Alten, Rieke

Chartier, Melanie

Elbez, Yedid

Fusaro, Enrico

Galeazzi, Mauro

Le Bars, Manuela

Lorenz, Hanns-Martin

Muratore, Maurizio

Nüßlein, Hubert G

Pagano Mariano, Giuseppa

Patanè, Giovanni

Nüßlein, Hubert G

Patanè, Giovanni

Archivio della Ricerca - Università degli Studi di Siena

935Clinical and Experimental Rheumatology 2018Letters to the EditorsRetention and clinical response to abatacept in patients with rheumatoid arthritis: an Italian perspectiveSirs,Country differences are important con-siderations when assessing the impact of patient characteristics on clinical response to anti-rheumatic drugs (1). In Italy, the proportion of people aged ≥65 years is one of the highest in Europe (2) and is likely to be accompanied by an increased burden of rheumatoid arthritis (RA) (3). Abatacept is approved as a first-line biologic after dis-ease-modifying anti-rheumatic drug failure in Italy (4). Lower abatacept retention rates have been reported in European countries with easier access to biologics (1). However, Italian patients were among the least likely to discontinue abatacept in the large, 2-year, non-interventional, international ACTION cohort study (NCT02109666) in which pre-scribing guidelines and reimbursement were uniform across participating countries (5).To provide a local perspective on the im-pact of patient characteristics on retention rate and clinical response to abatacept, we analysed the 12-month data in the Italian cohort of ACTION (n=441). Patients ≥18 years old with moderate-to-severe RA were enrolled prospectively at initiation of intra-venous abatacept or retrospectively within 3 months of the first abatacept dose accord-ing to local requirements (6). Baseline rheu-matoid factor (RF)/anti-citrullinated protein antibody (ACPA) serostatus was available for 371/441 patients: 183/371 (49%) were dou-ble RF/ACPA-positive; 112/371 (30%) were single RF- or ACPA-positive; and 76/371 (20%) were double RF/ACPA-negative. Baseline body mass index (BMI) was report-ed in 435/441 patients: 224/435 (51%) were underweight / normal; 130/435 (30%) were overweight; and 81/435 (19%) were obese. Baseline seropositivity had a significant impact on the crude abatacept retention rate at 12 months (log-rank test: p=0.043; Fig. 1a). Crude abatacept retention rates (95% confidence intervals [CIs]) at 12 months in the Italian cohort were higher in single RF- or ACPA-positive or double RF/ACPA-positive patients (85.1% [76.9, 90.6] and 80.2% [73.6, 85.4], respectively) than in double RF/ACPA-negative patients (70.3% [58.5, 79.4]). Over 12 months, abatacept discontinuation rates due to inefficacy were numerically lower with baseline seroposi-tivity versus seronegativity: 25/35, 14/20 and 18/23 patients in the double RF/AC-PA-positive, single RF- or ACPA-positive and double RF/ACPA-negative subgroups, respectively. RF/ACPA positivity on abata-cept initiation was associated with a trend towards improved good / moderate   EULAR response rates (95% CIs) based on Disease Activity Score in 28 joints (erythrocyte sedimentation rate, otherwise C-reactive protein) at 12 months: 83.7% (76.5, 90.8), 73.1% (63.2, 82.9) and 65.9% (52.4, 79.5) in the double RF/ACPA-positive, single RF- or ACPA-positive and double RF/ACPA-nega-tive subgroups, respectively (Fisher’s exact test: p=0.056).Crude abatacept retention rates (95% CIs) at 12 months were similar across BMI subgroups: 75.5% (69.2, 80.7), 82.1% (74.1, 87.8) and 79.4% (68.6, 86.9) in the underweight/normal, overweight and obese subgroups, respectively (log-rank test: p=0.629; Fig. 1b). Over 12 months, abatacept discontinuation rates due to in-efficacy were numerically higher in the obese versus the underweight / normal and overweight subgroups at 15/17, 37/53 and 18/25 patients, respectively, and were asso-ciated with a higher rate of co-morbidity. Discontinuation rates due to intolerance were lower in the obese versus the under-weight / normal and overweight subgroups: 2/17, 9/53 and 5/25 patients, respectively. There were no significant differences in good / moderate EULAR response rates (95% CIs) at 12 months across baseline BMI subgroups: 76.5% (68.8, 84.1), 75.9% (66.7, 85.1) and 73.3% (60.4, 86.3) in the underweight / normal, overweight and obese subgroups, respectively (Fisher’s exact test: p=0.854).Our findings for the Italian cohort of ACTION demonstrate improved abatacept retention and clinical response with RF/ACPA positivity and are consistent with 2-year results for the overall international population (5), and for a European RA registry analysis (7). Baseline BMI did not impact abatacept retention or clinical response, also consistent with the overall ACTION study and an international regis-try analysis (5, 8). These findings highlight the relevance of abatacept real-world data in different patient subpopulations to the management of RA in Italy.Fig. 1. Crude retention rate of abatacept by a) RF/ACPA serostatus and b) body mass index, in the Italian cohort of ACTION. ACPA: anti-citrullinated protein antibody; CI: confidence interval; pt: patient; RF: rheumatoid factor.936 Clinical and Experimental Rheumatology 2018Letters to the EditorsAcknowledgementsThe authors would like to thank Elisa Mazzini and Francesco De Solda for their role in reviewing the paper. The clinical research organisation involved in the AC-TION study in Italy was TFS Trial Form Support S.r.l. and statistical analysis sup-port was provided by Florence Mercier at Stat Process. Professional medical writing and editorial assistance was provided by Linda Brown at Caudex and was funded by Bristol-Myers Squibb.M. GALEAZZI1, MDR. ALTEN2, MD, PhDM. CHARTIER3, MScY. ELBEZ4, MScE. FUSARO5, MDM. LE BARS3*, PhDH.-M. LORENZ6, MD, PhDG. PAGANO MARIANO7, MDM. MURATORE8, MDH.G. NÜßLEIN9, MD G. PATANÈ10, MD, PhD1University of Siena, Italy; 2Schlosspark-Klinik University Medicine, Berlin, Germany; 3Bristol-Myers Squibb, Rueil-Malmaison, France; 4Excelya, Boulogne-Billancourt, France; 5A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy; 6University Hospital, Heidelberg, Germany; 7Unit of Rheumatology, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy; 8Unità Operativa di Reumatologia, Presidio Ospedaliero Vito Fazzi, San Cesario di Lecce, Italy; 9University of Erlangen-Nuremberg, Nuremberg, Germany; 10Bristol-Myers Squibb, Rome, Italy.*Affiliation at the time of the studyPlease address correspondence to: Giovanni Patanè, Bristol-Myers Squibb S.r.l., Piazzale dell’Industria, 40-46 00144 Rome, Italy.E-mail: giovanni.patane@bms.comCompeting interests: R. Alten has received research grants and consulting fees and is on a speaker bureau for Bristol-Myers Squibb. M. Chartier is an employee of Bristol-Myers Squibb. Y. Elbez is an employee of Excelya and has received consulting fees from Bristol-Myers Squibb. M. Le Bars and G. Patanè,are employees and shareholders of Bristol-Myers Squibb. H.-M. Lorenz is a consultant for AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, Sobi, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer and Actelion, and is on speaker bureaus for AbbVie, Bristol-Myers Squibb, Roche-Chugai, UCB, MSD, GSK, SOBI, Medac, Novartis, Janssen-Cilag, AstraZeneca, Pfizer and Actelion. H.G. Nüßlein is a consultant and is on speaker bureaus for Bristol-Myers Squibb, AbbVie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. The other co-authors have declared no competing interests.Received on March 16, 2017; accepted in revised form on September 11, 2017.© Copyright CliniCal and ExpErimEntal rhEumatology 2018.References  1. FINCKH A, NETO D, IANNONE F et al.: The impact of patient heterogeneity and socioeconomic fac-tors on abatacept retention in rheumatoid arthritis across nine European countries. RMD Open 2015; 1: e000040.  2. EUROPEAN COMMISSION ECONOMIC POLICY COMMITTEE: The 2012 Ageing Report: Underly-ing Assumptions and Projection Methodologies. European Economy 4/2011. European Commission Directorate-General for Economic and Financial Affairs; 2011. Available from: http://ec.europa.eu/economy_finance/publications/european_econo-my/2011/pdf/ee-2011-4_en.pdf. Accessed June 19, 2017.  3. CROSS M, SMITH E, HOY D et al.: The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73: 1316-22.   4. CAPORALI R, CONTI F, ALIVERNINI S et al.: Recommendations for the use of biology therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology. I. Efficacy. Clin Exp Rheumatol 2011; 29 (Suppl. 66): S7-14.  5. NÜßLEIN HG, ALTEN R, GALEAZZI M et al.: Efficacy and prognostic factors of treatment reten-tion with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study. Clin Exp Rheumatol 2016; 34: 489-99.  6. NÜßLEIN H, ALTEN R, GALEAZZI M et al.: Real-world effectiveness of abatacept for rheu-matoid arthritis treatment in European and Cana-dian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study. BMC Musculoskelet Disord 2014; 15: 14.   7. GOTTENBERG JE, COURVOISIER DS, HERNAN-DEZ MV et al.: Brief report: association of rheuma-toid factor and anti-citrullinated protein antibody positivity with better effectiveness of abatacept: results from the pan-European registry analysis. Arthritis Rheumatol 2016; 68: 1346-52.  8. IANNONE F, COURVOISIER DS, GOTTENBERG JE et al.: Body mass does not impact the clinical response to intravenous abatacept in patients with rheumatoid arthritis. 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Retention and clinical response to abatacept in patients with rheumatoid arthritis: an Italian perspective

https://usiena-air.unisi.it/bitstream/11365/1057974/2/Retention%20and%20clinical%20response%20to%20abatacept%20in%20patients%20with%20rheumatoid%20arthritis.pdf

Retention and clinical response to abatacept in patients with rheumatoid arthritis: an Italian perspective

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