title: Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis.
abstract: OBJECTIVE
  Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients' ATI status.
  
  
  METHODS
  MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias.
  
  
  RESULTS
  Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95% confidence interval (CI): 2.0-4.9, P<0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P<0.0001). Data only from patients with ulcerative colitis (n=86) exhibited a non-significant RR of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n=243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P<0.0001). A funnel plot suggested the presence of publication bias.
  
  
  CONCLUSIONS
  The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.
authors.affiliation: Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kavinderjit S
authors.initials: KS
authors.lastname: Nanda
authors.forename: Adam S
authors.initials: AS
authors.lastname: Cheifetz
authors.forename: Alan C
authors.initials: AC
authors.lastname: Moss
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab; D060046:Maintenance Chemotherapy; D017211:Treatment Failure
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015415:Biomarkers; C048844:anti-IgG; D000069285:Infliximab