دورية أكاديمية
HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn’s disease
| العنوان: | HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn’s disease |
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| المؤلفون: | Sazonovs, A, Kennedy, NA, Moutsianas, L, Heap, GA, Rice, DL, Reppell, M, Bewshea, CM, Chanchlani, N, Walker, GJ, Perry, MH, McDonald, TJ, Lees, CW, Cummings, JRF, Parkes, M, Mansfield, JC, Irving, PM, Barrett, JC, McGovern, D, Goodhand, JR, Anderson, CA, Ahmad, T, Patel, V, Mazhar, Z, Saich, R, Colleypriest, B, Tham, TC, Iqbal, TH, Kaushik, V, Murugesan, S, Singh, S, Weaver, S, Preston, C, Butt, A, Smith, M, Basude, D, Beale, A, Langlands, S, Direkze, N, Torrente, F, De La Revella Negro, J, Ewen MacDonald, C, Evans, SM, Gunasekera, AVJ, Thakur, A, Elphick, D, Shenoy, A, Nwokolo, CU, Dhar, A, Cole, AT, Agrawal, A, Bridger, S, Doherty, J, Cooper, SC, De Silva, S, Mowat, C, Mayhead, P, Lees, C, Jones, G, Hart, JW, Gaya, DR, Russell, RK, Gervais, L, Dunckley, P, Mahmood, T, Banim, PJR, Sonwalkar, S, Ghosh, D, Phillips, RH, Azaz, A, Sebastian, S, Shenderey, R, Armstrong, L, Bell, C, Hariraj, R, Matthews, H, Jafferbhoy, H, Selinger, CP, Zamvar, V, De Caestecker, JS, Willmott, A, Miller, R, Sathish Babu, P, Tzivinikos, C, Bloom, SL, Chung-Faye, G, Croft, NM, Fell, JME, Harbord, M, Hart, A, Hope, B, Lindsay, JO, Mawdsley, JE, McNair, A, Monahan, KJ, Murray, CD, Orchard, T, Paul, T, Pollok, R, Shah, N, Bouri, S, Johnson, MW, Modi, A, Dawa Kabiru, K, Baburajan, BK, Bhaduri, B, Adebayo Fagbemi, A, Levison, S, Limdi, JK, Watts, G, Foley, S, Ramadas, A, MacFaul, G, Mansfield, J, Grellier, L, Morris, M-A, Tremelling, M, Hawkey, C, Kirkham, S, Charlton, CPJ, Rodrigues, A, Simmons, A, Lewis, SJ, Snook, J, Tighe, M, Goggin, PM, De Silva, AN, Lal, S, Smith, MS, Panter, S, Cummings, F, Dharmisari, S, Carter, M, Watts, D, Mahmood, Z, McLain, B, Sen, S, Pigott, AJ, Hobday, D, Wesley, E, Johnston, R, Edwards, C, Beckly, J, Vani, D, Ramakrishnan, S, Chaudhary, R, Trudgill, NJ, Cooney, R, Bell, A, Prasad, N, Gordon, JN, Brookes, MJ, Li, A, Gore, S |
| المصدر: | 199 ; 189 |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2019 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Gastroenterology & Hepatology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, 1109 Neurosciences |
| الوصف: | Background & Aims Anti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. Methods We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn’s disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. Results The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60–2.25; P = 5.88 × 10–13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35–2.98; P = 6.60 × 10–4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32–2.70) or infliximab (HR, 1.92; 95% CI, 1.57–2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37–2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57–2.58). Conclusions In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0016-5085 |
| العلاقة: | Gastroenterology; http://hdl.handle.net/10044/1/75682Test |
| DOI: | 10.1053/j.gastro.2019.09.041 |
| الإتاحة: | https://doi.org/10.1053/j.gastro.2019.09.041Test http://hdl.handle.net/10044/1/75682Test |
| حقوق: | © 2020 by the AGA Institute. Published by Elsevier Inc. This is an openaccess article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). |
| رقم الانضمام: | edsbas.BE34FDC2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00165085 |
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| DOI: | 10.1053/j.gastro.2019.09.041 |