PMID- 29383030
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240327
IS  - 1756-283X (Print)
IS  - 1756-2848 (Electronic)
IS  - 1756-283X (Linking)
VI  - 11
DP  - 2018
TI  - Immunogenicity of biologics in inflammatory bowel disease.
PG  - 1756283X17750355
LID - 10.1177/1756283X17750355 [doi]
LID - 1756283X17750355
AB  - Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the 
      gastrointestinal tract. Treatment options include biologic therapies; however, a 
      proportion of patients lose response to biologics, partly due to the formation of 
      anti-drug antibodies (ADAbs). Concomitant immunosuppressive agents reduce the 
      development of ADAbs. This review article aims to assess the immunogenicity of 
      biologic therapies and their clinical implications. A comprehensive literature 
      search was conducted for articles published January 2009 to August 2015 reporting 
      immunogenicity to adalimumab (ADM), certolizumab pegol (CZP), golimumab, 
      infliximab (IFX), ustekinumab, and vedolizumab in inflammatory bowel disease 
      (IBD). Eligible articles were reviewed and quality assessed by independent 
      reviewers. Overall, 122 publications reporting 114 studies were assessed. ADAbs 
      were reported for all agents, but the percentage of patients developing ADAbs was 
      extremely variable, with the highest (65.3%) being for IFX administration to 
      patients with IBD. ADAb presence was frequently associated with a reduction in 
      primary efficacy and a loss of response, and, for IFX, an increase in adverse 
      events (AEs). Lower serum levels of ADM, CZP and IFX were seen in ADAbs-positive 
      rather than ADAbs-negative patients; pharmacokinetic data were unavailable for 
      other therapies. Little information was available regarding the timing of ADAb 
      development; studies reported their detection from as early as 10-14 days up to 
      months after treatment initiation. Biologic therapies carry an intrinsic risk of 
      immunogenicity, although reported rates of ADAbs vary considerably. The clinical 
      implications of immunogenicity are a concern for effective treatment; further 
      research, particularly into the more recently approved biologics, is required.
FAU - Vermeire, Severine
AU  - Vermeire S
AD  - Department of Gastroenterology, University Hospitals Leuven, Herestraat 49, 3000 
      Leuven, Belgium.
FAU - Gils, Ann
AU  - Gils A
AD  - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 
      Belgium.
FAU - Accossato, Paola
AU  - Accossato P
AD  - Pfizer Innovative Health, Pfizer S.r.l, Rome, Italy.
FAU - Lula, Sadiq
AU  - Lula S
AD  - Market Access Solutions, Envision Pharma Group Ltd, London, UK.
FAU - Marren, Amy
AU  - Marren A
AD  - Pfizer Innovative Health, Pfizer Inc, Collegeville, PA, USA.
LA  - eng
PT  - Journal Article
DEP - 20180121
PL  - England
TA  - Therap Adv Gastroenterol
JT  - Therapeutic advances in gastroenterology
JID - 101478893
PMC - PMC5784568
OTO - NOTNLM
OT  - Crohn's disease
OT  - anti-drug antibodies
OT  - biologic therapy
OT  - immunogenicity
OT  - ulcerative colitis
COIS- Conflict of interest statement: SV has received consulting fees from AbbVie, MSD, 
      Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, 
      Hospira, Celgene, Second Genome and Janssen; research grants from AbbVie, MSD and 
      Takeda; and speaker fees from AbbVie, MSD, Takeda, Ferring, Dr Falk Pharma, 
      Hospira and Tillot. AG has received speaker fees from AbbVie, MSD, Takeda, 
      Pfizer, Hospira and Janssen Biologicals; consulting fees from UCB; and research 
      grants from Pfizer Inc. SL is an employee of Engage Scientific, a Division of 
      Envision Pharma Group Ltd, which acted as a paid consultant to Pfizer in 
      connection with the conduct of the systematic literature review and 
      interpretation of data. PA and AM are employees and stockholders of Pfizer Inc.
EDAT- 2018/02/01 06:00
MHDA- 2018/02/01 06:01
PMCR- 2018/01/21
CRDT- 2018/02/01 06:00
PHST- 2017/07/05 00:00 [received]
PHST- 2017/11/21 00:00 [accepted]
PHST- 2018/02/01 06:00 [entrez]
PHST- 2018/02/01 06:00 [pubmed]
PHST- 2018/02/01 06:01 [medline]
PHST- 2018/01/21 00:00 [pmc-release]
AID - 10.1177_1756283X17750355 [pii]
AID - 10.1177/1756283X17750355 [doi]
PST - epublish
SO  - Therap Adv Gastroenterol. 2018 Jan 21;11:1756283X17750355. doi: 
      10.1177/1756283X17750355. eCollection 2018.