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 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).

IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis

“…Of note, participants performed supervised high-intensity interval training in the latter study [ 9 , 10 ], whereas in the current study, they performed unsupervised continuous training [ 8 ], potentially explaining the divergent findings. However, in line with the data presented herein, tocilizumab significantly increased the serum adiponectin levels in patients with rheumatoid disease [ 11 , 12 ]. Of note, no placebo controls were included in the latter studies.…”

Adipokines and Autoimmunity in Inflammatory Arthritis

“…Another study showed increased adiponectin and reduced chemerin levels in RA patients after anti-IL-6 treatment in both monotherapy or combined therapy with methotrexate independent of the treatment response [ 51 ]. Another recent study showed that tocilizumab treatment of RA patients with active RA despite previous conventional synthetic disease-modifying antirheumatoic drug (DMARD) and/or biological DMARD treatment was associated with an increase in total and HMW adiponectin, especially early after treatment onset, then declining until month 6 to 12 [ 52 ]. In this study, anti-IL-6 treatment also induced a gain in lean mass, while fat mass remained unchanged.…”

“…It was reported recently that after tocilizumab treatment for 24 weeks, resistin levels were significantly increased [ 66 , 78 ]. However, regarding anti-IL-6 treatment with tocilizumab of patients with active RA despite previous csDMARDS and/or bDMARDs, no significant changes in systemic resistin along with leptin and ghrelin during follow-up after 12 months were observed in contrast to adiponectin [ 52 ]. In addition, resistin was found not to be associated with the metabolic syndrome (by National Cholesterol Education Program’s ATP III and clinical parameters) at baseline and after one year of treatment of RA patients with DMRDs [ 63 ].…”

The Effect of TNF and Non-TNF-Targeted Biologics on Body Composition in Rheumatoid Arthritis

“…Conversely, chronic inflammation during RA is associated with persistent elevations of IL6 and insulin resistance and with an increased risk of metabolic syndrome even in patients of normal weight [ 20 ]. A few studies have investigated the effect of tocilizumab on body composition [ 4 , 21 , 22 ]. In a 1 year open follow-up study including 21 active RA patients [ 4 ], a significant increase in lean mass was observed without changes for body fat mass.…”