Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study

BMC Musculoskeletal Disorders

Manuela Le Bars^1,13  Christiane Rauch⁴  Coralie Poncet²  Melanie Chartier⁷  Karel Pavelka^1,15  Franz Rainer¹  Hans-Hartmut Peter⁹  Gerd R Burmester³  William G Bensen⁸  Michael T Nurmohamed^1,11  Dimitrios Boumpas⁵  Hanns-Martin Lorenz^1,10  Mauro Galeazzi⁶  Rieke Alten^1,12  Hubert G Nüßlein^1,14 

[1] Hospital Barmherzige Brueder, Graz, Austria;Docs International, Sèvres, France;Charité-Universitätsmedizin Berlin, Berlin, Germany;Bristol-Myers Squibb, Munich, Germany;University of Crete, Heraklion, Greece;University of Siena, Siena, Italy;Chiltern International, Neuilly, France;St. Joseph’s Hospital/McMaster University, Hamilton, Ontario, Canada;University Medical Center Freiburg, Freiburg, Germany;University Hospital Heidelberg, Heidelberg, Germany;VU University Medical Center/Jan van Breemen Research Institute, Amsterdam, The Netherlands;Schlosspark-Klinik, University Medicine, Berlin, Germany;Bristol-Myers Squibb, Rueil-Malmaison, France;University of Erlangen-Nuremberg, Nuremberg, Germany;Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic

关键词: Registries;    Safety;    Effectiveness;    Abatacept;    Biological agents;    Rheumatoid arthritis;   

Others  :  1128915
DOI  :  10.1186/1471-2474-15-14

 received in 2013-09-03, accepted in 2014-01-02,  发布年份 2014

【 摘 要 】

Background

Discontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA.

Methods

ACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve (‘first-line’) patients and patients who had previously failed treatment with at least one biologic agent (‘second-line’). Retention rates were calculated using Kaplan–Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients.

Results

Of 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%.

Conclusions

Evidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.

【 授权许可】

   
2014 Nüßlein et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]van Vollenhoven RF: Switching between anti-tumour necrosis factors: trying to get a handle on a complex issue. Ann Rheum Dis 2007, 66:849-851.
• [2]Du Pan SM, Dehler S, Ciurea A, Ziswiler HR, Gabay C, Finckh A: Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum 2009, 61:560-568.
• [3]Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ: Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 2007, 56:13-20.
• [4]Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT, Stapel S, Tak PP, Aarden L, Dijkmans B: Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum 2006, 54:711-715.
• [5]Duclos M, Gossec L, Ruyssen-Witrand A, Salliot C, Luc M, Guignard S, Dougados M: Retention rates of tumor necrosis factor blockers in daily practice in 770 rheumatic patients. J Rheumatol 2006, 33:2433-2438.
• [6]Du Pan SM, Scherer A, Gabay C, Finckh A: Differential drug retention between anti-TNF agents and alternative biological agents after inadequate response to an anti-TNF agent in rheumatoid arthritis patients. Ann Rheum Dis 2012, 71:997-999.
• [7]Caporali R, Pallavicini FB, Filippini M, Gorla R, Marchesoni A, Favalli EG, Sarzi-Puttini P, Atzeni F, Montecucco C: Treatment of rheumatoid arthritis with anti-TNF-alpha agents: a reappraisal. Autoimmun Rev 2009, 8:274-280.
• [8]Kievit W, Fransen J, Oerlemans AJ, Kuper HH, van der Laar MA, de Rooij DJ, De Gendt CM, Ronday KH, Jansen TL, van Oijen PC, Brus HL, Adang EM, van Riel PL: The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice. Ann Rheum Dis 2007, 66:1473-1478.
• [9]Emery P: Optimizing outcomes in patients with rheumatoid arthritis and an inadequate response to anti-TNF treatment. Rheumatology (Oxford) 2012, 51(Suppl 5):v22-v30.
• [10]Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R: Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006, 144:865-876.
• [11]Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechiński J, Li T, Teng J, Becker JC, Westhovens R: Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum 2008, 58:953-963.
• [12]Westhovens R, Kremer J, Emery P, Russell A, Li T, Aranda R, Becker JC, Zhao C, Dougados M: Consistent safety and sustained improvement in disease activity and treatment response over 7 years of abatacept treatment in biologic-naïve patients with RA [abstract]. Ann Rheum Dis 2009, 68(3):577. SAT0108
• [13]Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M: Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005, 353:1114-1123.
• [14]Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, Li T, Schmidely N, Le Bars M, Dougados M: 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, 67:547-554.
• [15]Mariette X, Gottenberg JE, Ravaud P, Combe B: Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatology (Oxford) 2011, 50:222-229.
• [16]Leffers HC, Ostergaard M, Glintborg B, Krogh NS, Foged H, Tarp U, Lorenzen T, Hansen A, Hansen MS, Jacobsen MS, Dreyer L, Hetland ML: Efficacy of abatacept and tocilizumab in patients with rheumatoid arthritis treated in clinical practice: results from the nationwide Danish DANBIO registry. Ann Rheum Dis 2011, 70:1216-1222.
• [17]Lindblad S, Stawiarz L, Swedish Rheumatology Quality Register: Gender and previous treatment influence outcomes from abatacept in a 5-year rheumatoid arthritis cohort [Abstract]. Ann Rheum Dis 2012, 71(3):383. FRI0205
• [18]Schiff M, Poncet C, Bars ML: Efficacy and safety of abatacept therapy for rheumatoid arthritis in routine clinical practice. Int J Clin Rheumatol 2010, 5:581-591.
• [19]Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31:315-324.
• [20]International Conference on Harmonisation: Good Clinical Practice: Consolidated Guideline; Notice of Availability, 62 Federal Register 90. 1997, 25691-25709.
• [21]Olsen J: Good Epidemiological Practice (GEP): IEA Guidelines For Proper Conduct In Epidemiologic Research. Edited by Stewart S, Pearce P, Florey C, Du V. IEA-European Federation; 2007.
• [22]D'Agostino M, Wakefield R, Berner Hammer H, Vittecoq O, Galeazzi M, Balint P, Fillipucci E, Moller I, Iagnocco A, Naredo E, Ostergaard M, Gaillez C, Kerselaers W, Van Holder K, Le Bars M: Early response to abatacept plus MTX in MTX-IR RA patients using power doppler ultrasonography: an open-label study - poster tours. Ann Rheum Dis 2012, 71(3):186. THU0095
• [23]Prevoo ML, van‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL: Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995, 38:44-48.
• [24]Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, Aletaha D, van Riel PL: Validation of the 28-joint disease activity score (DAS28) and European league against rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 2009, 68:954-960.
• [25]Aletaha D, Smolen J: The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005, 23(5 Suppl 39):S100-S108.
• [26]Dougados M, Aletaha D, van Riel P: Disease activity measures for rheumatoid arthritis. Clin Exp Rheumatol 2007, 25(5 Suppl 46):S22-S29.
• [27]Fransen J, van Riel PL: The disease activity score and the EULAR response criteria. Clin Exp Rheumatol 2005, 23(5 Suppl 39):S93-S99.
• [28]Fries JF, Spitz P, Kraines RG, Holman HR: Measurement of patient outcome in arthritis. Arthritis Rheum 1980, 23:137-145.
• [29]Wells GA, Tugwell P, Kraag GR, Baker PR, Groh J, Redelmeier DA: Minimum important difference between patients with rheumatoid arthritis: the patient's perspective. J Rheumatol 1993, 20:557-560.
• [30]Kosinski M, Zhao SZ, Dedhiya S, Osterhaus JT, Ware JE Jr: Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum 2000, 43:1478-1487.
• [31]Redelmeier DA, Lorig K: Assessing the clinical importance of symptomatic improvements. An illustration in rheumatology. Arch Intern Med 1993, 153:1337-1342.
• [32]Schiff M, Pritchard C, Huffstutter JE, Rodriguez-Valverde V, Durez P, Zhou X, Li T, Bahrt K, Kelly S, Le Bars M, Genovese MC: The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis 2009, 68:1708-1714.
• [33]Gottenberg JE, Ravaud P, Bardin T, Cantagrel A, Combe B, Dougados M, et al.: Prospective follow-Up of RA patients (1200 patient/years) treated with abatacept in real life: results from the ORA registry [abstract]. Ann Rheum Dis 2011, 70(3):466. FRI0364
• [34]Smolen JS, Aletaha D: Forget personalised medicine and focus on abating disease activity. Ann Rheum Dis 2013, 72:3-6.