Real-World Efficacy and Safety of Abatacept Treatment for Rheumatoid Arthritis: 12-Month Interim Analysis of the Action Study

H. Nüßlein¹, R. Alten², M. Galeazzi³, H. M. Lorenz⁴, Dimitrios Boumpas⁵, M. T. Nurmohamed⁶, W. Bensen⁷, Gerd Burmester⁸, H.-H. Peter⁹, F. Rainer¹⁰, Karel Pavelka¹¹, M. Chartier¹², C. Poncet¹³, C. Rauch¹⁴ and M. Le Bars¹⁵, ¹University Erlangen, Nürnberg, Germany, ²Schlosspark-Klinik, University Medicine, Berlin, Germany, ³University of Siena, Siena, Italy, ⁴University Hospital Heidelberg, Heidelberg, Germany, ⁵Panepistimio Kritis, Rethymnon, Greece, ⁶VU University Medical Center/Jan van Bremen Research Institute, Amsterdam, Netherlands, ⁷St. Joseph's Hospital and McMaster University, Hamilton, ON, Canada, ⁸Charité-Universitätsmedizin, Berlin, Germany, ⁹University Medical Center Freiburg, Freiburg, Germany, ¹⁰Hospital Barmherzige Brueder, Graz, Austria, ¹¹Institute of Rheumatology, Prague, Czech Republic, ¹²Chiltern International, Neuilly, France, ¹³Docs International, Sévres, France, ¹⁴Bristol-Myers Squibb, Munich, Germany, ¹⁵Bristol-Myers Squibb, Rueil Malmaison, France

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Abatacept, clinical trials and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose: Randomized controlled trials (RCTs) of abatacept (ABA) in patients (pts) with RA have demonstrated sustained, long-term efficacy, high pt retention, and consistent safety.¹ Data from the clinical setting can determine if benefits translate into the real world. We evaluate 1-yr retention, efficacy and safety of ABA in RA pts treated in routine clinical practice (according to label at time of enrollment) in Europe and Canada. Methods: AbataCepT In rOutiNe clinical practice (ACTION) is an ongoing, non-interventional, prospective cohort of ABA-treated RA pts with inadequate response to MTX or anti-TNF therapy in Europe and Canada, initiated Mar 2008.² At data cut-off in Feb 2012, all pts had reached 1-yr follow-up. Retention rate (Kaplan–Meier estimate) and disease activity (EULAR response) are reported over 12 mths for pts on treatment and with available data, according to whether pts received ABA as a first biologic, or after failure of 1 or ≥2 anti-TNFs. Safety is reported for all enrolled pts, up to data cut-off.

Results: 1138 pts were enrolled and 1120 were evaluable. 1000 (89.3%) had previously failed on biologic treatment, 982/1000 (98.2%) of whom failed ≥1 anti-TNF agent. 120 (10.7%) had not received biologic treatment prior to ABA initiation. Baseline characteristics for the three groups are shown in the Table. Retention rates, reasons for discontinuation and % moderate and good EULAR responders at Mth 12 are presented for ABA when used as the first biologic, first switch agent, and after ≥2 anti-TNFs, and suggest that earlier usage results in higher pt retention (Table). 106 serious adverse events were reported in 60/1138 (5.3%) pts (21 discontinuations). 11 deaths were reported, including 3 due to serious infections (sepsis [4 mths after last ABA infusion; pt was receiving tocilizumab]; Pneumocystis jiroveci [4 mths after last ABA infusion, pt had deep vein thrombosis]; and urosepsis) unrelated to ABA. 23 pts experienced serious infections; 9 malignancies; 5 serious cardiac disorders; and 3 serious vascular disorders. No TB occurred, two opportunistic infections were reported (cytomegalovirus and P. jiroveci).

Conclusion: This large-scale, international, observational real-life study showed that the use of ABA as the first biologic in MTX-inadequate responders, or after first or later switching from anti-TNFs, was associated with good pt retention over 12 mths, particularly when used earlier in the course of treatment. ABA was clinically effective and well tolerated. These data are consistent with previous RCT findings,^1,3 and national registry data for biologics.^4-6 1. Genovese M, et al. N Engl J Med 2005;353:1114–23 2. Nüßlein H, et al. Ann Rheum Dis 2011;70(Suppl 3):464 3. Kremer JM, et al. Ann Intern Med 2006;144:865–76 4. Leffers HC, et al. Ann Rheum Dis 2011;70:1216–22 5. Gomez-Reino J, et al. Arthritis Res Ther 2006;8:R29 6. Lindblad S, et al. Ann Rheum Dis 2012;71(Suppl 3):383

Baseline characteristics	ABA first biologic n=120	ABA first switch (1 previous anti-TNF) n=481	ABA after ≥2 previous anti-TNFs n=501
Mean age (SD), years	59.0 (13.8), n=120	56.2 (12.4), n=481	56.0 (12.4), n=501
Mean RA duration (SD), years	7.0 (7.8), n=118	9.8 (8.0), n=465	13.1 (9.4), n=484
≥1 CV risk or comorbidity, n (%)	86 (71.7%), n=120	336 (69.9%), n=481	365 (72.9%), n=501
Mth 12 outcomes
Retention, Kaplan–Meier estimate (95% CI)	83.6% (74.9, 89.5)	73.2% (68.8, 77.2)	64.1% (59.5, 68.4)
Discontinuation for lack of efficacy, n (%)	11 (9.2%), n=120	75 (15.6%), n=481	101 (20.2%), n=501
Discontinuation for intolerance, n (%)	3 (2.5%), n=120	11 (2.3%), n=481	15 (3.0%), n=501
Good EULAR response	34.5%, n=29	34.5%, n=194	27.3%, n=165
Moderate EULAR response	37.9%, n=29	41.8%, n=194	45.5%, n=165
EULAR response criteria: Moderate/good=DAS28 improvement of ≥0.6 and a DAS28 of ≤5.1; Good=DAS28 improvement of >1.2 and a DAS28 of <3.2; Moderate=DAS28 improvement of >1.2 and a DAS28 of ≥3.2, or DAS28 improvement of 0.6–1.2 and a DAS28 of ≤5.1

Disclosure:

H. Nüßlein,

Bristol-Myers Squibb,

R. Alten,

Abbott, Bristol Myers-Squibb, Novartis, Pfizer, UCB,

M. Galeazzi,
None;

H. M. Lorenz,

BMS, Abbott, MSD, Pfizer, UCB, Roche, GSK, Medac, Chugai, Novartis, Sanofi Aventis,

D. Boumpas,
None;

M. T. Nurmohamed,

MBS, MSD, Roche, Abbott, Pfizer and UCB,

W. Bensen,

Abbott, Amgen, Bristol Myers Squibb, Janssen, Merck-Schering, Lilly, Novartis, Pfizer, Wyeth, Proctor and Gamble, Roche, Sanofi, Servier, Aventis, UCB, Warner Chilcott,

G. Burmester,

Abbott, BMS, MSD, Pfizer, Roche, MSD,

H. H. Peter,
None;

F. Rainer,
None;

K. Pavelka,

Abbott, Roche, Pfizer, UCB, BMS, Sanofi Aventis,

Abbott, Roche, Pfizer, UCB,

M. Chartier,
None;

C. Poncet,
None;

C. Rauch,

BMS,

M. Le Bars,

Bristol-Myers Squibb,

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