Mark C Genovese1,2, César Pacheco-Tena3,4, Arturo Covarrubias3,4, Gustavo Leon3,4, Eduardo Mysler3,4, Mauro Keiserman3,4, Robert M Valente3,4, Peter Nash3,4, J Abraham Simon-Campos3,4, Jane Box3,4, Clarence W Legerton3,4, Evgeny Nasonov3,4, Patrick Durez3,4, Ayanbola Elegbe3,4, Robert Wong3,4, Xiaohui Li3,4, Subhashis Banerjee3,4, Rieke Alten3,4. 1. From Stanford University, Palo Alto, California; Arthritis Center of Nebraska, Lincoln, Nebraska; Box Arthritis and Rheumatology of the Carolinas, Charlotte, North Carolina; Low Country Rheumatology, Charleston, South Carolina; Bristol-Myers Squibb, Princeton, New Jersey, USA; Universidad Autónoma de Chihuahua, Chihuahua; Unidad Reumatológica Las Américas S.C.P., Mérida; Köhler & Milstein Research, Mérida, Mexico; Instituto De Ginecología Y Reproducción, Lima, Peru; Organización Médica de Investigación, Buenos Aires, Argentina; Pontifical Catholic University, Porto Alegre, Brazil; University of Queensland, Brisbane, Australia; Russian Academy of Medical Sciences, Moscow, Russia; Cliniques Universitaires Saint-Luc; Université Catholique de Louvain, Brussels, Belgium; Schlosspark-Klinik University Medicine, Berlin, Germany. genovese@stanford.edu. 2. M.C. Genovese, MD, Stanford University; C. Pacheco-Tena, MD, PhD, Universidad Autónoma de Chihuahua; A. Covarrubias, MD, Unidad Reumatológica Las Américas S.C.P.; G. Leon, MD, Instituto De Ginecología Y Reproducción; E. Mysler, MD, Organización Médica de Investigación; M. Keiserman, MD, Pontifical Catholic University; R.M. Valente, MD, Arthritis Center of Nebraska; P. Nash, MBBS (Hons), FRACP, University of Queensland; J.A. Simon-Campos, PhD, Köhler & Milstein Research; J. Box, MD, Box Arthritis and Rheumatology of the Carolinas; C.W. Legerton III, MD, Low Country Rheumatology; E. Nasonov, PhD, Russian Academy of Medical Sciences; P. Durez, MD, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; A. Elegbe, PhD, Bristol-Myers Squibb; R. Wong, MD, Bristol-Myers Squibb; X. Li, PhD, Bristol-Myers Squibb; S. Banerjee, MD, Bristol-Myers Squibb; R. Alten, MD, PhD, Schlosspark-Klinik University Medicine. genovese@stanford.edu. 3. From Stanford University, Palo Alto, California; Arthritis Center of Nebraska, Lincoln, Nebraska; Box Arthritis and Rheumatology of the Carolinas, Charlotte, North Carolina; Low Country Rheumatology, Charleston, South Carolina; Bristol-Myers Squibb, Princeton, New Jersey, USA; Universidad Autónoma de Chihuahua, Chihuahua; Unidad Reumatológica Las Américas S.C.P., Mérida; Köhler & Milstein Research, Mérida, Mexico; Instituto De Ginecología Y Reproducción, Lima, Peru; Organización Médica de Investigación, Buenos Aires, Argentina; Pontifical Catholic University, Porto Alegre, Brazil; University of Queensland, Brisbane, Australia; Russian Academy of Medical Sciences, Moscow, Russia; Cliniques Universitaires Saint-Luc; Université Catholique de Louvain, Brussels, Belgium; Schlosspark-Klinik University Medicine, Berlin, Germany. 4. M.C. Genovese, MD, Stanford University; C. Pacheco-Tena, MD, PhD, Universidad Autónoma de Chihuahua; A. Covarrubias, MD, Unidad Reumatológica Las Américas S.C.P.; G. Leon, MD, Instituto De Ginecología Y Reproducción; E. Mysler, MD, Organización Médica de Investigación; M. Keiserman, MD, Pontifical Catholic University; R.M. Valente, MD, Arthritis Center of Nebraska; P. Nash, MBBS (Hons), FRACP, University of Queensland; J.A. Simon-Campos, PhD, Köhler & Milstein Research; J. Box, MD, Box Arthritis and Rheumatology of the Carolinas; C.W. Legerton III, MD, Low Country Rheumatology; E. Nasonov, PhD, Russian Academy of Medical Sciences; P. Durez, MD, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain; A. Elegbe, PhD, Bristol-Myers Squibb; R. Wong, MD, Bristol-Myers Squibb; X. Li, PhD, Bristol-Myers Squibb; S. Banerjee, MD, Bristol-Myers Squibb; R. Alten, MD, PhD, Schlosspark-Klinik University Medicine.
Abstract
OBJECTIVE: To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). METHODS: The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. RESULTS: Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. CONCLUSION: These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.
RCT Entities:
OBJECTIVE: To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). METHODS: The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. RESULTS: Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. CONCLUSION: These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.
Authors: Maurizio Benucci; Valentina Grossi; Mariangela Manfredi; Arianna Damiani; Maria Infantino; Paolo Moscato; Luigi Cinquanta; Elisa Gremese; Barbara Tolusso; Luca Petricca; Anna Laura Fedele; Stefano Alivernini; Fabiola Atzeni; Giovanni Minisola; Roberto Verna Journal: Ann Lab Med Date: 2020-03 Impact factor: 3.464