INSERM CIC-1431, CHU de Besançon, Centre d'Investigation Clinique Biothérapie, Pôle Recherche, 25000, Besançon, France.
Fédération Hospitalo-Universitaire INCREASE, CHU de Besançon, 25000, Besançon, France.
Arthritis Res Ther. 2020 Sep 29;22(1):224. doi: 10.1186/s13075-020-02297-7.
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.
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.
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.
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.
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).
类风湿关节炎（RA）患者患心血管疾病（CV）的风险增加。脂联素参与葡萄糖和脂质代谢，对 CV 疾病有良好的影响，尤其是其高分子量（HMW）形式。RA 存在各种表型，包括肥胖，会发生身体成分的变化。托珠单抗对 RA 患者血清脂联素和身体成分（尤其是脂肪量）的影响尚不清楚。
纳入了先前接受 csDMARDs 和/或 bDMARDs 治疗但仍处于活动期的 RA 患者，并进行了一项多中心开放标签研究。患者在基线、1、3、6 和 12 个月时进行评估。临床评估包括体重指数（BMI）和人体测量。在每个时间点测量血脂和代谢参数、血清脂联素（总脂联素和 HMW 脂联素）、瘦素、抵抗素和 ghrelin。在基线、6 和 12 个月时评估身体成分（瘦体重、脂肪量、脂肪百分比、安卓和女性区域的脂肪）。
共纳入 107 例患者。总脂联素和 HMW 脂联素自基线至 3 个月显著增加，分别在 3 个月（p=0.0105）和 1 个月（p<0.0001）达到峰值，然后逐渐下降至 6 至 12 个月并恢复至基线值。HMW 脂联素在 6 个月时仍显著升高（p=0.001）。BMI 和腰围在 6 和 12 个月时增加，6 个月时瘦体重也增加（p=0.0097）。研究期间脂肪量、脂肪百分比和安卓脂肪没有变化。血脂参数（总胆固醇和 LDL 胆固醇）增加，而血糖、胰岛素和 HOMA-IR 保持稳定。血清瘦素、抵抗素和 ghrelin 在随访期间没有变化。
托珠单抗治疗 RA 患者可显著增加总脂联素和 HMW 脂联素，尤其是在治疗开始时。托珠单抗还可显著增加瘦体重，而脂肪量没有变化。在托珠单抗治疗期间脂联素水平的这些变化可能对 RA 患者的 CV 风险产生积极影响。此外，托珠单抗可能对瘦体重/骨骼肌有合成作用。
ADIPRAT 研究是一项回顾性的 IV 期开放标签多中心研究，在 ClinicalTrials.gov 上以 NCT02843789 号注册（注册日期：2016 年 7 月 26 日）。
