Efficacy of Adalimumab (Humira®) in Spondyloarthritis Related to Crohn's Disease
Overview
- Phase
- Phase 4
- Intervention
- Not specified
- Conditions
- Spondyloarthritis
- Sponsor
- University of Alberta
- Locations
- 1
- Primary Endpoint
- The primary efficacy outcome measure will be the Ankylosing Spondylitis Assessment Study group 20 (ASAS 20) response at 24 weeks.
- Status
- Withdrawn
- Last Updated
- 9 years ago
Overview
Brief Summary
Adalimumab is an antibody treatment that targets and neutralizes a molecule produced in the body that is associated with inflammation, tumor necrosis factor (TNF). This molecule is an important factor in causing the inflammation seen in people with a form of inflammatory spinal arthritis called spondylitis as well as inflammation in the bowel called Crohn's disease. Spondylitis and Crohn's disease tend to go together and this study will assess to what degree this treatment is effective for those patients that have both disorders at the same time.
Detailed Description
The primary objective of the present study is to assess the efficacy of adalimumab in ameliorating the signs and symptoms of spondyloarthritis associated with CD. Although AS patients with IBD were recruited in phase III trials of anti-TNF therapy and shown to respond to treatment, this has not been established in a cohort of patients with exclusive enteropathic spondyloarthritis. Evaluation of such a cohort will address several important issues: * Firstly, it will answer the question of whether or not patients with enteropathic spondyloarthritis respond to treatment with adalimumab. * Secondly, since patients with IBD represent a cohort at high risk of developing spondyloarthritis, this approach will allow the study of the efficacy of adalimumab in patients with pre-radiographic inflammatory back pain as determined by clinical, laboratory, and radiological outcomes. In particular, the use of MRI as an outcome measure will be explored. In addition, this will allow the further evaluation of diagnostic criteria for pre-radiographic AS. * Thirdly, the efficacy of adalimumab in treating IBD associated with SpA has not been previously determined. It has been assumed that the response should be the same as that observed in idiopathic disease. However, it is important to note that the bowel disease related to spondyloarthritis has different genetic associations from idiopathic disease and may have a different underlying pathophysiology. Several biomarkers have been shown to reflect response to anti-TNF therapies in spondyloarthritis e.g. MMP3 and VEGF. However, other surrogates of disease, such as bowel permeability, have yet to be examined.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is 18 years of age or older
- •Patient has a clinical diagnosis with Crohn's disease, as determined by his/her medical history and confirmation of diagnosis by a gastroenterologist
- •Patient has either moderate to severely active Crohn's disease as defined by a CDAI score of \> 220 and \< 450 at Screening or active inflammatory back pain as defined by a BASDAI ≥ 4
- •Subject has failed to respond to an adequate course, is intolerant to, or has contraindication to eitherach of the following therapies: Corticosteroids (Prednisone/Budesonide),MTX or Azathioprine/6-mercaptopurine
- •Patient is on stable (≥ 1 month) concurrent therapies for Crohn's disease, including 5-aminosalicylates, prednisone (\<20 mg/day), budesonide (\<9 mg/day), azathioprine, 6-mercaptopurine, methotrexate, and antibiotics
- •If female, patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control:condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD),contraceptives (oral or parenteral) for three months (90 days) prior to study drug administration), a vasectomized partner, total abstinence from sexual intercourse
- •If patient is female and of childbearing potential, the results of a serum pregnancy test performed at Screening, prior to the first dose of adalimumab, must be negative
- •Patient has Crohn's disease for at least 4 months
- •Patient has not taken NSAIDs (including OTC) for ≥2 weeks
- •Patient has inflammatory back pain according to the Calin or Rudwaleit criteria
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
The primary efficacy outcome measure will be the Ankylosing Spondylitis Assessment Study group 20 (ASAS 20) response at 24 weeks.
Time Frame: 24 weeks
Secondary Outcomes
- Nocturnal Back Pain(12 and 24 weeks)
- Patient Global Assessment of arthritic and CD-related disease activity(12 and 24 weeks)
- Total Back Pain(12 and 24 weeks)
- Patient Acceptable Symptom State (PASS) assessments(12 and 24 weeks)
- Enthesitis assessment(12 and 24 weeks)
- Bowel permeability(12 and 24 weeks)
- Crohn's Disease Activity Index (CDAI)(12 and 24 weeks)
- ASAS 20 response(12 weeks)
- Bath Ankylosing Spondylitis Functional Index (BASFI)(12 and 24 weeks)
- Helplessness scale(12 and 24 weeks)
- Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index (SPARCC MRI)(24 weeks)
- Spinal mobility assessment(2 and 24 weeks)
- ASAS 40, 50, 70, 5/6 responses(12 and 24 weeks)
- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(12 and 24 weeks)
- Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP)(12 and 24 weeks)
- Short form 36 (SF-36™)(12 and 24 weeks)
- Serum biomarkers matrix metalloproteinase 3 (MMP3), vascular endothelial growth factor (VEGF), DKK-1, Wnt, RANKL, OPG and cytokines (e.g. IL17, IL23, IL18)(12 and 24 weeks)