Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study

Abstract Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are d...

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Main Authors: Eric Toussirot, Hubert Marotte, Denis Mulleman, Grégoire Cormier, Fabienne Coury, Philippe Gaudin, Emmanuelle Dernis, Christine Bonnet, Richard Damade, Jean-Luc Grauer, Tassadit Ait Abdesselam, Caroline Guillibert-Karras, Frédéric Lioté, Pascal Hilliquin, Antoinette Sacchi, Daniel Wendling, Benoît Le Goff, Marc Puyraveau, Gilles Dumoulin
Format: Article
Language:English
Published: BMC 2020-09-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-020-02297-7
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language English
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author Eric Toussirot
Hubert Marotte
Denis Mulleman
Grégoire Cormier
Fabienne Coury
Philippe Gaudin
Emmanuelle Dernis
Christine Bonnet
Richard Damade
Jean-Luc Grauer
Tassadit Ait Abdesselam
Caroline Guillibert-Karras
Frédéric Lioté
Pascal Hilliquin
Antoinette Sacchi
Daniel Wendling
Benoît Le Goff
Marc Puyraveau
Gilles Dumoulin
spellingShingle Eric Toussirot
Hubert Marotte
Denis Mulleman
Grégoire Cormier
Fabienne Coury
Philippe Gaudin
Emmanuelle Dernis
Christine Bonnet
Richard Damade
Jean-Luc Grauer
Tassadit Ait Abdesselam
Caroline Guillibert-Karras
Frédéric Lioté
Pascal Hilliquin
Antoinette Sacchi
Daniel Wendling
Benoît Le Goff
Marc Puyraveau
Gilles Dumoulin
Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
Arthritis Research & Therapy
Adiponectin
Cardiovascular risk
Rheumatoid arthritis
Tocilizumab
Body composition
author_facet Eric Toussirot
Hubert Marotte
Denis Mulleman
Grégoire Cormier
Fabienne Coury
Philippe Gaudin
Emmanuelle Dernis
Christine Bonnet
Richard Damade
Jean-Luc Grauer
Tassadit Ait Abdesselam
Caroline Guillibert-Karras
Frédéric Lioté
Pascal Hilliquin
Antoinette Sacchi
Daniel Wendling
Benoît Le Goff
Marc Puyraveau
Gilles Dumoulin
author_sort Eric Toussirot
title Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
title_short Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
title_full Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
title_fullStr Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
title_full_unstemmed Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
title_sort increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study
publisher BMC
series Arthritis Research & Therapy
issn 1478-6362
publishDate 2020-09-01
description Abstract Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. Methods Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. Results One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. Conclusions Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. Trial registration The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).
topic Adiponectin
Cardiovascular risk
Rheumatoid arthritis
Tocilizumab
Body composition
url http://link.springer.com/article/10.1186/s13075-020-02297-7
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spelling doaj-57fa5655c0c64ea0aba3f37d52baaf032020-11-25T03:55:47ZengBMCArthritis Research & Therapy1478-63622020-09-0122111310.1186/s13075-020-02297-7Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre studyEric Toussirot0Hubert Marotte1Denis Mulleman2Grégoire Cormier3Fabienne Coury4Philippe Gaudin5Emmanuelle Dernis6Christine Bonnet7Richard Damade8Jean-Luc Grauer9Tassadit Ait Abdesselam10Caroline Guillibert-Karras11Frédéric Lioté12Pascal Hilliquin13Antoinette Sacchi14Daniel Wendling15Benoît Le Goff16Marc Puyraveau17Gilles Dumoulin18INSERM CIC-1431, CHU de Besançon, Centre d’Investigation Clinique BiothérapieINSERM 1059, Université de Lyon, Saint-Etienne; Rhumatologie CHU de Saint-Etienne; CIC-1408, CHU de Saint-EtienneRhumatologie CHU de ToursRhumatologie Centre Hospitalier Départemental VendéeRhumatologie Hospices Civils de Lyon, INSERM UMR1033, Université Lyon 1Rhumatologie CHU de GrenobleRhumatologie Centre HospitalierRhumatologie CHU de LimogesRhumatologie Centre HospitalierRhumatologie Centre HospitalierRhumatologie Centre HospitalierRhumatologie Hôpital St JosephRhumatologie Hôpital Lariboisière AP-HP Paris, Université de ParisRhumatologie Centre Hospitalier Sud FrancilienRhumatologie Centre hospitalier Mantes la JolieCHU de Besançon, Rhumatologie, Pôle PACTE (Pathologies Aiguës Chroniques Transplantation Éducation)Rhumatologie CHU de NantesINSERM CIC-1431, CHU de Besançon, Centre d’Investigation Clinique BiothérapieLaboratoire de Biochimie Médicale, UF de Biochimie Endocrinienne et Métabolique, CHU de Besançon; EA 3920 Marqueurs pronostiques et facteurs de régulation des pathologies cardiaques et vasculaires, Université de Bourgogne Franche ComtéAbstract Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. Methods Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. Results One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. Conclusions Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. Trial registration The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).http://link.springer.com/article/10.1186/s13075-020-02297-7AdiponectinCardiovascular riskRheumatoid arthritisTocilizumabBody composition