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Abstract
Background Certolizumab pegol (CZP) has been shown to be efficacious and have an acceptable safety profile as a monotherapy (FAST4WARD/NCT00548834) or in combination with methotrexate (014/NCT00544154) for the treatment of rheumatoid arthritis (RA).1,2
Objectives To evaluate the long-term safety and efficacy of CZP monotherapy, or in combination with other DMARDs, over 5 years.
Methods The open-label extension (OLE) study (NCT00160693) enrolled patients (pts) who withdrew/completed the 24Wk FAST4WARD/014 studies. Pts received CZP 400mg Q4W for the duration of the study. The OLE objectives were to monitor safety and evaluate efficacy. Pts were permitted to take DMARDs in the OLE. Pt retention and efficacy (observed only) are reported up to Wk280 (5.4 years; last time point all sites open) and safety up to Wk364 (7 years; final data cut-point) in the OLE. Safety population included all OLE pts who received CZP (N=402; n=276 combination therapy, n=126 monotherapy), including PBO/CZP pts who completed/withdrew from either feeder study and entered OLE. Sub-populations analyzed for efficacy were (1) CZP feeder study completers who had received another DMARD at any point during either feeder/OLE studies (n=123; CZP combination completers) and (2) FAST4WARD CZP completers who entered OLE and did not receive any other DMARD at any point during either feeder/OLE studies (n=48; CZP monotherapy completers).
Results The pattern and frequency of adverse events (AEs), including injection site reaction (Event Rate/100-pt years: monotherapy 1.4, combination therapy 0.9), and serious AEs were consistent with those reported previously with CZP (Table). Serious infection and malignancy rates were low (Table). 11 deaths were reported: 7 cardiovascular events, 2 infectious, 1 injury and 1 malignancy. Retention at Wk280 was similar between CZP monotherapy (24/48, 50%) and combination therapy (67/123, 55%) completers. Mean(SD) DAS28-3(CRP) and change from feeder study baseline (CFB) were 3.9(1.2) and -1.9(1.4) in the monotherapy and 4.1(1.2) and -1.8(1.2) in the combination completers at OLE entry, and 2.9(1.1) and -3.1(1.6) in the monotherapy and 2.9(1.0) and -3.0(1.3) in the combination completers at Wk280. Mean(SD) HAQ and CFB were 0.9(0.8) and -0.6(0.7) in the monotherapy and 1.1(0.7) and -0.3(0.5) in the combination completers at OLE entry, and 0.8(0.9) and -0.7(0.8) in the monotherapy and 0.8(0.6) and -0.5(0.5) in the combination completers at Wk280.
Conclusions CZP monotherapy was confirmed to have a favourable risk-benefit profile within this study. Similar long-term efficacy was observed between pts who received CZP monotherapy and pts who received CZP in combination with other DMARDs; retention rates were also similar between these two groups.
References
Fleischmann R. Ann Rheum Dis 2009;68:805-811;
Choy E. Rheumatology 2012;51(7):1226-1234
Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.
Disclosure of Interest R. Fleischmann Grant/research support from: Genetech, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS, R. van Vollenhoven Grant/research support from: Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB Pharma, J. Vencovsky Consultant for: UCB Pharma, Roche, Abbott, Pfizer, MSD, Speakers bureau: UCB Pharma, Pfizer, Roche, MSD, R. Alten Consultant for: UCB Pharma, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, M. de Longueville Employee of: UCB Pharma, B. VanLunen Employee of: UCB Pharma, E. Choy Grant/research support from: Abbott, Allergan, AstraZeneca, Boehringer Ingelheim, Chelsea Therapeutics, Chugai, Daiichi Sankyo, Eli Lilly, Ferring Pharmaceutical, GSK, Jazz Pharmaceuticals, MedImmune, Merrimack Pharmaceutical, MSD, Novartis, Pfizer, Pierre Fabre Medicament, Roche, Schering-Plough, Synovate, UCB Pharma, Consultant for: Abbott, Allergan, AstraZeneca, Boehringer Ingelheim, Chelsea Therapeutics, Chugai, Daiichi Sankyo, Eli Lilly, Ferring Pharmaceutical, GSK, Jazz Pharmaceuticals, MedImmune, Merrimack Pharmaceutical, MSD, Novartis, Pfizer, Pierre Fabre Medicament, Roche, Schering-Plough, Synovate, UCB Pharma