Don't Stop RA Treatment at Remission: Inflammation Outlasts It

Ranganath VK, Motamedi K, Haavardsholm E, et al.,Comprehensive appraisal of MRI findings in sustained RA remission: Sub-study of the TEAR trial. Arthritis Care & Resarch. 2015;Accepted manuscript.  doi: 10.1002/acr.22541

Early rheumatoid arthritis (RA) patients in sustained remission after 2 years of aggressive therapy-triple therapy or a tumor necrosis-alpha (TNFα) blocker plus methotrexate (MTX)-still show evidence of joint inflammation, according to follow-up data from a randomized, double-blind clinical trial.

Magnetic resonance imaging (MRI) from 118 seropositive patients who [[{"type":"media","view_mode":"media_crop","fid":"31845","attributes":{"alt":"rheumatoid arthritis","class":"media-image media-image-right","id":"media_crop_2599270644524","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3360","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 149px; height: 145px; margin: 3px; float: right;","title":"","typeof":"foaf:Image"}}]]completed the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial show residual joint inflammation in all of them and osteitis in a majority.  Only 29, however, had symptoms such as pain or swelling.  

Seropositive RA-rheumatoid factor or ACPA (anticitrullinated peptide antibody)-are also associated with more severe disease.

Some studies suggest that RA treatment may be discontinued among patients showing sustained remission with sensitive imaging -- MRI or ultrasound (US) -- but these new results show that may not always be advisable, the authors say.

The TEAR sub-study also provides new evidence that imaging can uncover synovitis and bone damage that suggests future risk among RA patients in remission.

A 2014 meta-analysis of ultrasound studies conducted among more than 1,600 patients (most of them in remission) over an 11-year period found that 80% showed joint inflammation on grayscale US and 44% showed synovitis on power Doppler US, with increased odds for relapse and structural progression.

In the current study, 118 TEAR trial patients (the vast majority seropositive white women with a mean age of 51) had contrast-enhanced MRI of the most-involved wrist. Two readers scored the images for synovitis, osteitis, tenosynovitis, and erosions.

None of the patients had an MRI score of zero for synovitis or erosions. While only 16% of patients had radiographic progression over the 2-year period, 78% showed evidence of osteitis on MRI, a harbinger of future progression.

MRI scores were statistically lower among patients who met the strictest criteria for remission -- the 2011 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria and remission by Chronic Disease Activity Index (CDAI).

Total MRI Inflammatory Scores were lower among patients in clinical remission and correlated with longer duration of remission (a year or more).

However, there were no statistically significant differences in total MRI scores between patients treated with triple therapy-MTX plus sulfasalazine and hydrochloroquine-or with a TNF blocker (etanercept) paired with MTX.

Despite small numbers and short followup, the authors caution prudence in changing drug regimens after remission.

“It is still unclear whether attainment of clinical remission justifies the promotion of drug holidays or cessation of RA treatment,” they conclude. Given the high rates of osteitis in this study plus "strong prior published data" suggesting that osteitis predicts future progression, it is "currently ill-advised to discontinue therapy until future studies suggest otherwise.”