Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis.
BACKGROUND
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA.


METHODS
Twenty-one active RA patients treated with TCZ were included in a 1 year open follow-up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non-RA controls matched for age, sex, body mass index, and metabolic syndrome.


RESULTS
Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut-off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed.


CONCLUSIONS
Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat distribution was observed. In contrast, muscle gain suggests that blocking IL-6 might be efficient in treating sarcopaenia associated with RA.
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.|UNH-UMR 1019, INRA, University Clermont Auvergne, 58 rue Montalembert, BP 321, 63009, Clermont-Ferrand CEDEX, France.
Anne
A
Tournadre
Biostatistics Unit (DRCI), CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.
Bruno
B
Pereira
Department of Preventive and Occupational Medicine, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.|Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions EA3533, University Clermont Auvergne, CNRS LaPSCo, Physiological and Psychosocial Stress, 24 Avenue des Landais, 63171, Aubière, France.|Faculty of Health, Australian Catholic University, Melbourne, Victoria, Australia.
Fréderic
F
Dutheil
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.
Charlotte
C
Giraud
Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions EA3533, University Clermont Auvergne, CNRS LaPSCo, Physiological and Psychosocial Stress, 24 Avenue des Landais, 63171, Aubière, France.|Faculty of Health, Australian Catholic University, Melbourne, Victoria, Australia.
Daniel
D
Courteix
Biochemistry and Molecular Biology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.|University Clermont Auvergne, EA7281, 28 Place Henri-Dunant, 63001, Clermont-Ferrand, France.
Vincent
V
Sapin
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.
Thomas
T
Frayssac
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.
Sylvain
S
Mathieu
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.
Sandrine
S
Malochet-Guinamand
Rheumatology Department, CHU Clermont-Ferrand, 58 rue Montalembert, BP 69, 63003, Clermont-Ferrand CEDEX, France.|UNH-UMR 1019, INRA, University Clermont Auvergne, 58 rue Montalembert, BP 321, 63009, Clermont-Ferrand CEDEX, France.
Martin
M
Soubrier
D015502:Absorptiometry, Photon; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D001823:Body Composition / Q000187:drug effects*; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000453:epidemiology; D055442:Metabolome / Q000187:drug effects*; D008875:Middle Aged; D000093242:Interleukin-6 Inhibitors
D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C502936:tocilizumab
Cachexia; Metabolic change; Rheumatoid arthritis; Sarcopaenia; Tocilizumab