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. Raftery & 221 others C. 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

Research output: Contribution to journal › Article

12 Citations (Scopus)

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.

LanguageEnglish
Pages208-213
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number1
DOIs
StatusPublished - 1 Jan 2017

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Rheumatoid Arthritis
Antibodies
Pharmaceutical Preparations
Rheumatic Diseases
Certolizumab Pegol
Serum
Antibody Formation
Radioimmunoassay
Logistics
Therapeutics
Joints
Logistic Models
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

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

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

In: Annals of the Rheumatic Diseases, Vol. 76, No. 1, 01.01.2017, p. 208-213.

Research output: Contribution to journal › Article

Jani, M, Isaacs, JD, Morgan, AW, Wilson, AG, Plant, D, Hyrich, KL, Chinoy, H, Barton, A, Prouse, PJ, Moitra, RK, Shawe, DJ, Nisar, M, Fairburn, K, Nixon, J, Barnes, T, Hui, M, Coady, D, Wright, D, Morley, C, Raftery, G, Bracewell, C, Bridges, M, Armstrong, D, Chuck, AJ, Hailwood, S, Kumar, N, Ashok, D, Reece, R, O'Reilly, SC, Ding, T, Badcock, LJ, Deighton, CM, Raj, N, Regan, MR, Summers, GD, Williams, RA, Lambert, JR, Stevens, R, Wilkinson, C, Kelly, CA, Hamilton, J, Heycock, CR, Saravanan, V, Cope, A, Garrood, T, Ng, N, Kirkham, B, Green, M, Gough, A, Lawson, C, Das, D, Borbas, E, Wazir, T, Emery, P, Bingham, S, Morgan, A, Bird, HA, Conaghan, PG, Pease, CT, Wakefield, RJ, Buch, M, Bruce, I, Barton, A, Gorodkin, R, Ho, P, Hyrich, KL, Parker, B, Smith, W, Jenkins, E, Mukhtyar, C, Gaffney, K, Macgregor, AJ, Marshall, T, Merry, P, DeSilva, C, Birrell, FN, Crook, PR, Szebenyi, B, Bates, D, James, D, Gillott, T, Alvi, A, Grey, C, Browning, J, McHale, JF, Gaywood, IC, Jones, AC, Lanyon, P, Pande, I, Doherty, M, Gupta, A, Courtney, PA, Srikanth, A, Abhishek, A, Das, L, Pattrick, M, Snowden, HN, Bowden, AP, Smith, EE, Klimiuk, P, Speden, DJ, Naz, S, Ledingham, JM, Hull, RG, McCrae, F, Cooper, A, Young-Min, SA, Wong, E, Shaban, R, Woolf, AD, Davis, M, Hutchinson, D, Endean, A, Mewar, D, Tunn, EJ, Nelson, K, Kennedy, TD, Dubois, C, Pauling, J, Korendowych, E, Jenkinson, T, Sengupta, R, Bhalla, A, McHugh, N, Chinoy, H, O'Neill, T, Herrick, AL, Jones, AC, Cooper, RG, Dixon, WG, Harrison, B, Buckley, CD, Carruthers, DC, Elamanchi, R, Gordon, PC, Grindulis, KA, Khattak, F, Raza, K, Situnayake, K, Akil, M, Till, S, Dunkley, L, Tattersall, R, Kilding, R, Tait, T, Maxwell, J, Till, S, Kuet, KP, Plant, MJ, Clarke, F, Fordham, JN, Tuck, S, Pathare, SK, Paul, A, Marguerie, CP, Rigby, SP, Dunn, N, Abbas, I, Filer, C, Abernethy, VE, Clewes, AR, Dawson, JK, Kitas, G, Erb, N, Klocke, R, Whallett, AJ, Douglas, K, Pace, A, Sandhu, R, John, H, Shand, L, Lane, S, Isaacs, JD, Foster, H, Griffiths, B, Griffiths, I, Kay, L, Ng, WF, Platt, PN, Walker, DJ, Peterson, P, Lorenzi, A, Friswell, M, Thompson, B, Lee, M, Pratt, A, Hopkinson, ND, Dunne, CA, Quilty, B, Marks, J, Mukherjee, S, Mulherin, D, Chalam, SV, Price, T, Sheeran, T, Venkatachalam, S, Baskar, S, Al-Allaf, W, McKenna, F, Shah, P, Filer, A, Bowman, SJ, Jobanputra, P, Rankin, EC, Allen, M, Chaudhuri, K, Dubey, S, Price-Forbes, A, Ravindran, J, Samanta, A, Sheldon, P, Hassan, W, Francis, J, Kinder, A, Neame, R, Moorthy, A, Bukhari, M, Ottewell, L, Palkonyai, E, Hider, S, Hassell, A, Menon, A, Dowson, C, Kamath, S, Packham, J, Dutta, S, Price, S, Roddy, E, Paskins, Z, O'Reilly, DT, Rajagopal, V, Bhagat, S, Chattopadhyay, CB, Green, M, Quinn, D, Isdale, A, Brown, A, Saleem, B, Foo, B, Al Saffar, Z & Koduri, G 2017, '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', Annals of the Rheumatic Diseases, vol. 76, no. 1, pp. 208-213. https://doi.org/10.1136/annrheumdis-2015-208849
Jani M, Isaacs JD, Morgan AW, Wilson AG, Plant D, Hyrich KL et al. 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. Annals of the Rheumatic Diseases. 2017 Jan 1;76(1):208-213. https://doi.org/10.1136/annrheumdis-2015-208849
Jani, Meghna ; Isaacs, J. D. ; Morgan, Ann W. ; Wilson, Anthony G. ; Plant, Darren ; Hyrich, Kimme L. ; Chinoy, Hector ; Barton, Anne ; Prouse, P. J. ; Moitra, R. K. ; Shawe, D. J. ; Nisar, M. ; Fairburn, K. ; Nixon, J. ; Barnes, T. ; Hui, M. ; Coady, D. ; Wright, D. ; Morley, C. ; Raftery, G. ; Bracewell, C. ; Bridges, M. ; Armstrong, D. ; Chuck, A. J. ; Hailwood, S. ; Kumar, N. ; Ashok, D. ; Reece, R. ; O'Reilly, S. C. ; Ding, T. ; Badcock, L. J. ; Deighton, C. M. ; Raj, N. ; Regan, M. R. ; Summers, G. D. ; Williams, R. A. ; Lambert, J. R. ; Stevens, R. ; Wilkinson, C. ; Kelly, C. A. ; Hamilton, J. ; Heycock, C. R. ; Saravanan, V. ; Cope, A. ; Garrood, T. ; Ng, N. ; Kirkham, B. ; Green, M. ; Gough, A. ; Lawson, C. ; Das, D. ; Borbas, E. ; Wazir, T. ; Emery, P. ; Bingham, S. ; Morgan, A. ; Bird, H. A. ; Conaghan, P. G. ; Pease, C. T. ; Wakefield, R. J. ; Buch, M. ; Bruce, I. ; Barton, A. ; Gorodkin, R. ; Ho, P. ; Hyrich, K. L. ; Parker, B. ; Smith, W. ; Jenkins, E. ; Mukhtyar, C. ; Gaffney, K. ; Macgregor, A. J. ; Marshall, T. ; Merry, P. ; DeSilva, C. ; Birrell, F. N. ; Crook, P. R. ; Szebenyi, B. ; Bates, D. ; James, D. ; Gillott, T. ; Alvi, A. ; Grey, C. ; Browning, J. ; McHale, J. F. ; Gaywood, I. C. ; Jones, A. C. ; Lanyon, P. ; Pande, I. ; Doherty, M. ; Gupta, A. ; Courtney, P. A. ; Srikanth, A. ; Abhishek, A. ; Das, L. ; Pattrick, M. ; Snowden, H. N. ; Bowden, A. P. ; Smith, E. E. ; Klimiuk, P. ; Speden, D. J. ; Naz, S. ; Ledingham, J. M. ; Hull, R. G. ; McCrae, F. ; Cooper, A. ; Young-Min, S. A. ; Wong, E. ; Shaban, R. ; Woolf, A. D. ; Davis, M. ; Hutchinson, D. ; Endean, A. ; Mewar, D. ; Tunn, E. J. ; Nelson, K. ; Kennedy, T. D. ; Dubois, C. ; Pauling, J. ; Korendowych, E. ; Jenkinson, T. ; Sengupta, R. ; Bhalla, A. ; McHugh, N. ; Chinoy, H. ; O'Neill, T. ; Herrick, A. L. ; Jones, A. C. ; Cooper, R. G. ; Dixon, W. G. ; Harrison, B. ; Buckley, C. D. ; Carruthers, D. C. ; Elamanchi, R. ; Gordon, P. C. ; Grindulis, K. A. ; Khattak, F. ; Raza, K. ; Situnayake, K. ; Akil, M. ; Till, S. ; Dunkley, L. ; Tattersall, R. ; Kilding, R. ; Tait, T. ; Maxwell, J. ; Till, S. ; Kuet, K. P. ; Plant, M. J. ; Clarke, F. ; Fordham, J. N. ; Tuck, S. ; Pathare, S. K. ; Paul, A. ; Marguerie, C. P. ; Rigby, S. P. ; Dunn, N. ; Abbas, I. ; Filer, C. ; Abernethy, V. E. ; Clewes, A. R. ; Dawson, J. K. ; Kitas, G. ; Erb, N. ; Klocke, R. ; Whallett, A. J. ; Douglas, K. ; Pace, A. ; Sandhu, R. ; John, H. ; Shand, L. ; Lane, S. ; Isaacs, J. D. ; Foster, H. ; Griffiths, B. ; Griffiths, I. ; Kay, L. ; Ng, W. F. ; Platt, P. N. ; Walker, D. J. ; Peterson, P. ; Lorenzi, A. ; Friswell, M. ; Thompson, B. ; Lee, M. ; Pratt, A. ; Hopkinson, N. D. ; Dunne, C. A. ; Quilty, B. ; Marks, J. ; Mukherjee, S. ; Mulherin, D. ; Chalam, S. V. ; Price, T. ; Sheeran, T. ; Venkatachalam, S. ; Baskar, S. ; Al-Allaf, W. ; McKenna, F. ; Shah, P. ; Filer, A. ; Bowman, S. J. ; Jobanputra, P. ; Rankin, E. C. ; Allen, M. ; Chaudhuri, K. ; Dubey, S. ; Price-Forbes, A. ; Ravindran, J. ; Samanta, A. ; Sheldon, P. ; Hassan, W. ; Francis, J. ; Kinder, A. ; Neame, R. ; Moorthy, A. ; Bukhari, M. ; Ottewell, L. ; Palkonyai, E. ; Hider, S. ; Hassell, A. ; Menon, A. ; Dowson, C. ; Kamath, S. ; Packham, J. ; Dutta, S. ; Price, S. ; Roddy, E. ; Paskins, Z. ; O'Reilly, D. T. ; Rajagopal, V. ; Bhagat, S. ; Chattopadhyay, C. B. ; Green, M. ; Quinn, D. ; Isdale, A. ; Brown, A. ; Saleem, B. ; Foo, B. ; Al Saffar, Z. ; Koduri, G. / 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. In: Annals of the Rheumatic Diseases. 2017 ; Vol. 76, No. 1. pp. 208-213.
@article{a5508c4424f647b5973e00739596f866,
title = "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",
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.",
author = "Meghna Jani and Isaacs, {J. D.} and Morgan, {Ann W.} and Wilson, {Anthony G.} and Darren Plant and Hyrich, {Kimme L.} and Hector Chinoy and Anne Barton and Prouse, {P. J.} and Moitra, {R. K.} and Shawe, {D. J.} and M. Nisar and K. Fairburn and J. Nixon and T. Barnes and M. Hui and D. Coady and D. Wright and C. Morley and G. Raftery and C. Bracewell and M. Bridges and D. Armstrong and Chuck, {A. J.} and S. Hailwood and N. Kumar and D. Ashok and R. Reece and O'Reilly, {S. C.} and T. Ding and Badcock, {L. J.} and Deighton, {C. M.} and N. Raj and Regan, {M. R.} and Summers, {G. D.} and Williams, {R. A.} and Lambert, {J. R.} and R. Stevens and C. Wilkinson and Kelly, {C. A.} and J. Hamilton and Heycock, {C. R.} and V. Saravanan and A. Cope and T. Garrood and N. Ng and B. Kirkham and M. Green and A. Gough and C. Lawson and D. Das and E. Borbas and T. Wazir and P. Emery and S. Bingham and A. Morgan and Bird, {H. A.} and Conaghan, {P. G.} and Pease, {C. T.} and Wakefield, {R. J.} and M. Buch and I. Bruce and A. Barton and R. Gorodkin and P. Ho and Hyrich, {K. L.} and B. Parker and W. Smith and E. Jenkins and C. Mukhtyar and K. Gaffney and Macgregor, {A. J.} and T. Marshall and P. Merry and C. DeSilva and Birrell, {F. N.} and Crook, {P. R.} and B. Szebenyi and D. Bates and D. James and T. Gillott and A. Alvi and C. Grey and J. Browning and McHale, {J. F.} and Gaywood, {I. C.} and Jones, {A. C.} and P. Lanyon and I. Pande and M. Doherty and A. Gupta and Courtney, {P. A.} and A. Srikanth and A. Abhishek and L. Das and M. Pattrick and Snowden, {H. N.} and Bowden, {A. P.} and Smith, {E. E.} and P. Klimiuk and Speden, {D. J.} and S. Naz and Ledingham, {J. M.} and Hull, {R. G.} and F. McCrae and A. Cooper and Young-Min, {S. A.} and E. Wong and R. Shaban and Woolf, {A. D.} and M. Davis and D. Hutchinson and A. Endean and D. Mewar and Tunn, {E. J.} and K. Nelson and Kennedy, {T. D.} and C. Dubois and J. Pauling and E. Korendowych and T. Jenkinson and R. Sengupta and A. Bhalla and N. McHugh and H. Chinoy and T. O'Neill and Herrick, {A. L.} and Jones, {A. C.} and Cooper, {R. G.} and Dixon, {W. G.} and B. Harrison and Buckley, {C. D.} and Carruthers, {D. C.} and R. Elamanchi and Gordon, {P. C.} and Grindulis, {K. A.} and F. Khattak and K. Raza and K. Situnayake and M. Akil and S. Till and L. Dunkley and R. Tattersall and R. Kilding and T. Tait and J. Maxwell and S. Till and Kuet, {K. P.} and Plant, {M. J.} and F. Clarke and Fordham, {J. N.} and S. Tuck and Pathare, {S. K.} and A. Paul and Marguerie, {C. P.} and Rigby, {S. P.} and N. Dunn and I. Abbas and C. Filer and Abernethy, {V. E.} and Clewes, {A. R.} and Dawson, {J. K.} and G. Kitas and N. Erb and R. Klocke and Whallett, {A. J.} and K. Douglas and A. Pace and R. Sandhu and H. John and L. Shand and S. Lane and Isaacs, {J. D.} and H. Foster and B. Griffiths and I. Griffiths and L. Kay and Ng, {W. F.} and Platt, {P. N.} and Walker, {D. J.} and P. Peterson and A. Lorenzi and M. Friswell and B. Thompson and M. Lee and A. Pratt and Hopkinson, {N. D.} and Dunne, {C. A.} and B. Quilty and J. Marks and S. Mukherjee and D. Mulherin and Chalam, {S. V.} and T. Price and T. Sheeran and S. Venkatachalam and S. Baskar and W. Al-Allaf and F. McKenna and P. Shah and A. Filer and Bowman, {S. J.} and P. Jobanputra and Rankin, {E. C.} and M. Allen and K. Chaudhuri and S. Dubey and A. Price-Forbes and J. Ravindran and A. Samanta and P. Sheldon and W. Hassan and J. Francis and A. Kinder and R. Neame and A. Moorthy and M. Bukhari and L. Ottewell and E. Palkonyai and S. Hider and A. Hassell and A. Menon and C. Dowson and S. Kamath and J. Packham and S. Dutta and S. Price and E. Roddy and Z. Paskins and O'Reilly, {D. T.} and V. Rajagopal and S. Bhagat and Chattopadhyay, {C. B.} and M. Green and D. Quinn and A. Isdale and A. Brown and B. Saleem and B. Foo and {Al Saffar}, Z. and G. Koduri",
year = "2017",
month = "1",
day = "1",
doi = "10.1136/annrheumdis-2015-208849",
language = "English",
volume = "76",
pages = "208--213",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group Ltd",
number = "1",

}

TY - JOUR

T1 - High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis

T2 - Annals of the Rheumatic Diseases

AU - Jani, Meghna

AU - Isaacs, J. D.

AU - Morgan, Ann W.

AU - Wilson, Anthony G.

AU - Plant, Darren

AU - Hyrich, Kimme L.

AU - Chinoy, Hector

AU - Barton, Anne

AU - Prouse, P. J.

AU - Moitra, R. K.

AU - Shawe, D. J.

AU - Nisar, M.

AU - Fairburn, K.

AU - Nixon, J.

AU - Barnes, T.

AU - Hui, M.

AU - Coady, D.

AU - Wright, D.

AU - Morley, C.

AU - Raftery, G.

AU - Bracewell, C.

AU - Bridges, M.

AU - Armstrong, D.

AU - Chuck, A. J.

AU - Hailwood, S.

AU - Kumar, N.

AU - Ashok, D.

AU - Reece, R.

AU - O'Reilly, S. C.

AU - Ding, T.

AU - Badcock, L. J.

AU - Deighton, C. M.

AU - Raj, N.

AU - Regan, M. R.

AU - Summers, G. D.

AU - Williams, R. A.

AU - Lambert, J. R.

AU - Stevens, R.

AU - Wilkinson, C.

AU - Kelly, C. A.

AU - Hamilton, J.

AU - Heycock, C. R.

AU - Saravanan, V.

AU - Cope, A.

AU - Garrood, T.

AU - Ng, N.

AU - Kirkham, B.

AU - Green, M.

AU - Gough, A.

AU - Lawson, C.

AU - Das, D.

AU - Borbas, E.

AU - Wazir, T.

AU - Emery, P.

AU - Bingham, S.

AU - Morgan, A.

AU - Bird, H. A.

AU - Conaghan, P. G.

AU - Pease, C. T.

AU - Wakefield, R. J.

AU - Buch, M.

AU - Bruce, I.

AU - Barton, A.

AU - Gorodkin, R.

AU - Ho, P.

AU - Hyrich, K. L.

AU - Parker, B.

AU - Smith, W.

AU - Jenkins, E.

AU - Mukhtyar, C.

AU - Gaffney, K.

AU - Macgregor, A. J.

AU - Marshall, T.

AU - Merry, P.

AU - DeSilva, C.

AU - Birrell, F. N.

AU - Crook, P. R.

AU - Szebenyi, B.

AU - Bates, D.

AU - James, D.

AU - Gillott, T.

AU - Alvi, A.

AU - Grey, C.

AU - Browning, J.

AU - McHale, J. F.

AU - Gaywood, I. C.

AU - Jones, A. C.

AU - Lanyon, P.

AU - Pande, I.

AU - Doherty, M.

AU - Gupta, A.

AU - Courtney, P. A.

AU - Srikanth, A.

AU - Abhishek, A.

AU - Das, L.

AU - Pattrick, M.

AU - Snowden, H. N.

AU - Bowden, A. P.

AU - Smith, E. E.

AU - Klimiuk, P.

AU - Speden, D. J.

AU - Naz, S.

AU - Ledingham, J. M.

AU - Hull, R. G.

AU - McCrae, F.

AU - Cooper, A.

AU - Young-Min, S. A.

AU - Wong, E.

AU - Shaban, R.

AU - Woolf, A. D.

AU - Davis, M.

AU - Hutchinson, D.

AU - Endean, A.

AU - Mewar, D.

AU - Tunn, E. J.

AU - Nelson, K.

AU - Kennedy, T. D.

AU - Dubois, C.

AU - Pauling, J.

AU - Korendowych, E.

AU - Jenkinson, T.

AU - Sengupta, R.

AU - Bhalla, A.

AU - McHugh, N.

AU - Chinoy, H.

AU - O'Neill, T.

AU - Herrick, A. L.

AU - Jones, A. C.

AU - Cooper, R. G.

AU - Dixon, W. G.

AU - Harrison, B.

AU - Buckley, C. D.

AU - Carruthers, D. C.

AU - Elamanchi, R.

AU - Gordon, P. C.

AU - Grindulis, K. A.

AU - Khattak, F.

AU - Raza, K.

AU - Situnayake, K.

AU - Akil, M.

AU - Till, S.

AU - Dunkley, L.

AU - Tattersall, R.

AU - Kilding, R.

AU - Tait, T.

AU - Maxwell, J.

AU - Till, S.

AU - Kuet, K. P.

AU - Plant, M. J.

AU - Clarke, F.

AU - Fordham, J. N.

AU - Tuck, S.

AU - Pathare, S. K.

AU - Paul, A.

AU - Marguerie, C. P.

AU - Rigby, S. P.

AU - Dunn, N.

AU - Abbas, I.

AU - Filer, C.

AU - Abernethy, V. E.

AU - Clewes, A. R.

AU - Dawson, J. K.

AU - Kitas, G.

AU - Erb, N.

AU - Klocke, R.

AU - Whallett, A. J.

AU - Douglas, K.

AU - Pace, A.

AU - Sandhu, R.

AU - John, H.

AU - Shand, L.

AU - Lane, S.

AU - Isaacs, J. D.

AU - Foster, H.

AU - Griffiths, B.

AU - Griffiths, I.

AU - Kay, L.

AU - Ng, W. F.

AU - Platt, P. N.

AU - Walker, D. J.

AU - Peterson, P.

AU - Lorenzi, A.

AU - Friswell, M.

AU - Thompson, B.

AU - Lee, M.

AU - Pratt, A.

AU - Hopkinson, N. D.

AU - Dunne, C. A.

AU - Quilty, B.

AU - Marks, J.

AU - Mukherjee, S.

AU - Mulherin, D.

AU - Chalam, S. V.

AU - Price, T.

AU - Sheeran, T.

AU - Venkatachalam, S.

AU - Baskar, S.

AU - Al-Allaf, W.

AU - McKenna, F.

AU - Shah, P.

AU - Filer, A.

AU - Bowman, S. J.

AU - Jobanputra, P.

AU - Rankin, E. C.

AU - Allen, M.

AU - Chaudhuri, K.

AU - Dubey, S.

AU - Price-Forbes, A.

AU - Ravindran, J.

AU - Samanta, A.

AU - Sheldon, P.

AU - Hassan, W.

AU - Francis, J.

AU - Kinder, A.

AU - Neame, R.

AU - Moorthy, A.

AU - Bukhari, M.

AU - Ottewell, L.

AU - Palkonyai, E.

AU - Hider, S.

AU - Hassell, A.

AU - Menon, A.

AU - Dowson, C.

AU - Kamath, S.

AU - Packham, J.

AU - Dutta, S.

AU - Price, S.

AU - Roddy, E.

AU - Paskins, Z.

AU - O'Reilly, D. T.

AU - Rajagopal, V.

AU - Bhagat, S.

AU - Chattopadhyay, C. B.

AU - Green, M.

AU - Quinn, D.

AU - Isdale, A.

AU - Brown, A.

AU - Saleem, B.

AU - Foo, B.

AU - Al Saffar, Z.

AU - Koduri, G.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85009723388&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2015-208849

DO - 10.1136/annrheumdis-2015-208849

M3 - Article

VL - 76

SP - 208

EP - 213

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 1

ER -

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