The Rheumatoid Arthritis and MUScle (RAMUS) Study: Protocol for an observational single-arm study of skeletal muscle in patients with rheumatoid arthritis receiving tofacitinib.

People with rheumatoid arthritis (RA) are disproportionately affected by sarcopenia, the generalised loss of muscle strength and mass, consequently facing an increased risk of falls, functional decline and death. Currently, there are no approved pharmacological treatments for sarcopenia. RA patients who start tofacitinib (a Janus kinase inhibitor) develop small increases in serum creatinine that are not explained by renal function changes and could reflect sarcopenia improvement. The RAMUS Study is a proof of concept, single-arm observational study in which patients with RA who commence tofacitinib according to routine care will be offered participation according to eligibility criteria. Participants will undergo lower limb quantitative magnetic resonance imaging, whole-body dual energy x-ray absorptiometry, joint examination, muscle function testing and blood tests at three time points: prior to starting tofacitinib and 1 and 6 months afterwards. Muscle biopsy will be performed before and 6 months after starting tofacitinib. The primary outcome will be lower limb muscle volume changes following treatment initiation. The RAMUS Study will investigate whether muscle health improves following tofacitinib treatment for RA. Identifying a potential pharmacological treatment for sarcopenia could have important implications for individuals with RA and for older people in general. ISRCTN registry ID: 13364395.

Rheumatoid sarcopenia: loss of skeletal muscle strength and mass in rheumatoid arthritis.

Sarcopenia, a disorder that involves the generalized loss of skeletal muscle strength and mass, was formally recognized as a disease by its inclusion in the International Classification of Diseases in 2016. Sarcopenia typically affects older people, but younger individuals with chronic disease are also at risk. The risk of sarcopenia is high (with a prevalence of ≥25%) in individuals with rheumatoid arthritis (RA), and this rheumatoid sarcopenia is associated with increased likelihood of falls, fractures and physical disability, in addition to the burden of joint inflammation and damage. Chronic inflammation mediated by cytokines such as TNF, IL-6 and IFNγ contributes to aberrant muscle homeostasis (for instance, by exacerbating muscle protein breakdown), and results from transcriptomic studies have identified dysfunction of muscle stem cells and metabolism in RA. Progressive resistance exercise is an effective therapy for rheumatoid sarcopenia but it can be challenging or unsuitable for some individuals. The unmet need for anti-sarcopenia pharmacotherapies is great, both for people with RA and for otherwise healthy older adults.

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

BACKGROUND: Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. METHODS: Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children's Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. RESULTS: Eleven young people (5 male, median age 13 years, range 7-16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. CONCLUSIONS: IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.