High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: Results from the BRAGGSS cohort

Meghna Jani, J. D. Isaacs, Ann W. Morgan, Anthony G. Wilson, Darren Plant, Kimme L. Hyrich, Hector Chinoy, Anne Barton, P. J. Prouse, R. K. Moitra, D. J. Shawe, M. Nisar, K. Fairburn, J. Nixon, T. Barnes, M. Hui, D. Coady, D. Wright, C. Morley, G. RafteryC. Bracewell, M. Bridges, D. Armstrong, A. J. Chuck, S. Hailwood, N. Kumar, D. Ashok, R. Reece, S. C. O'Reilly, T. Ding, L. J. Badcock, C. M. Deighton, N. Raj, M. R. Regan, G. D. Summers, R. A. Williams, J. R. Lambert, R. Stevens, C. Wilkinson, C. A. Kelly, J. Hamilton, C. R. Heycock, V. Saravanan, A. Cope, T. Garrood, N. Ng, B. Kirkham, M. Green, A. Gough, C. Lawson, D. Das, E. Borbas, T. Wazir, P. Emery, S. Bingham, A. Morgan, H. A. Bird, P. G. Conaghan, C. T. Pease, R. J. Wakefield, M. Buch, I. Bruce, A. Barton, R. Gorodkin, P. Ho, K. L. Hyrich, B. Parker, W. Smith, E. Jenkins, C. Mukhtyar, K. Gaffney, A. J. Macgregor, T. Marshall, P. Merry, C. DeSilva, F. N. Birrell, P. R. Crook, B. Szebenyi, D. Bates, D. James, T. Gillott, A. Alvi, C. Grey, J. Browning, J. F. McHale, I. C. Gaywood, A. C. Jones, P. Lanyon, I. Pande, M. Doherty, A. Gupta, P. A. Courtney, A. Srikanth, A. Abhishek, L. Das, M. Pattrick, H. N. Snowden, A. P. Bowden, E. E. Smith, P. Klimiuk, D. J. Speden, S. Naz, J. M. Ledingham, R. G. Hull, F. McCrae, A. Cooper, S. A. Young-Min, E. Wong, R. Shaban, A. D. Woolf, M. Davis, D. Hutchinson, A. Endean, D. Mewar, E. J. Tunn, K. Nelson, T. D. Kennedy, C. Dubois, J. Pauling, E. Korendowych, T. Jenkinson, R. Sengupta, A. Bhalla, N. McHugh, H. Chinoy, T. O'Neill, A. L. Herrick, A. C. Jones, R. G. Cooper, W. G. Dixon, B. Harrison, C. D. Buckley, D. C. Carruthers, R. Elamanchi, P. C. Gordon, K. A. Grindulis, F. Khattak, K. Raza, K. Situnayake, M. Akil, S. Till, L. Dunkley, R. Tattersall, R. Kilding, T. Tait, J. Maxwell, S. Till, K. P. Kuet, M. J. Plant, F. Clarke, J. N. Fordham, S. Tuck, S. K. Pathare, A. Paul, C. P. Marguerie, S. P. Rigby, N. Dunn, I. Abbas, C. Filer, V. E. Abernethy, A. R. Clewes, J. K. Dawson, G. Kitas, N. Erb, R. Klocke, A. J. Whallett, K. Douglas, A. Pace, R. Sandhu, H. John, L. Shand, S. Lane, J. D. Isaacs, H. Foster, B. Griffiths, I. Griffiths, L. Kay, W. F. Ng, P. N. Platt, D. J. Walker, P. Peterson, A. Lorenzi, M. Friswell, B. Thompson, M. Lee, A. Pratt, N. D. Hopkinson, C. A. Dunne, B. Quilty, J. Marks, S. Mukherjee, D. Mulherin, S. V. Chalam, T. Price, T. Sheeran, S. Venkatachalam, S. Baskar, W. Al-Allaf, F. McKenna, P. Shah, A. Filer, S. J. Bowman, P. Jobanputra, E. C. Rankin, M. Allen, K. Chaudhuri, S. Dubey, A. Price-Forbes, J. Ravindran, A. Samanta, P. Sheldon, W. Hassan, J. Francis, A. Kinder, R. Neame, A. Moorthy, M. Bukhari, L. Ottewell, E. Palkonyai, S. Hider, A. Hassell, A. Menon, C. Dowson, S. Kamath, J. Packham, S. Dutta, S. Price, E. Roddy, Z. Paskins, D. T. O'Reilly, V. Rajagopal, S. Bhagat, C. B. Chattopadhyay, M. Green, D. Quinn, A. Isdale, A. Brown, B. Saleem, B. Foo, Z. Al Saffar, G. Koduri

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Abstract

Objectives: To evaluate (i) the association between random certolizumab drug levels, antidrug antibodies (ADAbs) and treatment response in patients with rheumatoid arthritis (RA); (ii) longitudinal factors associated with ADAbs and certolizumab drug levels. Methods: This prospective cohort included 115 patients with RA treated with certolizumab. Serum samples were collected at 3, 6 and 12 months following treatment initiation. Drug levels and ADAbs were measured using ELISA and radioimmunoassay, respectively, at 3, 6 and 12 months. Disease Activity Score in 28 joints (DAS28) were measured at each visit and 12 months European League Against Rheumatism (EULAR) response was calculated. Patient self-reported adherence was collected longitudinally. Ordinal logistic regression and generalised estimating equation were used to test the association: (i) between drug levels, from serum sampled and treatment response; (ii) between ADAbs and drug levels; (iii) patient-centred factors and drug levels. Results: ADAbs were detected in 37% (42/112 patients by 12 months). The presence of ADAbs were significantly associated with lower drug levels over 12 months (β=-0.037, 95% CI -0.055 to 0.018, p<0.0001) but not independently with 12 months EULAR response (β=0.0013 (95% CI -0.0032 to 0.00061), p=0.18). Drug level was associated with 12 months EULAR response (β=0.032 (95% CI 0.0011 to 0.063), p=0.042). In the multivariate model, ADAb level and adherence were significantly associated with drug concentrations. Conclusions: This is the first study to demonstrate that higher certolizumab drug levels are associated with better 12 months EULAR response. ADAbs in certolizumab-treated patients with RA were detected at higher levels than previous studies and help determine the aetiology of a low drug level.

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

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ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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