Cachexia in preclinical rheumatoid arthritis: Longitudinal observational study of thigh magnetic resonance imaging from osteoarthritis initiative cohort

Preclinical rheumatoid arthritis (Pre‐RA) is defined as the early stage before the development of clinical RA. While cachexia is a well‐known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre‐RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre‐RA with the matched controls. In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre‐RA and propensity score (PS)‐matched control groups. Pre‐RA was retrospectively defined as the absence of RA from baseline to year‐2, with progression to physician‐diagnosed clinical RA between years 3–8 of the follow‐up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year‐2 follow‐ups of the cohort. The outcomes were the differences between Pre‐RA and control groups in the 2‐year rate of change for thigh muscle composition [cross‐sectional area (CSA) and intramuscular adipose tissue (Intra‐MAT)] and adiposity [intermuscular adipose tissue (Inter‐MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed‐effect regression models were used for comparison. After 1:3 PS‐matching of the groups for confounding variables (demographics, risk factors, co‐morbidities, and knee osteoarthritis status), 408 thighs (102 Pre‐RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2‐year period, Pre‐RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): −180.13 mm2/2‐year, −252.80 to −107.47, P‐value < 0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre‐RA with a larger decrease in muscle CSA over 2 years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P‐values < 0.05). Comparison of changes in total adipose tissue showed no difference between Pre‐RA and control participants (estimate, 95% CI: 48.48 mm2/2‐year, −213.51 to 310.47, P‐value = 0.691). However, in the detailed analysis of thigh adiposity, Pre‐RA presence was associated with a larger increase in Inter‐MAT (estimate, 95% CI: 150.55 mm2/2‐year, 95.58 to 205.51, P‐value < 0.001). Preclinical rheumatoid arthritis is associated with a decrease in muscle cross‐sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.