Preventing Muscle Wasting During Rheumatoid Arthritis Flares: A Randomised Controlled Trial

This study aims to investigate aspects of muscle health changes following a disease flare-up in people with Rheumatoid Arthritis (RA) and test potential interventions to minimise any such changes.

RA is the most common inflammatory arthritis manifesting mainly as joint swelling and pain, limiting mobility, and eventually leading to loss of functional capacity. RA also has severe extra-articular manifestations [1], affecting several tissues in the body including skeletal muscle [2]. People living with RA often present with an adverse body composition profile compared to the general population, characterised by low muscle mass at the presence of unchanged or even increased overall weight [3]. This condition, termed Rheumatoid Cachexia, may affect up to 2 out of 3 people with RA and associates with active disease, further reductions in mobility, and low quality of life [4].

While rheumatoid cachexia has been studied extensively, the course of its development, as well as potential causes or contributors to it are poorly understood. Inflammation, [5] as well as lifestyle factors, such as energy intake and physical activity, may contribute to the observed body composition changes [6].

People living with RA often experience flares of disease activity, where high levels of inflammation, cause an acute exaggeration of symptoms, leading to very low levels of mobility. This is commonly treated with corticosteroid injections which will rapidly reduce inflammation and allow the patient to regain mobility. However, that short period of high inflammatory load and low mobility may acutely affect muscle characteristics. Indeed, critically ill patients may lose up to 2% of skeletal muscle per day during the first week of hospitalisation [7]. This rapid decline in muscle health has been recently termed Acute sarcopenia (AS) by the European working group in sarcopenia and older persons (EWGSOP) [8]. Furthermore, recent work within this research team is currently under review (Aldrich et al., 2023 under review) demonstrating the rapid decline of muscle mass and quality in people suffering with various diseases. Additionally, corticosteroids themselves may further contribute to muscle wasting in RA [9]. Yet, the acute effects of flares and their treatment on muscle health in people with RA are not known.

Acute deterioration of muscle health following a flare may point towards a stepwise development of rheumatoid cachexia, i.e., bouts of acute deterioration that accumulate over time in steps rather than a continuous slow loss - which is the current understanding for the development of sarcopenia, the age-related muscle wasting. This would allow for target and potentially short-term interventions that could limit or even reverse muscle deterioration during a flare and help people with RA better maintain their functionality.