Background Rheumatoid cachexia (RC), a phenotype of increased adiposity, reduced lean mass and insulin resistance can occur in rheumatoid arthritis (RA). It is most prevalent in those with high disease activity and is associated with increased cardiovascular morbidity and mortality. Tocilizumab (TCZ), a monoclonal anti-IL-6 antibody, successfully reduces disease activity in RA. It has also been associated with improved insulin sensitivity, increased lean mass and hyperlipidaemia. The serum concentration of myostatin, a myokine released by skeletal muscle, is increased in most disease states associated with cachexia. Moreover, its knockout and inhibition increase lean mass. However, its role in RA has not been fully elucidated.
Objectives To investigate the effect of tocilizumab treatment on serum myostatin in patients with RA.
Methods 19 patients with RA (16 female, 3 male) mean age 49.6yrs, mean DAS28 6.1, median disease duration 10yrs (range 0 to 30), mean BMI 27.4, received 13 IV infusions of TCZ 8mg/kg every four weeks as part of a 52 week, single-centre, open-label study (ACT-NEUT ). 8 had previously been exposed to a biological agent, 4 were on regular steroids, and all patients received concurrent methotrexate. Serum myostatin was measured at 0, 1, 3 and 6months of treatment using ELISA. BMI, serum lipid profile, CRP, ESR and DAS28 were measured at each visit (0, 1, 3 and 6months). Data were analysed using STATA 14. Change between 0, 3 and 6months was analysed using Wilcoxon signed rank test, statistical significance was confirmed using mixed model analysis adjusting for BMI, age and gender. Linear regression with adjustment for age, BMI and gender assessed correlation at baseline.
Results DAS28, CRP and ESR all significantly decreased with TCZ treatment. A significant increase in BMI (25.5 (IQR 21.6–31.7) vs 26.0 (IQR 21.4–32.5) p=0.0052) between baseline and 6months and serum triglycerides between baseline and 3 months (1.3 (IQR 1.3–2.2) vs 1.6 (IQR 1.3–2.6) p=0.028) was seen with TCZ. Baseline serum myostatin concentrations were negatively correlated with baseline DAS28 (r2=0.39 p=0.038). Treatment with tocilizumab for 6months resulted in a significant increase in serum myostatin from baseline (2.7ng/mL (IQR 2.0–3.1) vs 3.3ng/mL (IQR 3.0–5.0) p<0.001) [Fig. 1]. Moreover, a significant association was seen between baseline myostatin and change in cholesterol at 3 months (r2=0.51 p=0.029), when adjusting for baseline cholesterol, age, gender, BMI and change in BMI.
Conclusions We have demonstrated a significant correlation between myostatin and DAS28 and a significant change in myostatin with tocilizumab treatment. It is possible that IL-6 blockade results in a rise in myostatin. This might attenuate any improvement in muscle wasting. Future studies should measure body composition and muscle function to help understand the changes we have observed.
Wright HL, Cross AL, Edwards SW, Moots RJ. Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo. Rheumatology. 2014 Jul;53(7):1321–31.
Disclosure of Interest None declared
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