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 language | English |
|---|---|
| Pages (from-to) | 208-213 |
| Number of pages | 6 |
| Journal | Annals of the Rheumatic Diseases |
| Volume | 76 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2017 |
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 › peer-review
}
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 - Results from the BRAGGSS cohort
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
C2 - 27245864
AN - SCOPUS:85009723388
VL - 76
SP - 208
EP - 213
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 1
ER -