A Double-blind, Randomized Controlled Trial to Compare the Effect of Biannual Peripheral Magnetic Resonance Imaging, Radiography and Standard of Care Disease Progression Monitoring on Pharmacotherapeutic Escalation in Rheumatoid and Undifferentiated...

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2014 Jul 7

PMID 24997587

Citations 1

Authors

Ruben Tavares

Karen Anne Beattie

William George Bensen

Raja S Bobba

Alfred A Cividino

Karen Finlay

Ron Goeree

Lawrence Errol Hart

Erik Jurriaans

Maggie J Larche

Naveen Parasu

Jean-Eric Tarride

Colin E Webber

Jonathan D Adachi

Affiliations

Soon will be listed here.

Abstract

Background: Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA.

Methods: A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance.

Discussion: This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression.

Trial Registration: This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).

Citing Articles

Ultrasonography supplements clinical exam to improve early rheumatoid arthritis disease activity monitoring in metatarsophalangeal joints.

Zou H, Beattie K, Allen M, Ioannidis G, Larche M Clin Rheumatol. 2020; 39(5):1483-1491.

PMID: 31907694 DOI: 10.1007/s10067-019-04896-5.

References

Mason J, Anderson J, Meenan R, Haralson K, Kaine J . The rapid assessment of disease activity in rheumatology (radar) questionnaire. Validity and sensitivity to change of a patient self-report measure of joint count and clinical status. Arthritis Rheum. 1992; 35(2):156-62. DOI: 10.1002/art.1780350206. View

Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S . Continuation of methotrexate resulted in better clinical and radiographic outcomes than discontinuation upon starting etanercept in patients with rheumatoid arthritis: 52-week results from the JESMR study. J Rheumatol. 2011; 38(8):1585-92. DOI: 10.3899/jrheum.110014. View

Sharp J, Lidsky M, Collins L, Moreland J . Methods of scoring the progression of radiologic changes in rheumatoid arthritis. Correlation of radiologic, clinical and laboratory abnormalities. Arthritis Rheum. 1971; 14(6):706-20. DOI: 10.1002/art.1780140605. View

van Aken J, van Dongen H, le Cessie S, Allaart C, Breedveld F, Huizinga T . Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study. Ann Rheum Dis. 2005; 65(1):20-5. PMC: 1797989. DOI: 10.1136/ard.2005.038471. View

Bruynesteyn K, Boers M, Kostense P, van der Linden S, van der Heijde D . Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change. Ann Rheum Dis. 2004; 64(2):179-82. PMC: 1755378. DOI: 10.1136/ard.2003.018457. View

van der Heijde D, van Leeuwen M, van Riel P, van de Putte L . Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification). J Rheumatol. 1995; 22(9):1792-6. View

Egsmose C, Lund B, Borg G, Pettersson H, Berg E, Brodin U . Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol. 1995; 22(12):2208-13. View

Therneau T . How many stratification factors are "too many" to use in a randomization plan?. Control Clin Trials. 1993; 14(2):98-108. DOI: 10.1016/0197-2456(93)90013-4. View

Larsen A, Dale K, Eek M . Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn (Stockh). 1977; 18(4):481-91. DOI: 10.1177/028418517701800415. View

10.

Taves D . Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther. 1974; 15(5):443-53. DOI: 10.1002/cpt1974155443. View

11.

Brown A, Conaghan P, Karim Z, Quinn M, Ikeda K, Peterfy C . An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum. 2008; 58(10):2958-67. DOI: 10.1002/art.23945. View

12.

Haavardsholm E, Ostergaard M, Ejbjerg B, Kvan N, Uhlig T, Lilleas F . Reliability and sensitivity to change of the OMERACT rheumatoid arthritis magnetic resonance imaging score in a multireader, longitudinal setting. Arthritis Rheum. 2005; 52(12):3860-7. DOI: 10.1002/art.21493. View

13.

McQueen F, Benton N, Crabbe J, Robinson E, Yeoman S, McLean L . What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease. Ann Rheum Dis. 2001; 60(9):859-68. PMC: 1753833. View

14.

Scott D, Smith C, Kingsley G . Joint damage and disability in rheumatoid arthritis: an updated systematic review. Clin Exp Rheumatol. 2004; 21(5 Suppl 31):S20-7. View

15.

Scheel A, Hermann K, Ohrndorf S, Werner C, Schirmer C, Detert J . Prospective 7 year follow up imaging study comparing radiography, ultrasonography, and magnetic resonance imaging in rheumatoid arthritis finger joints. Ann Rheum Dis. 2005; 65(5):595-600. PMC: 1798149. DOI: 10.1136/ard.2005.041814. View

16.

Segami N, Nishimura M, Kaneyama K, Miyamaru M, Sato J, Murakami K . Does joint effusion on T2 magnetic resonance images reflect synovitis? Comparison of arthroscopic findings in internal derangements of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001; 92(3):341-5. DOI: 10.1067/moe.2001.117808. View

17.

Conaghan P, OConnor P, McGonagle D, Astin P, Wakefield R, Gibbon W . Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum. 2003; 48(1):64-71. DOI: 10.1002/art.10747. View

18.

Emery P, Genovese M, van Vollenhoven R, Sharp J, Patra K, Sasso E . Less radiographic progression with adalimumab plus methotrexate versus methotrexate monotherapy across the spectrum of clinical response in early rheumatoid arthritis. J Rheumatol. 2009; 36(7):1429-41. DOI: 10.3899/jrheum.081018. View

19.

Machold K, Stamm T, Eberl G, Nell V, Dunky A, Uffmann M . Very recent onset arthritis--clinical, laboratory, and radiological findings during the first year of disease. J Rheumatol. 2002; 29(11):2278-87. View

20.

Emery P, Breedveld F, van der Heijde D, Ferraccioli G, Dougados M, Robertson D . Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study. Arthritis Rheum. 2010; 62(3):674-82. DOI: 10.1002/art.27268. View