Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Efficacy, Safety and Pharmacokinetics of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis, with or without An Intravenous (IV) Loading Dose.

Nash¹, Peter T., Ludivico², Charles L., Delaet³, Ingrid, Qi³, Keqin, Murthy³, Bindu, Corbo⁴, Michael, Kaine⁵, Jeffrey L.

University of Queensland, Brisbane, Australia
East Penn Rheumatology Associates, East Stroudsburg, PA
Bristol-Myers Squibb, Princeton, NJ
Bristol-Myers Squibb (at time of study), Princeton, NJ
Sarasota Arthritis Center, Sarasota, FL

Background/Purpose:

Use of IV abatacept is well established in pts with RA. Pivotal trials of SC abatacept ± MTX have shown efficacy. Some trials included an IV abatacept loading dose to rapidly achieve therapeutic steady-state drug concentrations (C_minss>=10 mg/mL). We evaluated open-label data from two Phase III trials to examine the 3-mth efficacy and clinical pharmacokinetics (PK) of SC abatacept (125 mg/wk), with/without IV loading, in pts with established DMARD-refractory RA.

Methods:

In the initial open-label (OL) period of the ALLOW trial, pts received SC abatacept + MTX, with IV loading on Day 1 (~10 mg/kg according to weight; SC + IV load). In the OL ACCOMPANY trial, pts were stratified to SC abatacept ± MTX, with no IV load (SC only). Pts in both trials had RA refractory to biologic or non-biologic DMARDs. Data up to Mth 3 for disease activity (DAS28-CRP) and physical function (HAQ-DI) were based on pts with data available (clinically meaningful responses [CMRs] defined as reductions of >=1.2 in DAS28 and >=0.3 in HAQ-DI). PK was assessed for both trials using a validated ELISA to determine abatacept serum trough concentrations (C_min).

Results:

A total of 167 pts entered ALLOW and received SC abatacept+ IV load, 100 pts entered ACCOMPANY and received SC only (± MTX). Mean (SD) baseline demographics were generally similar between studies, although baseline disease was less severe in SC + IV versus SC only pts; tender and swollen joints were 14.3 (10.3) and 11.0 (5.7) vs 24.1 (16.2) and 17.2 (12.1), DAS28 was 4.7 (0.9) vs 5.4 (1.4) [n=98] and HAQ-DI was 1.3 (0.7) vs 1.4 (0.7) [n=99]. Mean (SD) disease duration was 7.5 (8.0) yrs vs 10.1 (11.1) yrs in SC + IV versus SC only pts, respectively. All SC + IV pts and 81% of SC only pts had previously failed MTX; 11 and 23% of pts had previously received biologics. Improvements in DAS28 and HAQ-DI were generally comparable with or without IV load (Table); CMRs were observed in both trials by <=Mth 2. By Mth 3, mean (SD) DAS28 was 3.2 (1.3) vs 3.8 (1.4) for SC + IV vs SC only, respectively, and HAQ-DI was 0.7 (0.7) vs 1.1 (0.7). Mean (SE) changes in DAS28 from baseline to Mths 1, 2 and 3 were –1.00 (0.07), –1.35 (0.08) and –1.53 (0.10) for SC + IV and –0.85 (0.11), –1.35 (0.12) and –1.57 (0.14) for SC only. Occurrence of serious adverse events, including infections, was similar with or without IV load. PK assessments indicated target therapeutic C_min was achieved by Day 15 in 88% of pts in the SC only study. C_minss concentrations were achieved by Mth 2 in both trials and remained consistent to Mth 3 (Table).

Mean percentage change from baseline (95% CI)	ALLOW (SC + IV load) DAS28 (CRP)	ACCOMPANY (SC only) HAQ-DI	DAS28 (CRP)	HAQ-DI
Month 1	-21.7 (-24.8, -18.7)	-27.3 (-32.6, -22.0)	-14.2 (-19.1, -9.3)	-21.3 (-28.7, -13.9)
	n = 165	n = 166	n = 95	n = 94
Month 2	-28.0 (-31.5, -24.6)	-37.7 (-44.7, -30.8)	-24.0 (-28.4, -19.6)	-29.8 (-37.5, -22.1)
	n = 164	n = 163	n = 96	n = 93
Month 3	-31.6 (-35.5, -27.7)	-44.6 (-51.8, -37.5)	-27.8 (-32.8, -22.9)	-32.2 (-40.4, -24.0)
	n = 161	n = 163	n = 94	n = 92

Geometric mean (CV%) of C_min (mg/mL)	ALLOW (SC + IV load)	ACCOMPANY (SC only [without MTX - with MTX])
Month 0.5 (Day 15)	Not collected	11.2 (44) - 13.7 (30)
		n = 81
Month 2	27.0 (37)	21.7 (47) - 24.4 (28)
	n = 144	n = 86
Month 3	27.6 (40) n = 132	20.4 (41) - 28.8 (37)
		n = 86
CI = confidence interval; ALLOW = Evaluation of Abatacept Administered SubcutaneousLy in AduLts With Active RheumatOid Arthritis: Impact of Withdrawal and Reintroduction on Immunogenicity, Efficacy and Safety; ACCOMPANY =A bataCept in SubjeCts with RheumatOid Arthritis AdMinistered Plus or Minus Background MTX SubcutANeouslY; SC = subcutaneous; IV = intravenous; DAS28 = Disease Activity Score 28; CRP = C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; CV = co-efficient of variation; C_min= serum trough concentration.

Conclusion:

Comparable improvements in clinical efficacy were observed over the first 3 mths, with or without IV loading. Target PK values required for efficacy were achieved in both regimens, and the majority of pts achieved therapeutic abatacept concentrations by Day 15 without IV loading. These data, although a non-comparative cross-study assessment, support the hypothesis that IV loading may not be needed to achieve desired efficacy with SC abatacept.

To cite this abstract, please use the following information:
Nash, Peter T., Ludivico, Charles L., Delaet, Ingrid, Qi, Keqin, Murthy, Bindu, Corbo, Michael, et al; Efficacy, Safety and Pharmacokinetics of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis, with or without An Intravenous (IV) Loading Dose. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :404
DOI:

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