The SPECTRA Collaboration
(Study grouP for x-trEme Computed Tomography in Rheumatoid Arthritis)
Clinical trials in inflammatory arthritis are designed to determine whether a new therapeutic approach is successful at both improving symptoms and inhibiting joint damage progression, since this is associated with longterm functional outcomes. It is difficult to interpret the significance of structural outcomes in modern trials given that the accepted outcome measure, plain radiography, is limited in the detection of change. Despite great bone resolution, plain radiography only provides a 2D evaluation of a 3D surface, resulting in errors related to positioning and overlapping bony interfaces in particular views. As well, modern clinical trials have short duration placebo phases, making change difficult to detect with the focus on early diagnosis and treat-to-target, patients are enrolled with low levels of damage at baseline and with little progression expected in either treatment group.
Finally, current radiographic scoring schemes are based on ordinal scoring of joint space width and erosions, and cannot detect small and important changes in these parameters, nor of changes in periarticular bone density, which is an important indicator of active inflammation of the peripheral joints.
More sensitive and specific imaging biomarkers would be of great utility to improve radiographic progression determination in clinical trials. Thus, new modalities which could improve the detection of pre-erosive bony changes and provide quantitative measurements of bone densitometry and microarchitecture would be of value in clinical trials. The SPECTRA Collaboration was formed in 2011 to establish the validity, reliability, and responsiveness of a newly available imaging modality, high-resolution peripheral quantitative computed tomography (HR-pQCT), as a biomarker for joint damage in inflammatory arthritis.
This instrument was originally designed to measure cortical and trabecular bone density and bone microarchitecture in 3D at the peripheral limbs. There are many advantages to this novel technology driving this work. With an isotropic voxel size of 82 µm, HR-pQCT allows for meticulous detection of periarticular bone damage such as erosions, cysts, joint space narrowing and bone proliferations in inflammatory and degenerative disease. The quantitative nature of the technology allows calculation of periarticular bone density and microarchitecture with excellent reproducibility, as well as joint space width. Moreover, it is safe with a very low irradiation dose (5µSv to image a 0.9 cm region of interest) and the scanning protocols are well-tolerated by patients with active inflammation.
Dr. Cheryl Barnabe, MD MSc FRCPC, Assistant Professor, Departments of Medicine and Community Health Sciences, University of Calgary, CANADA
Dr. Barnabe is an Assistant Professor in the Departments of Medicine and Community Health Sciences at the University of Calgary. Her HR-pQCT research foci are to characterize periarticular bone and joint space changes in early Rheumatoid Arthritis and Undifferentiated Arthritis, as well as determining what effect biologic therapies have on joint structure. This work is supported by an operating grant from The Arthritis Society.
Dr. Stephanie Finzel, MD, Department of Rheumatology, University Clinic of Erlangen, University of Erlangen-Nuremburg, GERMANY
Dr. Stephanie Finzel studied medicine at the Friedrich-Alexander-University of Erlangen-Nuremberg in Germany. She is currently working as an MD in the Department of Internal Medicine 3, Rheumatology and Immunology, at the University Clinic of Erlangen. Her main focus is the detection of periarticular bone changes in early and established inflammatory arthritis via musculoskeletal ultrasound (MSUS) and high-resolution peripheral quantitative computed tomography (HR-pQCT).
Stephanie was a fellow for the OMERACT ultrasound workshop in 2012 and is now an established member of the ultrasound workshop.
Her aim is to support the validation process of both imaging techniques as outcome parameters in rheumatology clinical trials according to the methodology and regularities of OMERACT.
Dr. Kathryn Stok, PhD, Senior Research Associate, ETH Zurich, SWITZERLAND
Dr. Kathryn Stok, PhD, Senior Research Associate, ETH Zurich, SWITZERLAND Dr. Stok is an innovative biomedical engineer in microstructural imaging and biomechanics of cartilage and joint structures using a variety of experimental and computational approaches. Her research work merges solid engineering approaches with biological advancement. Recently, she has established a novel quantitative imaging approach for cartilage and joint structures using computed tomography, thereby uncovering new information on the progressive destruction of arthritis and similar diseases.