Simon Krabbe1,2, Mikkel Østergaard3,4, Iris Eshed3,4, Inge J Sørensen3,4, Bente Jensen3,4, Jakob M Møller3,4, Lone Balding3,4, Ole R Madsen3,4, Karsten Asmussen3,4, Grith Eng3,4, Niklas R Jørgensen3,4, Susanne J Pedersen3,4. 1. From the Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, and Department of Clinical Biochemistry, Rigshospitalet, Glostrup; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen; Center for Rheumatology and Spine Diseases, Frederiksberg Hospital, Frederiksberg; Department of Radiology, Copenhagen University Hospital Herlev, Herlev; Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte, Hellerup; Department of Rheumatology, Zealand University Hospital, Køge; Odense Patient Data Explorative Network (OPEN), Odense University Hospital/Institute of Clinical Research, Odense, Denmark; Department of Diagnostic Imaging, Sheba Medical Center (affiliated with the Sackler School of Medicine, Tel Aviv University), Ramat Gan, Israel. simonkrabbe@gmail.com. 2. S. Krabbe, MD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; M. Østergaard, MD, PhD, DMSc, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; I. Eshed, MD, Department of Diagnostic Imaging, Sheba Medical Center; I.J. Sørensen, MD, PhD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; B. Jensen, MD, Center for Rheumatology and Spine Diseases, Frederiksberg Hospital; J.M. Møller, Radiographer, Department of Radiology, Copenhagen University Hospital Herlev; L. Balding, MD, Department of Radiology, Copenhagen University Hospital Herlev; O.R. Madsen, MD, PhD, DMSc, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte; K. Asmussen, MD, PhD, Center for Rheumatology and Spine Diseases, Frederiksberg Hospital; G. Eng, MD, PhD, Department of Rheumatology, Zealand University Hospital Køge; N.R. Jørgensen, MD, PhD, DMSc, Department of Clinical Biochemistry, Rigshospitalet, and OPEN, Odense University Hospital/Institute of Clinical Research; S.J. Pedersen, MD, PhD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte. simonkrabbe@gmail.com. 3. From the Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, and Department of Clinical Biochemistry, Rigshospitalet, Glostrup; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen; Center for Rheumatology and Spine Diseases, Frederiksberg Hospital, Frederiksberg; Department of Radiology, Copenhagen University Hospital Herlev, Herlev; Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte, Hellerup; Department of Rheumatology, Zealand University Hospital, Køge; Odense Patient Data Explorative Network (OPEN), Odense University Hospital/Institute of Clinical Research, Odense, Denmark; Department of Diagnostic Imaging, Sheba Medical Center (affiliated with the Sackler School of Medicine, Tel Aviv University), Ramat Gan, Israel. 4. S. Krabbe, MD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; M. Østergaard, MD, PhD, DMSc, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; I. Eshed, MD, Department of Diagnostic Imaging, Sheba Medical Center; I.J. Sørensen, MD, PhD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; B. Jensen, MD, Center for Rheumatology and Spine Diseases, Frederiksberg Hospital; J.M. Møller, Radiographer, Department of Radiology, Copenhagen University Hospital Herlev; L. Balding, MD, Department of Radiology, Copenhagen University Hospital Herlev; O.R. Madsen, MD, PhD, DMSc, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte; K. Asmussen, MD, PhD, Center for Rheumatology and Spine Diseases, Frederiksberg Hospital; G. Eng, MD, PhD, Department of Rheumatology, Zealand University Hospital Køge; N.R. Jørgensen, MD, PhD, DMSc, Department of Clinical Biochemistry, Rigshospitalet, and OPEN, Odense University Hospital/Institute of Clinical Research; S.J. Pedersen, MD, PhD, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, and Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Gentofte.
Abstract
OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA). METHODS: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6. RESULTS: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients. CONCLUSION:ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.
RCT Entities:
OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA). METHODS: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6. RESULTS: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients. CONCLUSION:ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.
Entities:
Keywords:
INFLAMMATION; MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; SPONDYLOARTHRITIS; WHOLE-BODY IMAGING
Authors: Susanne J Pedersen; Mikkel Østergaard; Simon Krabbe; Inge J Sørensen; Bente Jensen; Jakob M Møller; Lone Balding; Ole R Madsen; Robert G W Lambert; Walter P Maksymowych Journal: RMD Open Date: 2018-03-16