Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

Tsutomu Takeuchi, Tsukasa Matsubara, Yukitomo Urata, Eiichi Suematsu, Shuji Ohta, Shigeru Honjo, Tohru Abe, Ami Yamamoto, Nobuyuki Miyasaka, Japan Abatacept Study Group, Tsutomu Takeuchi, Tsukasa Matsubara, Yukitomo Urata, Eiichi Suematsu, Shuji Ohta, Shigeru Honjo, Tohru Abe, Ami Yamamoto, Nobuyuki Miyasaka, Japan Abatacept Study Group

Abstract

Objectives: To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs.

Methods: This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed.

Results: A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years.

Conclusions: In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years.

Keywords: Japanese; abatacept; long-term study; rheumatoid arthritis.

Figures

Figure 1.
Figure 1.
Patient disposition.aDiscontinuations from adverse events included one discontinuation due to abnormal laboratory changes. bOnly 11 patients had 192 weeks of treatment at the time of analysis, due to differential enrollment times.cThe last time point for the study was 27 December 2010, at which point the median (range) cumulative duration of abatacept exposure in all patients combined was 37.7 (1.0–45.1) months. MTX, methotrexate.

References

    1. Saeki Y, Matsui T, Saisho K, Tohma S. Current treatments of rheumatoid arthritis: from the ‘NinJa’ registry. Expert Rev Clin Immunol. 2012;8((5)):455–65.
    1. Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68((7)):1100–4.
    1. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis. 2009;68((7)):1094–9.
    1. Wells AF, Westhovens R, Reed DM, Fanti L, Becker JC, Covucci A, Keystone EC. Abatacept plus methotrexate provides incremental clinical benefits versus methotrexate alone in methotrexate-naive patients with early rheumatoid arthritis who achieve radiographic nonprogression. J Rheumatol. 2011;38((11)):2362–8.
    1. Weaver AL, Lautzenheiser RL, Schiff MH, Gibofsky A, Perruquet JL, Luetkemeyer J, et al. Real-world effectiveness of select biologic and DMARD monotherapy and combination therapy in the treatment of rheumatoid arthritis: results from the RADIUS observational registry. Curr Med Res Opin. 2006;22((1)):185–98.
    1. Bulpitt KJ. Biologic therapies in rheumatoid arthritis. Curr Rheumatol Rep. 1999;1((2)):157–63.
    1. Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002;46((6)):1470–9.
    1. Bathon J, Robles M, Ximenes AC, Nayiager S, Wollenhaupt J, Durez P, et al. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis. 2011;70((11)):1949–56.
    1. Kremer JM, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Westhovens R, et al. Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial. Ann Rheum Dis. 2011;70((10)):1826–30.
    1. Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67((8)):1096–103.
    1. Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis. 2008;67((4)):547–54.
    1. Takeuchi T, Matsubara T, Nitobe T, Suematsu E, Ohta S, Honjo S, et al. Phase II dose-response study of abatacept in Japanese patients with active rheumatoid arthritis with an inadequate response to methotrexate. Mod Rheumatol. 2013;23((2)):226–35.
    1. Matsubara T, Yamana S, Tohma S, Takeuchi T, Kondo H, Kohsaka H, et al. Tolerability and efficacy of abatacept in Japanese patients with rheumatoid arthritis: a phase I study. Mod Rheumatol. 2012 Epub ahead of print: doi: 10.1007/s10165-012-0722-x.
    1. Ma Y, Lin BR, Lin B, Hou S, Qian WZ, Li J, et al. Pharmacokinetics of CTLA4Ig fusion protein in healthy volunteers and patients with rheumatoid arthritis. Acta Pharmacol Sin. 2009;30((3)):364–71.
    1. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31((3)):315–24.
    1. Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992;35((5)):498–502.
    1. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38((6)):727–35.
    1. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23((2)):137–45.
    1. Westhovens R, Kremer JM, Moreland LW, Emery P, Russell AS, Li T, et al. Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study. J Rheumatol. 2009;36((4)):736–42.
    1. Genovese MC, Schiff M, Luggen M, Le Bars M, Aranda R, Elegbe A, Dougados M. Longterm safety and efficacy of abatacept through 5 years of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitor therapy. J Rheumatol. 2012;39((8)):1546–54.
    1. Buch MH, Boyle DL, Rosengren S, Saleem B, Reece RJ, Rhodes LA, et al. Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study. Ann Rheum Dis. 2009;68((7)):1220–7.
    1. Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, et al. Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006;33((11)):2162–6.
    1. Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, et al. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial) Ann Rheum Dis. 2010;69((3)):510–6.
    1. Buch MH, Aletaha D, Emery P, Smolen J. Reporting of long-term extension studies: lack of consistency calls for consensus. Ann Rheum Dis. 2011;70((6)):886–90.

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