Body mass index and clinical response to intravenous or subcutaneous abatacept in patients with rheumatoid arthritis

Clin Rheumatol. 2017 Dec;36(12):2655-2665. doi: 10.1007/s10067-017-3788-1. Epub 2017 Aug 18.

Abstract

This post hoc analysis of ACQUIRE (NCT00559585) explored the effect of baseline body mass index (BMI) on the pharmacokinetics of and clinical response to subcutaneous (SC) or intravenous (IV) abatacept in patients with rheumatoid arthritis (RA). ACQUIRE was a phase 3b, 6-month, double-blind, double-dummy study in which patients with RA were randomized (1:1) to SC (fixed - dose; 125 mg/week) or IV (weight-tiered; ~ 10 mg/kg/month) abatacept plus methotrexate. In this analysis, minimum abatacept plasma concentration (Cmin) was measured at 3 and 6 months, and clinical remission over 6 months was assessed by Disease Activity Score 28 (C-reactive protein; DAS28 [CRP], < 2.6), Simplified Disease Activity Index (SDAI, ≤ 3.3), and Clinical Disease Activity Index (CDAI, ≤ 2.8). Data were stratified by baseline BMI (underweight/normal, < 25 kg/m2; overweight, 25 to < 30 kg/m2; obese, ≥ 30 kg/m2) and administration route. Of the 1456/1457 patients for whom baseline BMIs were available, 526 (36%; SC 265, IV 261) patients were underweight/normal, 497 (34%; SC 249, IV 248) were overweight, and 433 (30%; SC 221, IV 212) were obese. Median Cmin abatacept concentration was ≥ 10 μg/mL (efficacy threshold) at 3 and 6 months in > 90% of patients across BMI groups with both administration routes. DAS28 (CRP), SDAI, and CDAI remission rates at 6 months were similar across BMI groups and 95% confidence intervals overlapped at all time points in both separate and pooled SC/IV analyses. Therapeutic concentrations of abatacept and clinical remission rates using stringent criteria were similar across patient BMIs and administration routes.

Keywords: Body mass index; DAS28; Disease activity; Pharmacokinetics; Rheumatoid arthritis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Abatacept / administration & dosage
  • Abatacept / therapeutic use*
  • Adult
  • Aged
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Body Mass Index*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Abatacept
  • Methotrexate