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

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

Maria-Antonietta D'Agostino  1 , Rieke Alten  2 , Eduardo Mysler  3 , Manuela Le Bars  4 , June Ye  5 , Bindu Murthy  5 , Julia Heitzmann  6 , Radu Vadanici  4 , Gianfranco Ferraccioli  7
Affiliations
Clinical Trial

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

Maria-Antonietta D'Agostino et al. Clin Rheumatol. 2017 Dec.

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.

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Conflict of interest statement

Disclosures

Prof. D’Agostino has received speaker’s bureau fees from Bristol-Myers Squibb, AbbVie, and Novartis, as well as research grants from Pfizer. Prof. Alten has received research grants, consulting fees, and speaker’s bureau fees from Bristol-Myers Squibb. Dr. Mysler has received research grants and speaker’s bureau fees from Bristol-Myers Squibb, Roche, Eli Lilly, AbbVie, Novartis, Janssen, and Pfizer. Dr. Le Bars and Dr. Murthy are shareholders and employees of Bristol-Myers Squibb. Dr. Ye and Dr. Vadanici are employees of Bristol-Myers Squibb. Julia Heitzmann is an employee of Excelya and a paid consultant for Bristol-Myers Squibb. Prof. Ferraccioli has received grant support from Roche and Bristol-Myers Squibb and speaker fees from Roche, Bristol-Myers Squibb, AbbVie, Pfizer, UCB, MSD, Eli Lilly, Novartis, and GlaxoSmithKline.

Funding

This study was sponsored by Bristol-Myers Squibb.

Figures

Fig. 1
Fig. 1
Proportions of patients receiving subcutaneous (SC) or intravenous (IV) abatacept achieving Disease Activity Score 28 (DAS28; C-reactive protein) remission over 6 months by baseline body mass index in a the separate analyses and b the pooled analysis by route of abatacept administration. As-observed analysis in the intent-to-treat population (> 90% of patients reached the final observation at day 169). Error bars represent 95% confidence intervals
Fig. 2
Fig. 2
Proportions of patients receiving subcutaneous (SC) or intravenous (IV) abatacept achieving Simplified Disease Activity Index (SDAI) remission over 6 months by baseline body mass index in a separate analyses and b the pooled analysis by route of abatacept administration. As-observed analysis in the intent-to-treat population (> 90% of patients reached the final observation at day 169). Error bars represent 95% confidence intervals
Fig. 3
Fig. 3
Proportions of patients receiving subcutaneous or intravenous abatacept achieving Clinical Disease Activity Index remission over 6 months by baseline body mass index in a the separate analyses and b the pooled analysis by route of abatacept administration. As-observed analysis in the intent-to-treat population (> 90% of patients reached the final observation at day 169). Error bars represent 95% confidence intervals
Fig. 4
Fig. 4
Minimum plasma concentrations (Cmin) of abatacept (ABA) at month 3 (day 85) and month 6 (day 169) by baseline body mass index (BMI) in patients receiving subcutaneous (SC) or intravenous (IV) abatacept *10 μg/mL. Bottom and top of box = first and third quartiles; band inside box = median; ends of whiskers = last observed value within 1.5 times the interquartile range; diamond = mean Cmin > 10 μg/mL is associated with near-maximal efficacy
See this image and copyright information in PMC

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