Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: Results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

被引：12

作者：

Chanchlani, Neil ^{[1
]}

Lin, Simeng ^{[1
]}

Auth, Marcus K. ^{[2
]}

Lee, Chai Leng ^{[2
]}

Robbins, Helena ^{[3
]}

Looi, Shi ^{[3
]}

Murugesan, Senthil, V ^{[4
]}

Riley, Tom ^{[4
]}

Preston, Cathryn ^{[5
]}

Stephenson, Sophie ^{[5
]}

Cardozo, Wendy ^{[5
]}

Sonwalkar, Sunil A. ^{[6
]}

Allah-Ditta, Mohammed ^{[6
]}

Mansfield, Lynne ^{[6
]}

Durai, Dharmaraj ^{[7
]}

Baker, Mark ^{[7
]}

London, Ian ^{[8
]}

London, Emily ^{[8
]}

Gupta, Sanjay ^{[9
]}

Di Mambro, Alex ^{[10
]}

Murphy, Aisling ^{[10
]}

Gaynor, Edward ^{[11
]}

Jones, Kelsey D. J. ^{[11
]}

Claridge, Andrew ^{[12
]}

Sebastian, Shaji ^{[13
]}

Ramachandran, Sankaranarayanan ^{[13
]}

Selinger, Christian P. ^{[14
]}

Borg-Bartolo, Simon P. ^{[15
]}

Knight, Paul ^{[15
]}

Sprakes, Michael B. ^{[16
]}

Burton, Julie ^{[16
]}

Kane, Patricia ^{[16
]}

Lupton, Stephanie ^{[16
]}

Fletcher, Aimee ^{[16
]}

Gaya, Daniel R. ^{[17
]}

Colbert, Roghan ^{[17
]}

Seenan, John Paul ^{[18
]}

MacDonald, Jonathan ^{[18
]}

Lynch, Lucy ^{[18
]}

McLachlan, Iain ^{[18
]}

Shields, Stephanie ^{[18
]}

Hansen, Richard ^{[19
]}

Gervais, Lisa ^{[19
]}

Jere, Mwansa ^{[19
]}

Akhtar, Muhammad ^{[20
]}

Black, Karen ^{[20
]}

Henderson, Paul ^{[21
]}

Russell, Richard K. ^{[21
]}

Lees, Charlie W. ^{[22
]}

Derikx, Lauranne A. A. P. ^{[22
]}

机构：

[1] Royal Devon Univ Healthcare NHS Fdn Trust, Exeter, Devon, England

[2] Alder Hey Childrens NHS Fdn Trust, Liverpool, Merseyside, England

[3] Ashford & St Peters Hosp NHS Fdn Trust, Chertsey, England

[4] Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England

[5] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England

[6] Calderdale & Huddersfield Royal Infirm, Huddersfield, W Yorkshire, England

[7] Cardiff & Value Univ Hlth Board, Cardiff, Wales

[8] Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England

[9] Croydon Hlth Serv NHS Trust, Croydon, England

[10] Gloucestershire Hosp NHS Fdn Trust, Gloucester, England

[11] Great Ormond St Hosp Sick Children, London, England

[12] Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England

[13] Hull Univ Teaching Hosp NHS Trust, Kingston Upon Hull, N Humberside, England

[14] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[15] Manchester Univ NHS Fdn Trust, Manchester, Lancs, England

[16] Mid Yorkshire Hosp NHS Trust, Wakefield, England

[17] NHS Greater Glasgow & Clyde Glasgow Royal Infirm, Glasgow, Lanark, Scotland

[18] NHS Greater Glasgow & Clyde Queen Elizabeth Univ, Glasgow, Lanark, Scotland

[19] NHS Greater Glasgow & Clyde Royal Hosp Sick Child, Glasgow, Lanark, Scotland

[20] NHS Lanarkshire Univ Hosp Wishaw, Wishaw, England

[21] NHS Lothian Royal Hosp Sick Children, Edinburgh, Midlothian, Scotland

[22] NHS Lothian Western Gen Hosp, Edinburgh, Midlothian, Scotland

[23] North Bristol NHS Trust, Bristol, Avon, England

[24] Royal Berkshire NHS Fdn Trust, Reading, Berks, England

[25] Royal Cornwall Hosp NHS Trust, Turo, Cornwall, England

[26] Shrewsbury & Telford Hosp NHS Trust, Shrewsbury, Salop, England

[27] St Georges Univ Hosp NHS Fdn Trust, London, England

[28] St Helens & Knowsley Teaching Hosp NHS Trust, Rainhill, England

[29] Stockport NHS Fdn Trust, Stockport, Lancs, England

[30] Taunton & Somerset NHS Fdn Trust, Taunton, Somerset, England

[31] Torbay & South Devon NHS Fdn Trust, Torquay, England

[32] Univ Coll London Hosp NHS Fdn Trust, London, England

[33] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[34] Univ Hosp Bristol, Bristol, Avon, England

[35] Weston NHS Fdn Trust Bristol, Bristol, Avon, England

[36] Univ Hosp Bristol, Weston, England

[37] Weston NHS Fdn Trust Weston, Weston, England

[38] Univ Hosp Dorset NHS Fdn Trust, Poole, Dorset, England

来源：

ALIMENTARY PHARMACOLOGY & THERAPEUTICS | 2022年 / 56卷 / 08期

关键词：

CROHNS-DISEASE; ANTIBODIES; INFLIXIMAB; ADALIMUMAB; PHARMACOKINETICS; SWITCHERS; ALGORITHM; EFFICACY;

D O I：

10.1111/apt.17170

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). Aim: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to their second, irrespective of drug sequence Methods: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF drug, defined at any timepoint as an anti-TNF antibody concentration >= 9 AU/ml for infliximab and >= 6 AU/ml for adalimumab. Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. Conclusion: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second anti-TNF, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

引用

页码：1250 / 1263

页数：14

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