MAUI, HAWAII – Recent evidence indicates that subclinical joint inflammation on ultrasound or MRI in patients having a positive cyclic citrullinated peptide antibody test but only nonspecific musculoskeletal symptoms predicts sharply increased risk of progression to full-blown diagnosable inflammatory arthritis within a matter of months. And this creates a new dilemma for rheumatologists.
The quandary is this: What are you going to do about it? After all, in the current era, the traditional treatment pyramid has been turned upside down, and early and aggressive therapy of arthritis is now recognized as best care.
“These are patients I have come back on a monthly basis instead of every 3 or 6 months. I’m hoping I’m going to be able to pick up diagnosable arthritis either by my physical exam or by the CDAI [Clinical Disease Activity Index score] or SDAI [Simplified Disease Activity Index score] so that I can initiate therapy as quickly as I possibly can to try to have a bigger impact. But I don’t initiate therapy just based on this imaging information,” Dr. Orrin M. Troum said at the 2016 Rheumatology Winter Clinical Symposium.
He highlighted two recent European studies that illustrate the prognostic power of contemporary joint imaging technologies performed at a point when patients don’t yet meet diagnostic criteria for arthritis. Both prospective studies were presented at the 2015 annual meeting of the American College of Rheumatology and have since been published.
Dr. Jackie L. Nam of the University of Leeds (England) reported on 136 consecutive anti–cyclic citrullinated peptide (anti-CCP) antibody–positive patients who presented with nonspecific musculoskeletal symptoms and no clinical synovitis. They underwent baseline ultrasound evaluation using power Doppler and grayscale imaging of 32 joints and were then prospectively followed for a median of 18.3 months.
At baseline ultrasound, 21% of patients had one or more erosions, 96% of patients had positive grayscale findings in one or more joints, and 30% were positive on power Doppler.
Forty-two percent of patients developed inflammatory arthritis after a median of 8.6 months. Patients with a baseline power Doppler score of 2 or more on a standard 0-3 scale in any joint had a 55% risk of developing inflammatory arthritis, compared with 4% if their power Doppler score was 0 or 1. A grayscale score of at least 2 was associated with a 26% likelihood of developing inflammatory arthritis, while a 0 or 1 on gray scale conferred a 3% risk. Progression to inflammatory arthritis occurred earlier in patients with a power Doppler score of 2 or 3, as well, at a median of 7.1 months (Ann Rheum Dis. 2016 Jan 22. doi: 10.1136/annrheumdis-2015-208235).
The other longitudinal study that grabbed Dr. Troum’s attention was a Dutch report on 150 patients who presented with nonspecific aches and pains. They underwent baseline serologic testing along with unilateral imaging of metacarpophalangeal, wrist, and metatarsophalangeal joints using 1.5-Tesla MRI. The imaging study was able to detect erosions as well as osteitis – that is, an inflammatory infiltrate in the bone marrow, as opposed to edema, which is watery fluid.
During a minimum of 6 months and median of 75 weeks of follow-up, 30 patients developed clinical arthritis. Twenty-six of the 30 did so before 20 weeks of follow-up had elapsed. The strongest risk factors for progression to arthritis were anti-CCP antibody positivity, with a hazard ratio of 6.4, and subclinical MRI inflammation, with a hazard ratio of 5.1.
The 1-year rate of progression to arthritis was 31% with MRI-detected subclinical inflammation alone, 71% in patients who were both MRI- and anti-CCP antibody–positive, and 3% in those who were both MRI- and anti-CCP antibody–negative (Ann Rheum Dis. 2015 Nov 27. doi: 10.1136/annrheumdis-2015-208138).
Dr. Roy Fleischmann rose from the audience to challenge Dr. Troum: Don’t these baseline imaging–positive, anti-CCP antibody–positive patients already have disease? Isn’t this the time you want to treat? he asked.
“It would ideally be the time to treat, yes,” replied Dr. Troum. “If it was me, I probably would treat myself.”
“With what, Xanax?” quipped Dr. Fleischmann of the University of Texas, Dallas.
“With methotrexate, probably,” Dr. Troum said.
He added that these were preliminary studies with relatively small numbers of patients. Before changing his practice regarding patients with these subclinical findings, he’d like to see more data and an estimate of the number needed to treat.
“It could be as many as two-thirds of the population that you’d be overtreating, people who were never going to develop anything,” Dr. Troum observed.