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).

Keywords: Adiponectin; Body composition; Cardiovascular risk; Rheumatoid arthritis; Tocilizumab.

Conflict of interest statement

The authors have no competing interest to declare.

Figures

Fig. 1

Flow chart of the study. M, month; SAE, serious adverse event; AE, adverse event; TCZ SC, tocilizumab subcutaneous

Fig. 2

Changes in total adiponectin during tocilizumab treatment. Patients received IV tocilizumab monthly for 12 months with or without csDMARDs. They were evaluated at month M0, M1, M3, M6 and M12. The number of patients at each visit is indicated. Results are shown as mean ± SEM (paired Student’s t test: ***p = 0.0022 at month 1; *p = 0.0105 at month 3)

Fig. 3

Changes in high molecular weight (HMW) adiponectin during tocilizumab treatment. Patients received IV tocilizumab monthly for 12 months with or without csDMARDs. They were evaluated at month M0, M1, M3, M6 and M12. The number of patients at each visit is indicated. Results are shown as mean ± SEM (paired Student’s t test: ***p < 0.0001 at month 1 and p = 0.0018 at month 3; *p = 0.011 at month 6)