Background In rheumatoid arthritis (RA), intensive treatment regimens aim to achieve a status of clinical remission (CR). Unfortunately, recurrent flares in RA patients in CR are not an uncommon phenomenon1. Studies with advanced imaging techniques have suggested that residual subclinical synovitis can still be present despite CR. This is of clinical relevance, because subclinical synovitis has been linked to ongoing radiological damage. Positron emission tomography (PET) can be used for sensitive detection of inflammation at molecular and cellular levels. The macrophage-binding PET tracer 11C-(R)-PK11195 enables the visualization of active arthritis in RA patients2. Moreover, 11C-(R)-PK11195 PET was able to detect subclinical arthritis in ACPA positive arthralgia patients that ultimately developed RA3.
Objectives To determine whether 11C-(R)-PK11195 PET could depict residual disease activity in early RA patients who reached CR, defined as: DAS 44 <1.6 plus no presence of tender and swollen joints, with intensive DMARD combination treatment. The second objective was to determine whether presence of residual disease activity, assessed with 11C-(R)-PK11195 PET was associated with the development of a flare (defined as presence of one or more swollen joints).
Methods 11C-(R)-PK11195 PET (HRRT, CTI/Siemens) of hands/wrists was performed in 26 RA patients who reached CR and had no clinical synovitis. 11C-(R)-PK11195 uptake (visual score: 0 (low)-3 (high)) in metacarpophalangeal, proximal interphalangeal and wrist joints (n=22 joints/patient) was scored and corrected for background uptake3. Individual joint scores were summed to obtain a cumulative PET score (range 0-66). Follow-up duration was 1 year after PET.
Results Of the included patients, 15 out of 26 (59%) developed a clinical flare of arthritis anywhere within 1 year of follow-up. 11C-(R)-PK11195 PET showed enhanced tracer uptake in at least 1 scanned joint in 12 (44%) patients. Of the 9 patients that developed a flare in the PET field of view (i.e. hands/wrists), 7 (78%) had a positive PET scan. In contrast, only 3 out of 11 patients without a flare had a positive PET scan. Cumulative PET scores of patients ranged from 0 to 8. Three patients with a cumulative PET score of 4 or higher, all developed arthritis in hands/wrists within 6 months. Cumulative PET scores of patients that developed a flare in hands/wrists (n=9) were significantly higher than those of patients that did not develop a flare (n=11) (figure 1, p=0.03).
Conclusions Baseline (R)-11C-PK11195 PET showed enhanced uptake in 44% of the patients without clinical synovitis. This might be a good indication of presence of subclinical synovitis, since 78% (7 out of 9) of the patients that developed a flare in hands/wrists within 1 year had a positive PET scan. High cumulative PET scores may be associated with short-term development of flare. Larger cohort studies are needed to confirm these data.
Molenaar et al. Arthritis & Rheumatism, 2004, 50: 36-42
van der Laken et al. Arthritis & Rheumatism, 2008, 58: 3350-5
Gent et al. Arthritis & Rheumatism, 2012, 64: 62-6
Disclosure of Interest None declared