Identifying Resolution of Clinically Suspect Arthralgia: A Step Toward 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 We followed 845 consecutively included patients with CSA for 2 years. Reversal was assessed as patient-reported resolution of pain (pain score ≤ 20 on a 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 magnetic resonance imaging (MRI)-detected 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 causes other than CSA or imminent RA. Patients with pain resolution without CSA resolution had remaining inflammatory symptoms (eg, 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 (incidence rate ratio 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 such as pain. CSA resolution was associated with improved subclinical joint inflammation and functional disabilities. This identification is a step toward investigating mechanisms underlying reversal of RA risk.