Ignite Creation Date:
2024-05-05 @ 4:42 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00298012
Status:
WITHDRAWN
Last Update Posted:
2009-01-05
First Post:
2006-02-28
Brief Title:
Methotrexate in the Treatment of Axial Spondyloarthritis
Sponsor:
Rheumatism Foundation Hospital
Organization:
Rheumatism Foundation Hospital
Study Overview
Official Title:
Methotrexate in the Treatment of Axial Spondyloarthritis A Randomized Multicenter Double-Blind Placebo-Controlled Study
Status:
WITHDRAWN
Status Verified Date:
2009-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this study is to evaluate the efficacy of oral methotrexate for the treatment of active axial spondyloarthritis early ankylosing spondylitis or spondyloarthritis with sacroiliitis Efficacy will be measured by reduction in the signs and symptoms of active spondyloarthritis including effects on back pain and stiffness range of motion in the spine physical function quality of life and incidence of arthritis enthesitis and anterior uveitis
Detailed Description:
The established classification criteria for ankylosing spondylitis AS rely on the combination of clinical symptoms plus radiographic sacroiliitis of at least grade 2 bilaterally or grade 3 unilaterally It usually takes several years for definite radiographic sacroiliitis to evolve Diagnosis of AS may be delayed up to 10 years after the onset of symptoms if diagnosis is based on the radiographic findings
A group of leading experts in the field of spondyloarthropathies proposed in 2004 the term axial spondyloarthritis as an attempt to narrow the gap of 5-10 years between the first symptoms and the diagnosis of AS Rudwaleit et al Ann Rheum Dis 2004 63535-43 Using the proposed approach an early diagnosis of AS or axial spondyloarthritis can be made with a high degree of confidence when at least two to three spondyloarthritis features clinical findings laboratory tests or skeletal imaging are present Magnetic resonance imaging MRI of the sacroiliac joints appears to be especially useful tool in the diagnosis of early AS Early diagnosis and treatment could probably prevent structural damage and lead to better functional outcomes
Treatment of AS has largely consisted of non-steroidal anti-inflammatory drugs NSAIDs Most disease modifying antirheumatic drugs are not effective in axial manifestations Sulfasalazine has some efficacy on peripheral symptoms Tumor necrosis factor TNF alpha blocking drugs infliximab and etanercept are effective in both axial and peripheral manifestations of the disease According to consensus statement the initiation of anti-TNF alpha therapy requires a definitive diagnosis of AS which is based on radiographic evidence of sacroiliitis
It is well documented that oral methotrexate is effective and safe in the treatment of rheumatoid arthritis and psoriatic arthritis Still studies proving its usefulness for the treatment of AS are lacking To this date three small randomised and controlled trials to clarify this issue have been conducted The dose of methotrexate used in these studies was low only 75 - 10 mg per week One of these studies showed a benefit in the active treatment group There was no statistically significant benefit of methotrexate in the two other studies
The purpose of this study is to assess the efficacy of oral methotrexate in adult subjects with active axial spondyloarthritis Subjects will be randomly assigned to placebo or methotrexate treatment groups All subjects in the active treatment group receive at least a dose of 15 mg per week of oral methotrexate To reduce mucosal gastrointestinal and haematologic side effects of low-dose methotrexate all study subjects receive also a dose of 5 mg per week of folic acid A stable dose of NSAID during the study is permitted The duration of the double-blinded treatment period is 24 weeks
Efficacy of the treatment is measured by reduction in the signs and symptoms of axial spondyloarthritis at weeks 12 and 24 If the primary outcome of ASAS20 ASsessment in Ankylosing Spondylitis response criteria improvement of at least 20 in patient reported symptoms is not met at the week 12 the dose of methotrexate or corresponding placebo will be increased to 20 mg per week during weeks 12 to 24
Clinical history of anterior uveitis and its incidence during the study is also recorded An ophthalmologic examination is performed at baseline and week 24
To a subset of patients a MRI scan of sacroiliac joints will be done also at week 24 to assess changes of active inflammatory lesions as detected by MRI
An extension study of radiological progression is also planned X-ray changes of sacroiliac joints and lumbosacral spine will be assessed at baseline and at 3 and 5 years
A group of leading experts in the field of spondyloarthropathies proposed in 2004 the term axial spondyloarthritis as an attempt to narrow the gap of 5-10 years between the first symptoms and the diagnosis of AS Rudwaleit et al Ann Rheum Dis 2004 63535-43 Using the proposed approach an early diagnosis of AS or axial spondyloarthritis can be made with a high degree of confidence when at least two to three spondyloarthritis features clinical findings laboratory tests or skeletal imaging are present Magnetic resonance imaging MRI of the sacroiliac joints appears to be especially useful tool in the diagnosis of early AS Early diagnosis and treatment could probably prevent structural damage and lead to better functional outcomes
Treatment of AS has largely consisted of non-steroidal anti-inflammatory drugs NSAIDs Most disease modifying antirheumatic drugs are not effective in axial manifestations Sulfasalazine has some efficacy on peripheral symptoms Tumor necrosis factor TNF alpha blocking drugs infliximab and etanercept are effective in both axial and peripheral manifestations of the disease According to consensus statement the initiation of anti-TNF alpha therapy requires a definitive diagnosis of AS which is based on radiographic evidence of sacroiliitis
It is well documented that oral methotrexate is effective and safe in the treatment of rheumatoid arthritis and psoriatic arthritis Still studies proving its usefulness for the treatment of AS are lacking To this date three small randomised and controlled trials to clarify this issue have been conducted The dose of methotrexate used in these studies was low only 75 - 10 mg per week One of these studies showed a benefit in the active treatment group There was no statistically significant benefit of methotrexate in the two other studies
The purpose of this study is to assess the efficacy of oral methotrexate in adult subjects with active axial spondyloarthritis Subjects will be randomly assigned to placebo or methotrexate treatment groups All subjects in the active treatment group receive at least a dose of 15 mg per week of oral methotrexate To reduce mucosal gastrointestinal and haematologic side effects of low-dose methotrexate all study subjects receive also a dose of 5 mg per week of folic acid A stable dose of NSAID during the study is permitted The duration of the double-blinded treatment period is 24 weeks
Efficacy of the treatment is measured by reduction in the signs and symptoms of axial spondyloarthritis at weeks 12 and 24 If the primary outcome of ASAS20 ASsessment in Ankylosing Spondylitis response criteria improvement of at least 20 in patient reported symptoms is not met at the week 12 the dose of methotrexate or corresponding placebo will be increased to 20 mg per week during weeks 12 to 24
Clinical history of anterior uveitis and its incidence during the study is also recorded An ophthalmologic examination is performed at baseline and week 24
To a subset of patients a MRI scan of sacroiliac joints will be done also at week 24 to assess changes of active inflammatory lesions as detected by MRI
An extension study of radiological progression is also planned X-ray changes of sacroiliac joints and lumbosacral spine will be assessed at baseline and at 3 and 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None