Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

Abstract

Background: The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA).

Methods: This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression.

Results: Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression.

Conclusions: MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures.

Trial registration: ClinicalTrials.gov, NCT01164579 .

Keywords: Bone erosion; Disease activity; Joint space narrowing; Osteitis; Predictive ability; RAMRIQ; RAMRIS; Radiographic progression; Rheumatoid arthritis; Synovitis.

Conflict of interest statement

PGC has been a consultant for AbbVie, Eli Lilly, Flexion, GlaxoSmithKline, Novartis, Pfizer Inc and Roche, and has been a member of the speakers’ bureau for AbbVie, Novartis and Roche. MØ has received grants or research support from AbbVie, Centocor and Merck, and has been a consultant and/or a member of the speakers’ bureau for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB and Wyeth. OT has been a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Horizon, Lilly and Pfizer Inc, has been a member of the speakers’ bureau for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Horizon, Novartis, Pfizer Inc, Sanofi-Genzyme and Takeda, and has received grants or research support from AbbVie, Amgen, Bristol-Myers Squibb, Centocor, Corrona, Novartis and Pfizer Inc. MAB is an employee of Imorphics Ltd, a wholly owned subsidiary of Stryker Corp. GG was an employee of Imorphics Ltd, a wholly owned subsidiary of Stryker Corp, at the time the research was conducted. AS is an employee of IQVIA Inc and has acted as a paid consultant to Pfizer Inc in connection with analysis of study data. BW and AK were employees of Pfizer Inc at the time the research was conducted. ZX, JA and DC are employees and shareholders of Pfizer Inc.