Identifying resolution of clinically suspect arthralgia: a step towards understanding spontaneous reversal of an at-risk stage of rheumatoid arthritis.

OBJECTIVE Symptoms in the at-risk stage of clinically suspect arthralgia (CSA) can progress to Rheumatoid Arthritis (RA) or disappear spontaneously. The area of reversal of an at-risk stage is yet unexplored. Therefore, we aimed to determine its definition by evaluating patient-reported and rheumatologist-reported measures, and examine characteristics at baseline and over time of at-risk individuals with reversal. METHODS 845 consecutively included CSA-patients were followed for 2 years. Reversal was assessed as patient-reported resolution of pain (pain-score≤20 on numerical rating scale (NRS 0-100) and as resolution of CSA, as defined by the rheumatologist (clinical outcomes recorded in medical records were obtained). Clinical and functional characteristics and MRIdetected subclinical joint-inflammation were studied over time. RESULTS Among patients eligible for reversal, pain-resolution was achieved in 244/505 patients(48%) and rheumatologist-defined CSA-resolution in 357/505(71%). Patients with CSA-resolution but persistent pain, had pain from other causes than CSA/imminent-RA. Patients with pain-resolution without CSA-resolution, had remaining inflammatory symptoms (e.g. morning stiffness). Reversal of the at-risk stage was therefore best defined as rheumatologist-confirmed resolution of CSA. Patients achieving CSA-resolution had similar levels of subclinical joint-inflammation at presentation, but less pain, fatigue and morning stiffness than those without CSA-resolution. Over time, patients with CSA-resolution improved spontaneously in subclinical joint-inflammation (IRR=0.87/year, 95%CI=0.80-0.95,p=0.001) and functional disabilities (β=-0.07/year, 95%CI=-0.09 to -0.05,p<0.001). CONCLUSION Clinically, reversal of at-risk stage is better defined by rheumatologist-confirmed resolution of CSA, rather than a single patient-reported measure as pain. CSA-resolution associated with improved subclinical joint-inflammation and functional disabilities. This identification is a step towards investigating mechanisms underlying reversal of RA-risk.