Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial

Abstract

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.

Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.

Design, setting, and participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.

Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.

Main outcomes and measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.

Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.

Conclusions and relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.

Trial registration: ClinicalTrials.gov Identifier: NCT01656278.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Møller-Bisgaard reported receiving grants and nonfinancial support from AbbVie during the conduct of the study and personal fees from Bristol-Myers Squibb outside the submitted work. Dr Hørslev-Petersen reported receiving grants from AbbVie during the conduct of the study and other funding from Roche and Pfizer for EULAR congress participation outside the submitted work. Dr Hetland reported receiving grants from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, and Crescendo; personal fees from Pfizer, CellTrion, Roche, Eli Lilly, Orion, Merck, and Samsung; and grants and personal fees from Biogen outside the submitted work. Dr Hetland is the chair of the DANBIO registry, which is located at her institution, which therefore receives funding annually from all providers of biological drugs in Denmark that have an agreement (postmarketing data). Dr Boesen reported receiving grants, personal fees, and other funding from Image Analysis Group; personal fees from Eli Lilly, UCB, and Abbvie; and grants from Esaote outside the submitted work. Dr Madsen reported receiving personal fees and nonfinancial support from Sobi, Abbvie, Merck Sharp & Dohme, Pfizer, Eli Lilly, Celgene, and Novartis; personal fees from UCB, Sanofi Aventis, Roche, Amgen, and Bristol-Myers Squibb outside the submitted work. Dr Bennett reported receiving personal fees from Eli Lilly, Merck Sharp & Dohme, and Novartis and nonfinancial support from Pfizer and Bristol-Myers Squibb outside the submitted work. Dr Hendricks reported receiving personal fees from AbbVie and Novartis and nonfinancial support from Pfizer and Roche outside the submitted work. Dr Bliddal reported receiving grants from Abbvie during the conduct of the study and, along with the Parker Institute, receiving support from the Oak Foundation. Dr Østergaard reported receiving grants from AbbVie during the conduct of the study and grants, personal fees, and nonfinancial support from AbbVie, Bristol-Myers Squibb, Merck, UCB, and Novartis; personal fees from Boehringer Ingelheim, Eli Lilly, Sanofi, and Regeneron; personal fees and nonfinancial support from Janssen, Pfizer, and Roche; grants and personal fees from Celgene; and personal fees from Orion and Hospira outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Patient Flow Throughout the IMAGINE-RA Randomized Clinical Trial

Figure 2.. Box and Whiskers Plots of the Co-primary Outcomes Stratified by Randomization Group

Box and whiskers plots display the sample population stratified by group. Circles denote individual patients. Boxes mark quartiles, the band inside the box is the second quartile (the median), while the upper whisker represents the upper adjacent value, the third quartile plus 1.5 times the interquartile range, and the lower whisker represents the lower adjacent value, the lower quartile minus 1.5 times the interquartile range. The dashed line in A represents the threshold for Disease Activity Score in 28 joints C-reactive protein (DAS28-CRP) remission (DAS28-CRP