Background Early in the course of rheumatoid arthritis (RA), joint damage progresses rapidly, and halting this progression is a major treatment goal. Individual joints are believed to be unequally impacted by disease progression, but little data have been available in this regard.
Objectives To evaluate radiographic progression in individual joints of patients with early RA, before and after treatment with methotrexate (MTX) -/+ adalimumab (ADA), over a 2-year time period.
Methods PREMIER was a phase 3, randomized, placebo-controlled, 104-week trial conducted in MTX-naïve patients with early RA (<3 years), who were allocated to 1 of 3 treatments: MTX (N=257), ADA (N=274), or ADA+MTX (N=268). Radiologists blindly assessed erosions (E) and joint space narrowing (JSN) in 22 and 20 joints, respectively, of hands, wrists, and feet at baseline and weeks 26, 52, and 104, by the total Sharp scoring method. This analysis included all pre-treatment (baseline) radiographic data and compared post-baseline data in patients receiving MTX vs ADA+MTX. Logistic modeling was used to characterize dependence of 1) baseline E/JSN damage on RA disease duration and 2) progression at week 52 on treatment after adjusting for baseline disease duration.
Results At baseline (mean RA duration =0.8 years), radiographic data for 790 patients were available; E were more prevalent than JSN, with 8/22 vs 0/20 joints damaged in ≥50% of patients. The odds of E and JSN significantly increased with longer baseline RA duration in the majority of joints (P <0.05 for 17/22 joints for E and 15/20 joints for JSN). However, in the proximal interphalangeal (PIP) joints, JSN was more prevalent at an early stage of disease and changed little over time, in contrast to the pattern evident in other joints. Systematic progression of E and JSN was measurable through 104 weeks in MTX-treated patients but less apparent in ADA+MTX-treated patients, irrespective of baseline disease duration. Following adjustment for disease duration, 19/22 joints demonstrated significantly higher odds for progressive E at week 52 with MTX treatment vs ADA+MTX, as did 10/20 joints for JSN. In general, progression of E and JSN was more apparent in patients at an earlier stage of disease than in those with longer disease duration, although the slopes of the curves generally were lower in the ADA+MTX group.
Conclusions Although both prevalence and extent of damage in individual joints were higher in patients with longer disease duration at baseline, further progression of E and JSN was more pronounced in those with early disease, supporting the concept of early, aggressive treatment for prevention of future disability. Irrespective of disease duration at the time of treatment initiation, ADA+MTX combination therapy significantly prevented progression of E and JSN in the majority of assessed joints compared with MTX. Data also demonstrated that erosive damage (E) typically preceded JSN in most joints, although this was reversed in the PIP joints, suggesting a varied pathology across different anatomical locations. Overall, these results confirm a measurable, reproducible, “typical” pattern of progressive radiographic joint damage across a population with early, active RA.
Acknowledgements AbbVie Inc. sponsored the study (NCT00195663), contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. Medical writing support was provided by Benjamin Wolfe, PhD, of AbbVie Inc.
Disclosure of Interest V. Strand Consultant for: AbbVie Inc., S. Liu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., N. Mozaffarian Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.