.
9. The method of claim 1 , further comprising administering one or more additional active ingredients selected from anti-inflammatory compounds and antibiotics.
10. The method of claim 1 , wherein a weight ratio of the CCR9 inhibitor to the anti-α4β7 integrin antibody is from about 1000:1 to about 1:1000.
11. The method of claim 1 , wherein the suitable amount of anti-α4β7 integrin antibody is from about 0.1 mg/kg, about 10 mg/kg.
12. The method of claim 1 , wherein the suitable amount of anti-α4β7 integrin antibody is sufficient to achieve about 1 μg/ml to about 25 μg/ml mean steady state trough serum concentration of anti-α4β7 integrin antibody during a maintenance phase of treatment.
13. The method of claim 1 , wherein the CCR9 inhibitor is administered once or twice per day.
14. The method of claim 1 , wherein the CCR9 inhibitor is provided in the form of tablets containing 1.0 to 1000 milligrams of the CCR9 inhibitor.
15. The method of claim 1 , wherein the suitable amount of CCR9 inhibitor is about 0.001 to 100 mg per kg patient body weight per day.
16. The method of claim 1 , wherein the anti-α4β7 integrin antibody is a liquid formulation.
17. The method of claim 16 , wherein the liquid formulation comprises the anti-α4β7 integrin antibody, a buffering agent, a non-reducing sugar, and a free amino acid.
18. The method of claim 17 , wherein the liquid formulation further comprises an antioxidant or chelator.