Background/Purpose: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) diseases. Dyslipidemia is a known adverse reaction to tocilizumab (TCZ). TNFa blockade in RA patients has been associated with weight gain, increase in fat mass and variations in serum adipokines. Adiponectin (Adp) plays a role in the metabolism of glucose and lipids. Numerous studies have confirmed the beneficial role of Adp in insulin sensitivity and CV disease prevention, especially its high molecular weight (HMW) isoform. Increased Adp levels are associated with a reduced risk for coronary heart disease. 

Objectives:  To analyse the changes in serum adipokines and especially Adp (total and HMW) and body composition during TCZ therapy in RA.

Methods: multicenter open-label study (NCT02843789). All patients enrolled had active RA (DAS28≥ 3.2) with previous inadequate response to a csDMARDs and/or bDMARDs. They all were TCZ naïve and received TCZ IV according to the patient/physician shared decision. Patients were evaluated at baseline, 1, 3, 6, and 12 months. Clinical assessment included body mass index, waist circumference, DAS28 and HAQ scores. Laboratory parameters of inflammation (ESR, CRP, IL-6), lipid parameters (total cholesterol, LDL and HDL cholesterol, triglycerides), metabolic parameters (glycemia, insulin), serum Adp (total and HMW), leptin, resistin, and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % of fat, fat in the android and gynoid regions) was evaluated at baseline, 6, and 12 months (DEXA, Lunar GE). Our primary criteria was the changes in Adp (total and HMW) at 6 months.

Results: 107 patients (78 F; mean age ± SD: 56.6 yr ± 13.5; disease duration: 9.9 yr ± 8.1; previous biological treatment: 64.5%; corticosteroids: 69%; concomitant csDMARD: 72.8% including MTX: 61.6%) were included. 97 were still on treatment at month 6 and 77 completed the study at 12 months. Most of the patients (95%) received TCZ IV 8 mg/kg. Patients were responding to TCZ with a significant DAS28 decrease between baseline and months 6 and 12. HAQ, ESR, and CRP levels significantly decreased along the study (Table 1). Both total and HMW Adp increased from baseline to month 6 and month 12 (total Adp: baseline vs month 6: p=0.055; HMW Adp:  baseline vs month 6: p=0.02, baseline vs month 12: p=0.057).BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass (p=0.0097 at month 6 and p=0.021 at month 12). Fat mas, % of fat and android/abdominal fat did not change over the study. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia and insulin remained stable. Serum leptin, resistin and ghrelin did not change during the follow-up.

Conclusion: TCZ treatment in RA patients was associated with a significant increase in HMW Adp, increase in total Adp and also a significant gain of lean mass, while fat mass (total fat or abdominal fat) did not change. These variations in Adp during TCZ treatment may have a positive impact on the CV risk of RA patients and may contribute to the protective role of TCZ against the CV burden in RA. In addition, TCZ may have an anabolic impact on lean mass and thus on skeletal muscle.          

Table 1 ADIPRAT

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-high-molecular-weight-adiponectin-and-lean-mass-during-tocilizumab-treatment-in-patients-with-rheumatoid-arthritis-a-12-month-multicenter-study/