Rheumatoid cachexia in rheumatoid arthritis patients treated in the current treat-to-target era: An exploration of the incidence, mechanisms, effects on physical function, and a potential nutritional treatment

Rheumatoid cachexia (RC), i.e. muscle wasting and adiposity gain in rheumatoid arthritis (RA), is driven by inflammation and is a major contributor to reduced strength and physical function. Current treatment for RA is based on approaches that aim to tightly control inflammation from diagnosis onwards. This is best exemplified by ‘treat-to-target’ (T2T), which targets low disease activity, preferably ‘clinical remission’. The success of T2T in controlling inflammation is well-established, but whether it has attenuated RC is unknown. In a cross-sectional trial, we demonstrated that, despite well controlled disease activity, RC and substantially impaired physical function was still present in patients treated by T2T. Consequently, adjunct interventions are required to restore body composition and function. Nutritional creatine (Cr) supplementation may provide a safe and easy means of improving muscle mass and physical function. In a randomised control trial, 12 weeks Cr supplementation significantly increased muscle mass, but was unable to improve objective measures of physical function. To investigate their associations with body composition, using serum from RA patients with: treated versus untreated disease; patients versus healthy controls; and patients before and after anabolic interventions (PRT or Cr supplementation), we were unable to identify serum biomarkers (i.e. tumor necrosis factor (TNF)-α, soluble TNF-α receptor-I, interleukin-6, insulin-like growth factor (IGF)-1, IGF-binding protein 3, myostatin, adiponectin, and leptin) for RC. Following an unexpected, and substantial, loss of muscle mass in a patient in our Cr supplementation trial, we investigated and identified a probable catabolic effect of intramuscular (IM) corticosteroid (CS) injections used to treat active disease. Preliminary findings from an ongoing study revealed significant muscle loss in all five RA patients tested within 4 weeks of IM CS injection to treat a disease flare. These findings raise concerns about this routine and recommended treatment, and provide a further potential mechanism for RC