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India ink artifact on Dixon out-of-phase images can be used as a landmark to measure joint space width at MRI. Diagn Interv Imaging 2021; 103:87-96. [PMID: 34666946 DOI: 10.1016/j.diii.2021.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/26/2021] [Accepted: 09/27/2021] [Indexed: 11/23/2022]
Abstract
PURPOSE The purpose of this study was to test the feasibility of joint space width (JSW) measurement on Dixon MR images with the "India ink" artifact between cartilage and bone marrow as a landmark for the subchondral plate and to correlate it with radiographic JSW. MATERIALS AND METHODS Both hands of six volunteers (three women, three men; mean age, 36.7 ± 10.4 [SD] years) and 24 patients with early rheumatoid arthritis (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years) were imaged with MRI Dixon sequences and radiographs. Two radiologists (R1, R2) separately measured JSW in 11 joints per hand on all Dixon images in volunteers, on contrast-enhanced T1-weighted out-of-phase images in patients and on radiographs in both groups. Inter-technique, intra-observer and inter-observer agreements were assessed using intraclass correlation coefficient (ICC) and Bland Altman analysis. RESULTS In volunteers, agreement between JSW measurements on MRI and radiographs was the highest with T1-weighted Dixon out-of-phase images (mean ICC ranging from 0.69 to 0.76 for R1 and 0.65 to 0.74 for R2). In patients, median bias between JSW measurements at first and second readings was not statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of 0.00 and + 0.01 mm) and radiographs (mean bias of 0.00 and +0.01 mm). Median bias of the difference between measurements of R1 and R2 was statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of -0.11 and -0.09 mm; P < 0.039) and radiographs (mean bias of -0.24 and -0.20 mm; P < 0.035). CONCLUSION Measurement of hand JSW on T1-weighted Dixon out-of-phase images using India ink artifact as a landmark for the subchondral plate is repeatable and reproducible.
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Boesen M, Beattie SD, Schlichting DE, Kubassova O. Novel quantitative digital image analysis methodology for assessment of inflammatory changes in MRI data in a post-hoc analysis of data acquired from a phase IIb study of baricitinib in patients with active rheumatoid arthritis. Eur J Radiol 2021; 143:109877. [PMID: 34412009 DOI: 10.1016/j.ejrad.2021.109877] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 07/06/2021] [Accepted: 07/22/2021] [Indexed: 12/26/2022]
Abstract
PURPOSE To evaluate a novel quantitative methodology to assess inflammatory changes in magnetic resonance imaging (MRI) data from patients with rheumatoid arthritis (RA) and the impact of image quality on imaging outcomes compared to the RA Magnetic Resonance Imaging Score (RAMRIS). METHODS Three-dimensional, T1-weighted, fat-suppressed MRI sequences of the hand/wrist before and after intravenous Gadolinium contrast from patients with RA in a placebo-controlled clinical trial (NCT01185353) were re-evaluated post hoc. The methodology was integrated into proprietary software (DYNAMIKA®) and assessed inflammation through pixelated measurements of the contrast-enhancing (inflammatory) volume. A semi-automatic approach outlined contrast-enhancing synovial tissue in the wrist and second to fifth metacarpophalangeal joints with a rough region of interest (ROI); quantitative imaging biomarkers were generated by means of quantitative total volume of inflammation and quantitative degree of inflammation relative to the signal in a 1 cm in diameter ROI in the center of the thenar or lumbrical muscle for internal reference. The time from Gadolinium injection to finalization of the post-contrast images was calculated from the images' Digital Imaging and Communications in Medicine header. An experienced reader graded image quality as poor, acceptable, or good. RESULTS Results from this quantitative methodology, especially when excluding images with poor quality scores (14-32%), provided a more pronounced and monotonically increasing dose-response than the original RAMRIS results on synovitis and osteitis. CONCLUSIONS This computer-aided quantitative scoring method provided continuous measures of inflammatory changes relative to muscle and may be more sensitive and interpretable concerning dose/response separation between RA treatment groups.
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Affiliation(s)
- M Boesen
- Department of Radiology, Copenhagen University Hospital Bispebjerg-Frederiksberg, Copenhagen, Denmark; Image Analysis Group, London, UK.
| | - S D Beattie
- Eli Lilly and Company, Indianapolis, IN, USA
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Abstract
The hand and wrist are commonly involved in rheumatic conditions, particularly rheumatoid arthritis and other systemic connective tissue diseases. With spondyloarthritis, hand and wrist involvement frequently occurs in psoriatic arthritis but generally does not occur in the remaining subtypes. The hand and wrist may also be affected in various metabolic and endocrine diseases, but these lie beyond the scope of this review.Radiographs may demonstrate the presence of joint space narrowing, bone loss, cysts and erosions, malalignments, and osteolysis. They may also show regions of soft tissue swelling or thinning, and detect calcifications. Ultrasonography and magnetic resonance imaging (MRI) enable evaluation of the soft tissues, particularly the synovium, tenosynovium, and tendons. Furthermore, erosions are better demonstrated than on radiographs. MRI allows evaluation of periarticular bone marrow edema.This article discusses typical imaging features of the hand and wrist in rheumatologic conditions including the advantages and limitations of the various methods.
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Minh NN, Nguyen NPT, Ngoc CN, Duy TT, Huy TN, Do BN, Viet TT. Application of ImageJ software for quantification of Hand Joint Space Narrowing in Patients with Rheumatoid Arthritis. Curr Rheumatol Rev 2021; 18:136-143. [PMID: 34080966 DOI: 10.2174/1573397117666210602113848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 02/01/2021] [Accepted: 03/16/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND ImageJ software is used to quantify the joint space width (JSW) of hand and wrist in patients with rheumatoid arthritis (RA) as well as in the healthy control group. METHOD Forty-one RA patients and 31 healthy controls are included in this study. All of 72 participants underwent digital radiography of the bilateral hand and wrist, then all the images were opened by ImageJ software to measure the width of wrist and hand joint space (total 2160 joints). Joint space narrowing (JSN) was defined if the width was less than the mean - 2SD of the control group. RESULT The mean JSW of all sites of wrist and hand joints of RA patients was significantly reduced as compared to those in the control group (p<0.001). There were 37/41 (90.24%) RA patients who had JSN in at least one joint in hand or wrist. In total, 70.89% of joints on the right and 68.46% of joints on the left wrist and hand had JSN. CONCLUSION ImageJ software was simple and convenient , which helps rheumatologists quantify the width of joint space for diagnosis and follow-up in RA patients.
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Affiliation(s)
- Nui Nguyen Minh
- Department of Rheumatology, Military Hospital 103, Hanoi, Vietnam
| | | | - Chau Nguyen Ngoc
- Department of Rheumatology, Military Hospital 103, Hanoi, Vietnam
| | - Tien Tran Duy
- Department of Rheumatology, Military Hospital 103, Hanoi, Vietnam
| | - Thong Nguyen Huy
- Department of Rheumatology, Military Hospital 103, Hanoi, Vietnam
| | - Binh Nhu Do
- Division of Military Science, Military Hospital 103, Hanoi, Vietnam
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Weisel K, Berger S, Thorn K, Taylor PC, Peterfy C, Siddall H, Tompson D, Wang S, Quattrocchi E, Burriss SW, Walter J, Tak PP. A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis. Arthritis Res Ther 2021; 23:85. [PMID: 33726834 PMCID: PMC7962407 DOI: 10.1186/s13075-021-02468-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 02/26/2021] [Indexed: 12/14/2022] Open
Abstract
Background Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of inflammation through cell death and proinflammatory cytokine production. This multicenter, randomized, double-blind (sponsor-unblinded), placebo-controlled, experimental medicine study evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in moderate to severe rheumatoid arthritis (RA). Methods Patients with moderate to severe RA who had received ≥12 weeks’ stable-dose conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy were randomized (2:1) to GSK2982772 60 mg or placebo orally 2 or 3 times daily for 84 days. Safety, PK, disease activity, joint damage, and pharmacodynamic (PD) biomarkers were assessed at days 43 and 85. Results A total of 52 patients were randomized (placebo, 18; GSK2982772, 34). Adverse events (AEs) were reported in 13 (72%) in patients in the placebo group (n = 3 b.i.d; n = 10 t.i.d.) and 20 (61%) in the GSK2982772 group (n = 3 b.i.d; n = 17 t.i.d.). All treatment-related AEs were mild/moderate, except one severe case of alopecia areata at day 49 and retinal vein thrombosis at day 66 (which led to withdrawal from the study) in patients receiving GSK2982772 t.i.d. Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) scores, ACR20/50/70 response, and rates of low disease activity and remission were similar between placebo and GSK2982772 arms. Conclusions These results suggest that inhibition of RIPK1 activity at the GSK2982772 exposure levels evaluated do not translate into meaningful clinical improvement of RA. Trial registration ClinicalTrials.gov Identifier: NCT02858492. Registered 8 August 2016. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02468-0.
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Affiliation(s)
| | | | - Katie Thorn
- GlaxoSmithKline, Stockley Park, Uxbridge, UK
| | - Peter C Taylor
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | | | - Hilary Siddall
- GlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
| | - Debra Tompson
- GlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
| | | | | | | | - Jochen Walter
- Rheumatologische Schwerpunktpraxis, Rendsburg, Germany
| | - Paul Peter Tak
- GlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.,Present address: Cambridge University, Cambridge, UK.,Present address: Ghent University, Ghent, Belgium
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Emery P, Durez P, Hueber AJ, de la Torre I, Larsson E, Holzkämper T, Tanaka Y. Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis-a comprehensive review. Arthritis Res Ther 2021; 23:3. [PMID: 33397481 PMCID: PMC7784289 DOI: 10.1186/s13075-020-02379-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/03/2020] [Indexed: 12/13/2022] Open
Abstract
Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.
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Affiliation(s)
- Paul Emery
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, NIHR Leeds BiomedicalResearch Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
| | - Patrick Durez
- Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Axel J Hueber
- Section Rheumatology, Sozialstiftung Bamberg, Bamberg, Germany
| | | | | | | | - Yoshiya Tanaka
- University of Occupational and Environmental Health, Kitakyushu, Japan
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Ørnbjerg LM, Østergaard M. Assessment of structural damage progression in established rheumatoid arthritis by conventional radiography, computed tomography, and magnetic resonance imaging. Best Pract Res Clin Rheumatol 2020; 33:101481. [PMID: 32001166 DOI: 10.1016/j.berh.2019.101481] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Structural damage progression in patients with established rheumatoid arthritis (RA) has traditionally been assessed by conventional radiography (CR), which has proven its value in clinical practice and clinical trials over the past decades. The most prominent abnormalities visualized by CR in RA patients are erosions as a consequence of bone destruction and joint space narrowing (JSN) as a consequence of cartilage damage. Several validated scoring systems to quantify the structural joint damage and progression herein are available. Computed tomography and magnetic resonance imaging are newer, more sensitive methods for detection and monitoring of structural joint damage. A validated scoring system for magnetic resonance imaging of the hands and wrists exists, while no consensus has been reached on a scoring system for computed tomography. Structural damage identified by either CR or magnetic resonance imaging predicts a poorer disease course in patients with both early and established rheumatoid arthritis.
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Affiliation(s)
- Lykke Midtbøll Ørnbjerg
- Copenhagen Center for Arthritis Research, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Valdemar Hansens Vej 17, 2600, Glostrup, Denmark.
| | - Mikkel Østergaard
- Copenhagen Center for Arthritis Research, COPECARE, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Valdemar Hansens Vej 17, 2600, Glostrup, Denmark.
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Sivak WN, Imbriglia JE. Evaluation of Cartilage in the Wrist using Magnetic Resonance Imaging. Curr Rheumatol Rev 2019; 16:170-177. [PMID: 31804162 DOI: 10.2174/1573397115666190819153912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 06/18/2019] [Accepted: 08/20/2019] [Indexed: 11/22/2022]
Abstract
Wrist pain is a common patient complaint with a myriad of clinical conditions that can explain the underlying cause. Short of wrist arthroscopy, no technique other than formal wrist arthrotomy exists for direct examination of the hyaline cartilage coating the articular surfaces of the carpal bones. Magnetic resonance imaging (MRI) has been proven accurate in evaluating joint surfaces of large joints such as the shoulder, hip, and knee with articular cartilage surface thickness is in excess of 1 mm. However, in the carpus the thickness of the cartilage and the contours present have precluded accurate imaging. Advances in MRI technology over the last several decades are now making imaging of small joint surfaces, such as the carpus, an area worth revisiting. Herein we provide a review of these efforts with a specific focus on the evaluation of the wrist.
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Affiliation(s)
- Wesley N Sivak
- Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, United States
| | - Joseph E Imbriglia
- Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States
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Peterfy C, Kremer J, Rigby W, Singer N, Birchwood C, Gill D, Reiss W, Pei J, Michalska M. Magnetic Resonance Imaging (MRI) Results Following Discontinuation of Methotrexate in Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab: The COMP-ACT MRI Substudy. J Rheumatol 2019; 47:325-332. [PMID: 31154414 DOI: 10.3899/jrheum.180953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX. METHODS In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to discontinue MTX (TCZ monotherapy; mono) or continue TCZ + MTX until Week 52. In a subset of patients, 1.5-Tesla MRI was used to obtain images of bilateral hands and wrists at weeks 24 and 40. Outcomes included changes in MRI-assessed synovitis, osteitis, erosion, and cartilage loss from Week 24 to Week 40, and in the proportion of patients with progression of each score. RESULTS Of 296 patients who achieved DAS28-ESR ≤ 3.2 at Week 24, 79 were enrolled in the pilot MRI substudy and randomized to TCZ mono (n = 38) or TCZ + MTX (n = 41). Treatment with either TCZ mono or TCZ + MTX suppressed erosion progression, synovitis, osteitis, and cartilage loss. The proportion of patients with no progression in each outcome measure was similar between groups (range, TCZ mono: 84.8-97.0%; TCZ + MTX: 92.3-100%). CONCLUSION In a subset of patients who achieved low disease activity with TCZ + MTX, MRI changes were minimal in intraarticular inflammation and damage measures in patients who discontinued MTX versus those who continued TCZ + MTX.
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Affiliation(s)
- Charles Peterfy
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA. .,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc.
| | - Joel Kremer
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - William Rigby
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - Nora Singer
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - Christine Birchwood
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - Darcy Gill
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - William Reiss
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - Jinglan Pei
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
| | - Margaret Michalska
- From Spire Sciences Inc., Boca Raton, Florida; Albany Medical College and The Center for Rheumatology, Albany, New York; Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire; Case Western Reserve University and MetroHealth System, Cleveland, Ohio; Genentech Inc., South San Francisco, California, USA.,C. Peterfy, MD, Spire Sciences Inc.; J. Kremer, MD, Albany Medical College and The Center for Rheumatology; W. Rigby, MD, Geisel School of Medicine, Dartmouth College; N. Singer, MD, Case Western Reserve University and MetroHealth System; C. Birchwood, PhD, Genentech Inc.; D. Gill, BS, Genentech Inc.; W. Reiss, PharmD, Genentech Inc.; J. Pei, BS, Genentech Inc.; M. Michalska, MD, Genentech Inc
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Peterfy C, DiCarlo J, Emery P, Genovese MC, Keystone EC, Taylor PC, Schlichting DE, Beattie SD, Luchi M, Macias W. MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis. J Rheumatol 2019; 46:887-895. [PMID: 30647190 DOI: 10.3899/jrheum.171469] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Magnetic resonance imaging (MRI) was used in a phase IIb study of baricitinib in patients with RA to support dose selection for the phase III program. METHODS Three hundred one patients with active RA who were taking stable methotrexate were randomized 2:1:1:1:1 to placebo or once-daily baricitinib (1, 2, 4, or 8 mg) for up to 24 weeks. One hundred fifty-four patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and at weeks 12 and 24. Two expert radiologists, blinded to treatment and visit order, scored images for synovitis, osteitis, bone erosion, and cartilage loss. Combined inflammation (osteitis + 3× synovitis score) and total joint damage (erosion + 2.5× cartilage loss score) scores were calculated. Treatment groups were compared using ANCOVA adjusting for baseline scores. RESULTS Mean changes from baseline to Week 12 for synovitis were -0.10, -1.50, and -1.60 for patients treated with placebo, baricitinib 4 mg, and baricitinib 8 mg, respectively (p = 0.003 vs placebo for baricitinib 4 and 8 mg). Mean changes for osteitis were 0.00, -3.20, and -2.10 (p = 0.001 vs placebo for baricitinib 4 mg and p = 0.037 for 8 mg), respectively. Mean changes for bone erosion were 0.90, 0.10, and 0.40 (p = 0.089 for 4 mg and p = 0.275 for 8 mg), respectively, in these treatment groups. CONCLUSION MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4 and 8 mg. This corroborates previously demonstrated clinical efficacy of baricitinib and increases confidence that baricitinib 4 mg could reduce the radiographic progression in phase III studies. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01185353].
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Affiliation(s)
- Charles Peterfy
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada. .,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co.
| | - Julie DiCarlo
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Paul Emery
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Mark C Genovese
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Edward C Keystone
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Peter C Taylor
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Doug E Schlichting
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Scott D Beattie
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - Monica Luchi
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
| | - William Macias
- From Spire Sciences Inc., Boca Raton, Florida; Division of Immunology and Rheumatology, Stanford University, Stanford, California; Eli Lilly and Co., Indianapolis, Indiana; Incyte Corporation, Wilmington, Delaware, USA; The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; Botnar Research Centre, University of Oxford, Oxford, UK; Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada.,C. Peterfy, MD, PhD, Spire Sciences Inc.; J. DiCarlo, PhD, Spire Sciences Inc.; P. Emery, MD, FRCP, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds; M.C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University; E.C. Keystone, MD, FRCP, Department of Rheumatology, University of Toronto; P.C. Taylor, MA, PhD, FRCP, Botnar Research Centre, University of Oxford; D.E. Schlichting, RN, PhD, Eli Lilly and Co.; S.D. Beattie, PhD, Eli Lilly and Co.; M. Luchi, MD, FACR, MBA, Incyte Corp.; W. Macias, MD, PhD, Eli Lilly and Co
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11
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Pradsgaard DØ, Hørlyck A, Spannow AH, Heuck C, Herlin T. A Comparison of Radiographic Joint Space Width Measurements Versus Ultrasonographic Assessment of Cartilage Thickness in Children with Juvenile Idiopathic Arthritis. J Rheumatol 2018; 46:301-308. [PMID: 30442828 DOI: 10.3899/jrheum.170571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2018] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Joint space narrowing (JSN) is a measurable outcome of tissue degeneration in arthritis. JSN is usually assessed by conventional radiography. Ultrasonographic (US) measurement of joint cartilage thickness has been validated in healthy children, and US measurement of the distal femoral cartilage has been validated in a group of patients with juvenile idiopathic arthritis (JIA). Our aim was to compare the measures of cartilage thickness of the proximal cartilage site in the second metacarpophalangeal (MCP), second proximal interphalangeal (PIP), and knee joints as assessed by US to joint space width (JSW) as measured by computerized radiography in children with JIA. METHODS The study included 74 children with JIA aged 5-15 years (median 11.3 yrs). MCP and PIP joints were assessed at one midline spot. Knee joints were assessed at the medial and lateral femoral condylar areas. Only the proximal cartilage site in the joints was assessed by US, whereas the complete JSW was assessed by radiography. RESULTS We assessed 136 second MCP, 138 second PIP, and 146 knee joints. We found a high level of agreement between US and radiographic measures of cartilage thickness and JSW: r = 0.82-0.86 (second MCP), r = 0.50-0.55 (second PIP), and r = 0.52-0.81 (knee); p < 0.001 for all 8 assessed sites. CONCLUSION US measurements of cartilage thickness of the proximal site of the second MCP, second PIP, and knee joints correlated well with radiographic JSW measurements in the finger and knee joints of children with JIA. However, US does not measure the distal cartilage, which may limit its use in the assessment of JSN.
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Affiliation(s)
- Dan Østergaard Pradsgaard
- From the Department of Pediatrics, and the Department of Radiology, Aarhus University Hospital, Aarhus, Denmark. .,D.Ø. Pradsgaard, MD, PhD, Department of Pediatrics, Aarhus University Hospital; A. Hørlyck, MD, Department of Radiology, Aarhus University Hospital; A.H. Spannow, MD, PhD, Department of Pediatrics, Aarhus University Hospital; C. Heuck, MD, PhD, Department of Pediatrics, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital.
| | - Arne Hørlyck
- From the Department of Pediatrics, and the Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.,D.Ø. Pradsgaard, MD, PhD, Department of Pediatrics, Aarhus University Hospital; A. Hørlyck, MD, Department of Radiology, Aarhus University Hospital; A.H. Spannow, MD, PhD, Department of Pediatrics, Aarhus University Hospital; C. Heuck, MD, PhD, Department of Pediatrics, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital
| | - Anne Helene Spannow
- From the Department of Pediatrics, and the Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.,D.Ø. Pradsgaard, MD, PhD, Department of Pediatrics, Aarhus University Hospital; A. Hørlyck, MD, Department of Radiology, Aarhus University Hospital; A.H. Spannow, MD, PhD, Department of Pediatrics, Aarhus University Hospital; C. Heuck, MD, PhD, Department of Pediatrics, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital
| | - Carsten Heuck
- From the Department of Pediatrics, and the Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.,D.Ø. Pradsgaard, MD, PhD, Department of Pediatrics, Aarhus University Hospital; A. Hørlyck, MD, Department of Radiology, Aarhus University Hospital; A.H. Spannow, MD, PhD, Department of Pediatrics, Aarhus University Hospital; C. Heuck, MD, PhD, Department of Pediatrics, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital
| | - Troels Herlin
- From the Department of Pediatrics, and the Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.,D.Ø. Pradsgaard, MD, PhD, Department of Pediatrics, Aarhus University Hospital; A. Hørlyck, MD, Department of Radiology, Aarhus University Hospital; A.H. Spannow, MD, PhD, Department of Pediatrics, Aarhus University Hospital; C. Heuck, MD, PhD, Department of Pediatrics, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital
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12
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AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis. Int J Rheumatol 2018; 2018:8721753. [PMID: 29849651 PMCID: PMC5925169 DOI: 10.1155/2018/8721753] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 02/13/2018] [Accepted: 02/26/2018] [Indexed: 11/21/2022] Open
Abstract
Aim Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). Methods In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). Results 52 subjects were enrolled (80% female, mean (SD) age 57 (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. Conclusion Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. Trial registration This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703).
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13
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Beals C, Baumgartner R, Peterfy C, Balanescu A, Mirea G, Harabagiu A, Popa S, Cheng A, Feng D, Ashton E, DiCarlo J, Vallee MH, Dardzinski BJ. Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring. PLoS One 2017; 12:e0187397. [PMID: 29236711 PMCID: PMC5728526 DOI: 10.1371/journal.pone.0187397] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 09/24/2017] [Indexed: 02/06/2023] Open
Abstract
The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63–1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55–1.45)), RAMRIS synovitis (0.85 (0.38–1.28)) and RAMRIS osteitis (0.99 (0.52–1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. (ClinicalTrials.gov registration: NCT01313520)
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Affiliation(s)
- Chan Beals
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
- * E-mail:
| | - Richard Baumgartner
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
| | - Charles Peterfy
- Spire Sciences, Inc., Boca Raton, Florida, United States of America
| | - Andra Balanescu
- Department of Immunology, U of Med and Pharm Carol Davila, Bucharest, Romania
| | - Gavrila Mirea
- Department of Rheumatology, Tractorul County Hospital, Brasov, Romania
| | | | - Serghei Popa
- Department of Rheumatology, Republican Clinical Hospital, Chisinau, MD, Moldova
| | - Amy Cheng
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
| | - Dai Feng
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
| | - Edward Ashton
- VirtualScopics, Rochester, New York, United States of America
| | - Julie DiCarlo
- Spire Sciences, Inc., Boca Raton, Florida, United States of America
| | - Marie-Helene Vallee
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
| | - Bernard J. Dardzinski
- Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America
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14
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Barile A, Arrigoni F, Bruno F, Guglielmi G, Zappia M, Reginelli A, Ruscitti P, Cipriani P, Giacomelli R, Brunese L, Masciocchi C. Computed Tomography and MR Imaging in Rheumatoid Arthritis. Radiol Clin North Am 2017; 55:997-1007. [DOI: 10.1016/j.rcl.2017.04.006] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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15
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Woodworth TG, Morgacheva O, Pimienta OL, Troum OM, Ranganath VK, Furst DE. Examining the validity of the rheumatoid arthritis magnetic resonance imaging score according to the OMERACT filter-a systematic literature review. Rheumatology (Oxford) 2017; 56:1177-1188. [PMID: 28398508 PMCID: PMC5850856 DOI: 10.1093/rheumatology/kew445] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 11/01/2016] [Indexed: 02/05/2023] Open
Abstract
Objective To examine whether the RA MRI score (RAMRIS) for RA of the wrist/hand meets the OMERACT filter criteria-truth (validity), discrimination and feasibility. Methods We conducted a systematic literature review in PubMed and Scopus, from 1970 through June 2014, focused on MRI measures of synovitis, osteitis/bone marrow oedema, erosions and/or joint space narrowing in RA randomized controlled trials and observational studies with cohort size ⩾10. Strength of evidence was assessed using the Cochrane Handbook criteria. Results Of 634 MRI titles/abstracts, 202 met the review criteria, with 92 providing at least 1 type of validity. Four articles provided criterion validity, and 26 articles utilized RAMRIS to assess 1.5 T MRI images. Histopathology data showed inflammation corresponding to MRI of synovitis and osteitis. MRI erosions corresponded to those identified with CT. Content and construct validity for RAMRIS synovitis, osteitis and erosions were documented by correlations with clinical, laboratory and/or radiographic data. Each measure was sensitive to change and responsive to therapy. RAMRIS synovitis and osteitis were able to discriminate between the efficacy of treatments vs placebo in 12-week studies, whereas RAMRIS erosions required studies of ⩾24 weeks. Conclusion RAMRIS synovitis, osteitis and erosions imaged with 1.5 T MRI are valid and useful for evaluating joint inflammation and damage for RA of the wrist/hand, according to the OMERACT filter.
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Affiliation(s)
- Thasia G. Woodworth
- Department of Medicine, Division of Rheumatology, David Geffen School of
Medicine, UCLA, Los Angeles
| | - Olga Morgacheva
- Department of Medicine, Division of Rheumatology, David Geffen School of
Medicine, UCLA, Los Angeles
| | - Olga L. Pimienta
- Keck School of Medicine, University of Southern California, Santa Monica,
CA, USA
| | - Orrin M. Troum
- Keck School of Medicine, University of Southern California, Santa Monica,
CA, USA
| | - Veena K. Ranganath
- Department of Medicine, Division of Rheumatology, David Geffen School of
Medicine, UCLA, Los Angeles
| | - Daniel E. Furst
- Department of Medicine, Division of Rheumatology, David Geffen School of
Medicine, UCLA, Los Angeles
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16
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Peterfy C, Strand V, Tian L, Østergaard M, Lu Y, DiCarlo J, Countryman P, Deodhar A, Landewé R, Ranganath VK, Troum O, Conaghan PG. Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials. Ann Rheum Dis 2017; 76:992-997. [PMID: 27974302 DOI: 10.1136/annrheumdis-2016-210311] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Revised: 11/06/2016] [Accepted: 11/20/2016] [Indexed: 01/27/2023]
Abstract
OBJECTIVE In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. METHODS Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. RESULTS Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). CONCLUSIONS Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.
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Affiliation(s)
| | - Vibeke Strand
- Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA
| | - Lu Tian
- Department of Biomedical Data Science, Stanford University, Palo Alto, California, USA
| | - Mikkel Østergaard
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ying Lu
- Department of Biomedical Data Science, Stanford University, Palo Alto, California, USA
| | | | | | - Atul Deodhar
- Division of Arthritis & Rheumatic Diseases (OPO9), Oregon Health & Science University, Portland, Oregon, USA
| | - Robert Landewé
- Amsterdam Rheumatology & Immunology Center (ARC)(AMC), Amsterdam, The Netherlands
- Zuyderland Medical Center, Heerlen, The Netherlands
| | - Veena K Ranganath
- Division of Rheumatology, University of California, Los Angeles, California, USA
- David Geffen School of Medicine, Los Angeles, California, USA
| | - Orrin Troum
- The Doctors of Saint John's Medical Group, Providence Saint John's Health Center, Santa Monica, California, USA
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Philip G Conaghan
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
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17
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Peterfy C, Emery P, Tak PP, Østergaard M, DiCarlo J, Otsa K, Navarro Sarabia F, Pavelka K, Bagnard MA, Gylvin LH, Bernasconi C, Gabriele A. MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study. Ann Rheum Dis 2016; 75:170-7. [PMID: 25355728 PMCID: PMC4717395 DOI: 10.1136/annrheumdis-2014-206015] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 09/24/2014] [Accepted: 10/05/2014] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. METHODS Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. RESULTS Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. CONCLUSIONS This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. TRIAL REGISTRATION NUMBER NCT00578305.
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Affiliation(s)
| | - Paul Emery
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Paul P Tak
- *Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; *Current address also: University of Cambridge, Cambridge, UK and GlaxoSmithKline, Stevenage, UK
| | - Mikkel Østergaard
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital. University of Copenhagen, Copenhagen, Denmark
| | | | - Kati Otsa
- Tallinn Central Hospital, Tallinn, Estonia
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Zink JV, Souteyrand P, Guis S, Chagnaud C, Fur YL, Militianu D, Mattei JP, Rozenbaum M, Rosner I, Guye M, Bernard M, Bendahan D. Standardized quantitative measurements of wrist cartilage in healthy humans using 3T magnetic resonance imaging. World J Orthop 2015; 6:641-648. [PMID: 26396941 PMCID: PMC4573509 DOI: 10.5312/wjo.v6.i8.641] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 06/17/2015] [Accepted: 08/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To quantify the wrist cartilage cross-sectional area in humans from a 3D magnetic resonance imaging (MRI) dataset and to assess the corresponding reproducibility.
METHODS: The study was conducted in 14 healthy volunteers (6 females and 8 males) between 30 and 58 years old and devoid of articular pain. Subjects were asked to lie down in the supine position with the right hand positioned above the pelvic region on top of a home-built rigid platform attached to the scanner bed. The wrist was wrapped with a flexible surface coil. MRI investigations were performed at 3T (Verio-Siemens) using volume interpolated breath hold examination (VIBE) and dual echo steady state (DESS) MRI sequences. Cartilage cross sectional area (CSA) was measured on a slice of interest selected from a 3D dataset of the entire carpus and metacarpal-phalangeal areas on the basis of anatomical criteria using conventional image processing radiology software. Cartilage cross-sectional areas between opposite bones in the carpal region were manually selected and quantified using a thresholding method.
RESULTS: Cartilage CSA measurements performed on a selected predefined slice were 292.4 ± 39 mm2 using the VIBE sequence and slightly lower, 270.4 ± 50.6 mm2, with the DESS sequence. The inter (14.1%) and intra (2.4%) subject variability was similar for both MRI methods. The coefficients of variation computed for the repeated measurements were also comparable for the VIBE (2.4%) and the DESS (4.8%) sequences. The carpus length averaged over the group was 37.5 ± 2.8 mm with a 7.45% between-subjects coefficient of variation. Of note, wrist cartilage CSA measured with either the VIBE or the DESS sequences was linearly related to the carpal bone length. The variability between subjects was significantly reduced to 8.4% when the CSA was normalized with respect to the carpal bone length.
CONCLUSION: The ratio between wrist cartilage CSA and carpal bone length is a highly reproducible standardized measurement which normalizes the natural diversity between individuals.
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Mathew AJ, Bird P. Utility of in-office extremity magnetic resonance imaging in rheumatology. INDIAN JOURNAL OF RHEUMATOLOGY 2015. [DOI: 10.1016/j.injr.2015.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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20
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Popovich I, Lee AC, Doyle A, McHaffie A, Clarke A, Reeves Q, Dalbeth N, McQueen FM. A comparative MRI study of cartilage damage in gout versus rheumatoid arthritis. J Med Imaging Radiat Oncol 2015; 59:431-435. [PMID: 25908527 DOI: 10.1111/1754-9485.12306] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Accepted: 02/19/2015] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Magnetic resonance imaging (MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis (RA). METHODS Forty patients with gout and 38 with seropositive RA underwent 3T-MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema (BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis. RESULTS Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group (P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56). CONCLUSIONS Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions.
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Affiliation(s)
- Ivor Popovich
- Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
| | - Arier Cl Lee
- Department of Epidemiology and Biostatistics, Tamaki Campus, University of Auckland, Auckland, New Zealand
| | - Anthony Doyle
- Department of Radiology, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Alexandra McHaffie
- Department of Radiology, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Andrew Clarke
- Department of Radiology, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Quentin Reeves
- Department of Radiology, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand
| | - Nicola Dalbeth
- Bone & Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.,Department of Rheumatology, Auckland District Health Board, Greenlane Clinical Centre, Auckland, New Zealand
| | - Fiona M McQueen
- Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.,Department of Rheumatology, Auckland District Health Board, Greenlane Clinical Centre, Auckland, New Zealand
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21
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Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist. Skeletal Radiol 2015; 44:539-47. [PMID: 25488101 DOI: 10.1007/s00256-014-2059-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 10/08/2014] [Accepted: 11/06/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.
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Glinatsi D, Lillegraven S, Haavardsholm EA, Eshed I, Conaghan PG, Peterfy C, Gandjbakhch F, Bird P, Bøyesen P, Døhn UM, Genant HK, Østergaard M. Validation of the OMERACT Magnetic Resonance Imaging Joint Space Narrowing Score for the Wrist in a Multireader Longitudinal Trial. J Rheumatol 2015; 42:2480-5. [DOI: 10.3899/jrheum.141009] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Objective.To assess the intrareader and interreader agreement and sensitivity to change of the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Joint Space Narrowing (RAMRIS-JSN) score in the rheumatoid arthritis (RA) wrist in a longitudinal multireader exercise.MethodsCoronal T1-weighted MR image sets of 1 wrist from 20 patients with early RA were assessed twice for JSN at 17 sites at baseline and after 36 or 60 months by 4 readers blinded to patient data but not time order. The joints were scored 0–4 according to the OMERACT RAMRIS-JSN score. Intraclass correlation coefficients (ICC), smallest detectable change (SDC), percentage exact/close agreement (PEA/PCA), and standardized response mean (SRM) were calculated.Results.Median baseline and change score was 10.3 and 1.9, respectively. Intrareader ICC for baseline and change scores was good (≥ 0.50) to very good (≥ 0.80) for all and 3 of 4 readers, respectively. Interreader ICC was very good for change (0.93), while poor for baseline score if all 4 readers were included (0.36), but very good if 1 reader was excluded (0.87). Intrareader and interreader SDC was low (2.34–3.18), except for the intrareader SDC for 1 reader (6.75). The mean PEA/PCA was high for baseline and change scores both within and between the readers (51.5–99.2), except for interreader baseline PEA (14.4). SRM was moderate for all readers (0.55–0.77).Conclusion.The OMERACT RAMRIS-JSN score showed high overall intrareader and interreader reliability, and moderate sensitivity to change, supporting inclusion of the measure as part of the OMERACT RAMRIS system.
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23
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Abstract
Magnetic resonance imaging (MRI) is ideal for imaging the joints of rheumatoid arthritis (RA) patients. It produces anatomically detailed images of bone, cartilage, tendons and synovial membrane. It can reveal structural damage, in the form of bone erosion, cartilage thinning and/or tendon rupture, and regions of inflammation, using sequences that reveal water content and vascularity. MRI synovitis, tenosynovitis and bone oedema/osteitis all have prognostic significance, and MRI studies of RA have helped elucidate the mechanisms whereby bone and synovial inflammation lead to joint damage. Bone oedema/osteitis has become an important imaging biomarker, and can be used to help predict progression from undifferentiated arthritis to definite RA. Recent MRI studies have confirmed that subclinical inflammation is often present in patients in clinical remission, and these data may affect disease management. Finally, recent clinical trials are reviewed, in which MRI outcome measures are being established as sensitive response markers.
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Affiliation(s)
- Fiona M McQueen
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand,
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24
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Herz B, Albrecht A, Englbrecht M, Welsch GH, Uder M, Renner N, Schlechtweg P, Paul D, Lauer L, Engelke K, Janka R, Rech J, Schett G, Finzel S. Osteitis and synovitis, but not bone erosion, is associated with proteoglycan loss and microstructure damage in the cartilage of patients with rheumatoid arthritis. Ann Rheum Dis 2014; 73:1101-6. [PMID: 23625980 DOI: 10.1136/annrheumdis-2012-202850] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To investigate the relation between anatomic changes of the synovium, the bone, the bone marrow and the cartilage to biochemical properties of the cartilage in patients with rheumatoid arthritis (RA). METHODS 33 patients with RA received 3-T MRI scans of the metacarpophalangeal joints. Two independent methods, (A) the delayed gadolinium enhanced MRI of the cartilage (dGEMRIC, T2-mapping), which was used to assess the biochemical properties of the cartilage; (B) synovitis, osteitis and bone erosions were quantified according to the RA MRI scoring (RAMRIS) method and cartilage thickness (CT), interbone joint space (IBJS, distance between proximal and distal bone surface) and intercartilage joint space (ICJS, distance between proximal and distal cartilage surface) were measured. RESULTS Biochemical changes of the cartilage, corresponding to low dGEMRIC and high T2 values, were more likely to be seen in joints with decreased IBJS and ICJS as well as decreased CT. For instance, dGEMRIC was directly correlated to the IBJS (p=0.001) and ICJS (p=0.001), whereas T2 mapping was inversely correlated to IBJS and ICJS (both p=0.017). Moreover, the degree of osteitis, and to some extent synovitis, was correlated to biochemical cartilage changes as measured by dGEMRIC (p=0.003) or the T2 mapping (p=0.013). By contrast, bone erosions did not correlate to the degree of biochemical cartilage changes. DISCUSSION These data support the concept that synovitis and osteitis may be two main triggers for cartilage damage. Thus, the actual inflammatory state of a joint, but not so much the degree of bone erosion, appears to influence cartilage properties in RA.
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Affiliation(s)
- Barbara Herz
- Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, , Erlangen, Germany
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Abstract
Over the last two decades, MRI has emerged as an important clinical tool to assist in the diagnosis and management of rheumatic disease. In rheumatoid arthritis (RA), MRI has improved our understanding of the pathological basis of disease and has provided new information about imaging features that reflect joint inflammation and damage. Using MRI, we can now directly observe inflammation involving the synovial membrane and tenosynovium, plus joint damage including bone erosion and cartilage thinning. Inflammation of bone beneath the joint (osteitis) appears as bone oedema which is a feature unique to MRI and yields important diagnostic and prognostic information in patients with inflammatory arthritis. With the introduction of biologics to rheumatology clinical practice, sensitive tools are required to monitor disease activity and progression, so that the disease suppressing effect of these new agents can be measured. MRI fits the bill for this role as it can inform the clinician about the development of bone erosions well before plain radiography, and its ability to reveal cartilage damage is emerging. The use of MRI as a marker of outcome in clinical trials is being paralleled by its increasing role in the clinic. Both extremity and high field MRI have clinical applications in RA and need to be considered along with other advanced imaging techniques as useful tools to add to the clinician's armamentarium. This review will summarise recent advances in this field and will apply current knowledge to specific clinical scenarios relevant to modern rheumatology practice.
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26
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Vermeij EA, Koenders MI, Blom AB, Arntz OJ, Bennink MB, van den Berg WB, van Lent PL, van de Loo FA. In Vivo Molecular Imaging of Cathepsin and Matrix Metalloproteinase Activity Discriminates between Arthritic and Osteoarthritic Processes in Mice. Mol Imaging 2014. [DOI: 10.2310/7290.2014.00001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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27
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Døhn UM, Conaghan PG, Eshed I, Boonen A, Boyesen P, Peterfy CG, Lillegraven S, Ejbjerg B, Gandjbakhch F, Bird P, Foltz V, Genant HK, Haavardsholm E, McQueen FM, Østergaard M. The OMERACT-RAMRIS Rheumatoid Arthritis Magnetic Resonance Imaging Joint Space Narrowing Score: Intrareader and Interreader Reliability and Agreement with Computed Tomography and Conventional Radiography. J Rheumatol 2013; 41:392-7. [DOI: 10.3899/jrheum.131087] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Objective.To test the intrareader and interreader reliability of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints on magnetic resonance imaging (MRI) and computed tomography (CT) using the newly proposed OMERACT-RAMRIS JSN scoring method, and to compare JSN assessment on MRI, CT, and radiography.Methods.After calibration of readers, MRI and CT images of the wrist and second to fifth MCP joints from 14 patients with RA and 1 healthy control were assessed twice for JSN by 3 readers, blinded to clinical and imaging data. Radiographs were scored by the Sharp/van der Heijde method. Intraclass correlation coefficients (ICC) and smallest detectable differences (SDD) were calculated, and the performance of various simplified scores was investigated.Results.Both MRI and CT showed high intrareader (ICC ≥ 0.95) and interreader (ICC ≥ 0.94) reliability for total (wrist + MCP) assessment of JSN. Agreement was generally lower for MCP joints than for wrist joints, particularly for CT. Intrareader SDD for MCP/wrist/MCP + wrist were 1.2/6.1/6.4 JSN units for MRI, while 2.7/8.3/9.9 JSN units for CT. JSN on MRI and CT correlated moderately well with corresponding radiographic JSN scores (MCP 2–5: 0.49 and 0.56; wrist areas assessed by Sharp/van der Heijde: 0.80 and 0.95), and high ICC between scores on MRI and CT were demonstrated (MCP: 0.94; wrist: 0.92; MCP + wrist: 0.92).Conclusion.The OMERACT-RAMRIS MRI JSN scoring system showed high intrareader and interreader reliability, and high correlation with CT scores of JSN. The suggested JSN score may, after further validation in longitudinal studies, become a useful tool in RA clinical trials.
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Damasio MB, Horatio LTD, Boavida P, Lambot-Juhan K, Rosendahl K, Tomà P, Muller LSO. Imaging in juvenile idiopathic arthritis (JIA): an update with particular emphasis on MRI. Acta Radiol 2013; 54:1015-23. [PMID: 23873885 DOI: 10.1177/0284185113493777] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Juvenile idiopathic arthritis (JIA) is a heterogeneous condition encompassing all forms of chronic arthritis of unknown origin and with onset before 16 years of age. During the last decade new, potent therapeutic agents have become available, underscoring the need for accurate monitoring of therapeutic response on both disease activity and structural damage to the joint. However, so far, treatment efficacy is based on clinical ground only, although clinical parameters are poor markers for disease activity and progression of structural damage. Not so for rheumatoid arthritis patients where the inclusion of radiographic assessment has been required by FDA to test the disease-modifying potential of new anti-rheumatic drugs. In imaging of children with JIA there has been a shift from traditional radiography towards newer techniques such as ultrasound and MRI, however without proper evaluation of their accuracy and validity. We here summarize present knowledge and discuss future challenges in imaging children with JIA.
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Affiliation(s)
| | - L Tantum de Horatio
- Department of Radiology, Bambino Gesu Children's Hospital, IRCCS, Rome, Italy
| | - P Boavida
- Department of Radiology, Great Ormond Street Hospital for Children, London, UK
| | - K Lambot-Juhan
- Department of Radiology, Hopital Necker Enfants Malades, Paris, France
| | - K Rosendahl
- Department of Radiology, Haukeland University Hospital, Bergen, Norway
- Department of Surgical Sciences, University of Bergen, Bergen, Norway
| | - P Tomà
- Department of Radiology, Bambino Gesu Children's Hospital, IRCCS, Rome, Italy
| | - LS Ording Muller
- Department of Radiology, University Hospital North Norway, Troms⊘, Norway
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Abstract
The success of modern rheumatoid arthritis (RA) therapies and treatment strategies has led to extended placebo phases being unethical in RA randomised controlled trials (RCTs). Modern trials therefore increasingly involve active comparator designs, and this together with some technical issues has meant difficulties in differentiating structural progression using traditional radiographic outcome measures. Magnetic resonance imaging (MRI) has been demonstrated to assess damage more sensitively than radiographs, but importantly it can measure the upstream drivers of erosions and cartilage loss, synovitis and osteitis. An increasing number of recent RCTs using the RA MRI scoring system (RAMRIS) have demonstrated the ability of MRI to discriminate progression and treatment effect. Consistency of erosion progression determination was seen across the majority of these studies. In most studies, MRI demonstrated reduction in synovitis and osteitis at early (12 week) timepoints, and MRI predicted subsequent radiographic findings. Often small numbers of patients were required to demonstrate such changes. The time is right for regulatory authorities to include MRI as an alternative to radiographic data in support of claims of inhibition of progression of structural damage in RA trials.
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30
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Peterfy CG, Olech E, DiCarlo JC, Merrill JT, Countryman PJ, Gaylis NB. Monitoring cartilage loss in the hands and wrists in rheumatoid arthritis with magnetic resonance imaging in a multi-center clinical trial: IMPRESS (NCT00425932). Arthritis Res Ther 2013; 15:R44. [PMID: 23514433 PMCID: PMC4060230 DOI: 10.1186/ar4202] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Revised: 01/28/2013] [Accepted: 03/20/2013] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Magnetic resonance imaging (MRI) is increasingly being used in clinical trials of rheumatoid arthritis (RA) because of its superiority over x-ray radiography (XR) in detecting and monitoring change in bone erosion, osteitis and synovitis. However, in contrast to XR, the MRI scoring method that was used in most clinical trials did not include cartilage loss. This limitation has been an obstacle to accepting MRI as a potential alternative to XR in clinical trials. Cross-sectional studies have shown MRI to be sensitive for cartilage loss in the hands and wrist; although, longitudinal sensitivity to change has not yet been confirmed. In this study we examined the ability of MRI to monitor change in cartilage loss in patients with RA in a multi-site clinical trial setting. METHODS Thirty-one active RA patients from a clinical trial (IMPRESS) who were randomized equally into treatment with either rituximab + methotrexate or placebo + methotrexate had MRI of the dominant hand/wrist at baseline, 12 weeks and 24 weeks at 3 clinical sites in the US. Twenty-seven of these patients also had XR of both hands/wrists and both feet at baseline and 24 weeks. One radiologist scored all XR images using the van der Heijde-modified Sharp method blinded to visit order. The same radiologist scored MR images for cartilage loss using a previously validated 9-point scale, and bone erosion using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI Score (RAMRIS) blinded to visit order and XR scores. Data from the two treatment arms were pooled for this analysis. RESULTS Mean MRI cartilage score increased at 12 and 24 weeks, and reached statistical significance at 24 weeks. XR total Sharp score, XR erosion score and XR joint-space narrowing (JSN) score all increased at 24 weeks, but only XR total Sharp score increased significantly. CONCLUSIONS To our knowledge, this is the first publication of a study demonstrating MRI's ability to monitor cartilage loss in a multi-site clinical trial. Combined with MRI's established performance in monitoring bone erosions in RA, these findings suggest that MRI may offer a superior alternative to XR in multi-site clinical trials of RA.
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Affiliation(s)
| | - Ewa Olech
- Division of Rheumatology, School of Medicine, University of Nevada, 1707 W. Charleston Blvd, Las Vegas, Nevada, 89102, USA
| | - Julie C DiCarlo
- Spire Sciences, Inc., 5314 Boca Marina Cir N, Boca Raton, FL, USA
| | - Joan T Merrill
- Oklahoma Medical Research Foundation, 825 NE 13th St, Oklahoma City, Oklahoma, 73104, USA
| | | | - Norman B Gaylis
- Arthritis & Rheumatic Disease Specialties, 21097 NE 27th Court, Suite 200, Aventura, Florida, 33180, USA
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Conaghan PG, Ostergaard M, D'Agostino MA, Gaylis N, Arnold W, Olech E, Wells A, Peterfy C, Seraphine JL, Troum O. Proceedings from the 5th Annual International Society for Musculoskeletal Imaging in Rheumatology Annual Conference. Semin Arthritis Rheum 2013; 42:433-46. [PMID: 23415135 DOI: 10.1016/j.semarthrit.2012.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 10/15/2012] [Indexed: 10/27/2022]
Abstract
Since its inception, ISEMIR has held an annual education meeting highlighting the changes in the utilization of imaging tools for the management of rheumatic diseases. ISEMIR's international faculty and world-renowned experts have discussed these topics at a very high scientific level. The evolution of the content demonstrates the rapidly changing environment in the field of rheumatology. Advances in treatment have led to the increased use of magnetic resonance imaging (MRI) and ultrasound (US). This publication is based upon the proceedings from the 2012 ISEMIR educational meeting that took place on April 26th in Chicago, Illinois. Presentations from the live proceedings can be viewed at www.isemir.org.
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