Methods of Treating Crohn's Disease with Anti-IL23 Specific Antibody

Abstract

A method of treating Crohn's disease in a patient administers an IL-23 specific antibody, e.g., guselkumab, at an initial intravenous dose and subsequence subcutaneous doses.

What is claimed is: 
     
         1 . A method of treating Crohn's disease in a patient, comprising administering an antibody to IL-23 to the patient, wherein the antibody comprises a light chain variable region and a heavy chain variable region, said light chain variable region comprising:
 a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:50;   a CDRL2 amino acid sequence of SEQ ID NO:56; and   a CDRL3 amino acid sequence of SEQ ID NO:73,   said heavy chain variable region comprising:   a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:5;   a CDRH2 amino acid sequence of SEQ ID NO:20; and   a CDRH3 amino acid sequence of SEQ ID NO:44.   
     
     
         2 . The method of  claim 1 , wherein the antibody is administered in an initial intravenous dose, an intravenous dose 4 weeks after initial treatment, an intravenous dose 8 weeks after initial treatment and a subcutaneous dose every 4 or 8 weeks after the dose at 8 weeks. 
     
     
         3 . The method of  claim 2 , wherein the intravenous dose is selected from the group consisting of 16 mg/kg of the patient, 1200 mg, 600 mg and 200 mg. 
     
     
         4 . The method of  claim 3 , wherein the subcutaneous dose is 100 mg or 200 mg. 
     
     
         5 . The method of  claim 4 , wherein the intravenous dose is 1200 mg and the subcutaneous dose is 200 mg every 4 weeks. 
     
     
         6 . The method of  claim 4 , wherein the intravenous dose is 600 mg and the subcutaneous dose is 200 mg every 4 weeks. 
     
     
         7 . The method of  claim 4 , wherein the intravenous dose is 200 mg and the subcutaneous dose is 100 mg every 8 weeks. 
     
     
         8 . The method of  claim 2 , wherein the patient is a responder to the antibody and is identified as meeting at least one clinical endpoint selected from the group consisting of:
 (i) Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12 The CDAI score will be assessed by collecting information on 8 different Crohn's disease-related variables, with scores ranging from 0 to approximately 600. A decrease over time indicates improvement in disease activity;   (ii) Clinical remission at Week 12, defined as CDAI less than (<) 150 points;   (iii) Clinical response at Week 12, defined as greater than or equal to (>=) 100-point reduction from baseline in CDAI score or CDAI score<150;   (iv) Patient-Reported Outcome (PRO)-2 Remission at Week 12 defined based on average daily stool frequency (SF) and average daily abdominal pain (AP) score;   (v) Clinical-Biomarker Response at Week 12 defined using clinical response based on the CDAI score and reduction from baseline in C-reactive protein (CRP) or fecal calprotectin;   (vi) Endoscopic Response at Week 12 measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD is based on the evaluation of 4 endoscopic components across 5 ileocolonic segments, with a total score ranging from 0 to 56;   (vii) Clinical remission at Week 48 defined as CDAI score<150;   (viii) Durable Clinical Remission at Week 48 defined as CDAI<150 for most of all visits between Week 12 and Week 48;   (ix) Corticosteroid-Free Clinical Remission at Week 48 dfined as CDAI score<150 at Week 48 and not receiving corticosteroids at Week 48;   (x) PRO-2 remission at Week 48 defined based on average daily stool frequency (SF) and average daily abdominal pain (AP) score. Fatigue response at Week 12 based on the Patient-Reported Outcomes Measurement Information System (PROMIS). Fatigue Short Form 7a contains 7 items that evaluate the severity of fatigue, with higher scores indicating greater fatigue; and   (xi) Endoscopic response at Week 48 measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD).   
     
     
         9 . The method of  claim 8 , wherein the clinical endpoint(s) is measured 8, 12, 16, 20, 28, 32, 36, 40, 44 and/or weeks after initial treatment. 
     
     
         10 . The method of  claim 7 , wherein the antibody is in a composition comprising 7.9% (w/v) sucrose, 4.0 mM Histidine, 6.9 mM L-Histidine monohydrochloride monohydrate; 0.053% (w/v) Polysorbate 80 of the pharmaceutical composition; wherein the diluent is water at standard state. 
     
     
         11 . The method of  claim 1 , further comprising administering to the patient one or more additional drugs used to treat Crohn's disease. 
     
     
         12 . The method of  claim 11 , wherein the additional drug is selected from the group consisting of: immunosuppressive agents, non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate (MTX), anti-B-cell surface marker antibodies, anti-CD20 antibodies, rituximab, TNF-inhibitors, corticosteroids, and co-stimulatory modifiers. 
     
     
         13 . The method of  claim 1 , wherein the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 116 and a heavy chain variable region of the amino acid sequence of SEQ ID NO: 106.