Denosumab, a fully human monoclonal antibody to RANKL was approved for the treatment of postmenopausal osteoporosis in June 2010. It is administered subcutaneously once every 6 months and is highly effective in reducing the risk of vertebral, non-vertebral, and hip fracture risk. There are 3 main concepts underpinning the rationale for using Denosumab to treat CD. 1. CD is associated with an increased risk for osteoporosis and the biology of osteoporosis and T cell mediated inflammation, thought to be integral in CD, involve the RANKL paradigm 2. Animal models of bone loss and colitis treated with RANKL inhibitors improve both bone mass and colitis. A dinitrofluorobenzene sulfonic acid (DNBS) model of colitis in our lab showed significant improvement with Denosumab treatment compared to vehicle (saline) treatment. 3. CD is associated with an increase in mutations at the locus that encodes for RANKL The investigators are conducting an open label pilot study of single dose Denosumab 120 mg s.c. to patients with active Crohn's disease, with assessment of clinical response and remission at 12 weeks.
Name: DenosumabDescription: Single dose subcutaneous administrationType: Drug
Single arm single dose of denosumab
Description: A drop in CDAI of 100 pointsMeasure: Disease Response Time: week 12
Description: Decrease in CDAI to ≤150 points at 12 weeks.Measure: Disease Remission Time: week 12
Description: In those with elevated fecal calprotectin at baseline, reduction in fecal calprotectin to <250 ug/g at week 12.Measure: fecal calprotectin decrease Time: week 12
Description: for those with increased CRP at baseline change in CRP to normal at week 12Measure: CRP decrease Time: week 12
Description: For those who underwent endoscopy within 1 month of study enrollment as part of standard of care and who underwent a repeat endoscopy within 1 month of study completion as part of standard of care, improvement in endoscopy by Crohn's Disease Endoscopy Inflammation Score (CDEIS) between baseline and second endoscopy.Measure: Endoscopy score decrease Time: week 12
Description: For those who underwent abdominal MRI within 1 month of study enrollment as part of standard of care and who underwent a repeat abdominal MRI within 1 month of study completion as part of standard of care then improvement in MRI findings by central reader (Dr H Greenberg) between baseline and second abdominal MRI.Measure: MRI improvement Time: week 12
Description: Serum calcium will be assessed at 3 days post drug administration and every 4 weeks. There is a rare incidence of hypocalcemia with use of this drug. Osteonecrosis of the jaw will be assessed at every study visit. This drug is rarely associated with this outcome especially in cancer patients. Liver enzymes every 4 weeks will be assessed.Measure: Safety will be assessed for any unforeseen adverse events at each study visit Time: week 12
Single Group Assignment
There is one SNP
5. Patients must carry at least one G allele at rs2062305.