MRI in Rheumatoid Arthritis: Assessing Disease Activity, Remission, Prognosis

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MRI shows promise in early detection and prognosis of RA, as a potential surrogate marker for disease activity, and as a more accurate measure of remission.
MRI shows promise in early detection and prognosis of RA, as a potential surrogate marker for disease activity, and as a more accurate measure of remission.

Magnetic resonance imaging (MRI) shows changes in bone and cartilage and can discriminate these from fluid and soft tissue around the joints, making it a good technique to measure synovial volume and inflammation characteristic of rheumatoid arthritis (RA).1 The use of T2-weighted images identifies structures with high water content clearly, and regions of high vascularity are further delineated by injection of gadolinium contrast. The combined evidence from studies over the past decade has suggested an extensive role for MRI in the management of RA.

Evidence From MRI Studies

Relationships between bone marrow edema (BME) and synovitis in RA have been well established.2 Divergent findings have emerged from more recent MRI studies that questioned earlier beliefs that the relationship between synovitis and BME was the primary cause of bone erosion and that synovial pathways were fundamental to the initiation of BME, erosions, or thinning of cartilage. More recent MRI studies suggest multiple separate etiologies that are more likely to be independent risk factors for RA degeneration:

  • A 2003 study indicated that bone damage tended to occur on the radial side of joints, generally driven by early joint inflammation originating there, supporting a biomechanical mechanism underlying erosive progression in RA.2
  • MRI studies have since revealed that BME is an early event in RA and that cartilage thinning occurs as a later process, although radiographic studies did not support a relationship between the two.3,4
  • A 2011 investigation showed that erosion and joint space narrowing are consequences of inflammation in RA that may develop simultaneously in different joints.4
  • A 2014 study indicated that cartilage damage progression is triggered by the cartilage damage pathways, not by osteitis and synovitis.5

Using MRI to Measure Disease Activity

Static gadolinium-enhancing imaging protocols can be used to quantify the volume of synovitis, although dynamic contrast-enhanced sequential images may better capture local synovial inflammation.6 Although a clear mechanism between histopathologic inflammation and MRI synovitis has not been established, substantial evidence supports an important role for the synovial pathway in the pathobiology of joint damage:

  • MRI stands out from other modalities for its ability to characterize BME clearly. BME has been equated with histologic osteitis and signals the presence of synovitis.
  • Combining MRI data with knowledge of synovial pathobiology may be used to identify signatures of bone erosion in RA.
  • MRI can be used as an alternative to standard radiographs to detect bone cartilage loss.

Prognostic Uses for MRI

The superior ability of MRI to detect early features of RA, including synovitis, BME, continuing bone erosions, and the later appearance of cartilage thinning, points to prognostic utility of the technique. Bone erosions have been detected with MRI up to 2 years earlier than with conventional radiographs, and it has shown high sensitivity at detecting change among smaller cohorts.7

A primary feature of RA is the development of erosions of the hands or wrists, which have been shown by annual radiologic scores to increase by as much as 1.9%. A review found that erosions emerge early (by 5 years) in 39% to 73% of patients with RA, and that 43% of patients reach maximum damage levels by 20 years.8

The authors of a 2013 study wrote, “Disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA.”9

Ultrasound gray-scale inflammation, MRI synovitis, and MRI BME were all independently predictive of RA outcomes in a 2009 study of 84 patients.10 A group trend towards higher MRI synovitis scores and 3-month radiographic radiogrammetry bone mineral density loss in patients in whom MRI erosions developed was also observed. Imaging alone was not sufficient to predict outcomes.

MRI-Detected Remission

Mounting evidence suggests MRI as a surrogate marker for histopathologic synovitis following therapeutic intervention, based on the consistent relationship demonstrated between CD68+ sublining macrophage number (the only known reliable biomarker for RA degeneration) and MRI synovitis.1

Another study found MRI superior to Disease Activity Score (DAS)28 or European League of Associations for Rheumatology (EULAR) standards. Using EULAR guidelines, progressive erosive disease was detected on MRI in 40% of patients who had documented remission.11 ”Future studies are needed to determine the prognostic clinical impact of disease progression in MRI despite clinical remission, and to investigate if DAS28 remission may be an insufficient therapeutic goal and should be accompanied by MRI remission criteria,” the authors wrote.

Conclusion

MRI shows promise in early detection and prognosis of RA, as a potential surrogate marker for disease activity, and as a more accurate measure of remission. Before this potential can be reached, however, there is a need to “validate the relationship between synovial pathobiology and MRI abnormalities at the single joint level both in well-defined early and established RA cohorts and within clinical trial protocols of established and novel biologic drugs.”

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References

  1. Humby F, Mahto A, Ahmed M, et al. The relationship between synovial pathobiology and magnetic resonance imaging abnormalities in rheumatoid arthritis: a systematic review. J Rheumatol. 2017;44(9):1311-1324.
  2. Tan AL, Tanner SF, Conaghan PG, et al. Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis. Arthritis Rheum. 2003;48(5):1214-1222.
  3. McQueen F, Clarke A, McHaffie A, et al. Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring system. Ann Rheum Dis. 2010;69(11):1971-1975.
  4. van der Heijde D. Erosions versus joint space narrowing in rheumatoid arthritis: what do we know? Ann Rheum Dis. 2011;70:i116-118.
  5. McQueen FM, McHaffie A, Clarke A, et al. MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI study examining cartilage damage. Arthritis Res Ther. 2014;16(1):R33.
  6. Reece RJ, Kraan MC, Radjenovic A, et al. Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging. Arthritis Rheum. 2002;46(2):366-372.
  7. Østergaard M, Hansen M, Stoltenberg M, et al. New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier. Arthritis Rheum. 2003;48(8):2128-2131.
  8. Scott DL, Smith C, Kingsley G. Joint damage and disability in rheumatoid arthritis: an updated systematic review. Clin Exp Rheumatol. 2003;21:S20-S27.
  9. Nair SC, Bijlsma JW, van der Werf JH, et al. Do radiographic joint damage and disease activity influence functional disability through different mechanisms? Direct and indirect effects of disease activity in established rheumatoid arthritis. J Rheumatol. 2013;40(9):1505-1512.
  10. Bøyesen P, Haavardsholm EA, van der Heijde D, et al. Prediction of MRI erosive progression: a comparison of modern imaging modalities in early rheumatoid arthritis patients. Ann Rheum Dis. 2011;70(1):176-179.
  11. Sewerin P, Vordenbaeumen S, Hoyer A, et al. Silent progression in patients with rheumatoid arthritis: is DAS28 remission an insufficient goal in RA? Results from the German Remission-plus cohort. BMC Musculoskelet Disord. 2017;18(1):163.
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