Original Article
pANCA Positivity Predicts Lower Clinical Response to Infliximab Therapy among Patients with IBD
Abstract
Objectives: Several studies have been performed evaluating the role of perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) to predict early clinical response among patients with inflammatory bowel disease (IBD) who are undergoing infliximab therapy. The results of these studies are variable, however, and the effect of pANCA+ as a predictor of clinical response to infliximab remains largely undefined. The goal of this meta-analysis was to evaluate the role of pANCA in predicting poor responders to infliximab.Methods: A comprehensive search of the PubMed/MEDLINE, Scopus, Cumulative Index of Nursing and Allied Health Literature, Google Scholar, and Cochrane databases was performed in June 2014. All of the studies that evaluated pANCA levels in patients with IBD who were undergoing antitumor necrosis factor-α (anti-TNF-α) therapy and their clinical responses were included. A meta-analysis was performed using the Mantel-Haenszel model with odds ratios (ORs) to assess for clinical remission.
Results: In the pooled analysis (N = 415), patients who were pANCA negative had nearly a twofold higher response to anti-TNF-α therapy compared with patients who were pANCA+ (odds ratio 1.87; 95% confidence interval 1.02–3.41). Serologic testing for pANCA+ predicting nonresponse to infliximab therapy showed a sensitivity of 25.2%, a specificity of 85.5%, a positive predictive value of 41.1%, and a negative predictive value of 74.0%.
Conclusions: Being more proactive (ie, early dose escalation or accelerated loading regimen) in patients who are pANCA+ may be necessary to improve clinical response.
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References
1. Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997;337:1029-1035.
2. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398-1405.
3. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002;359:1541-1549.
4. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476.
5. Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005;128:1805-1811.
6. Lacruz-Guzman D1, Torres-Moreno D, PedreroF, et al. Influence of polymorphisms and TNF and IL1 serum concentration on the infliximab response in Crohn’s disease and ulcerative colitis. Eur J Clin Pharmacol 2013;69:431-438.
7. Niess JH, Klaus J, Stephani J, et al. NOD2 polymorphism predicts response to treatment in Crohn’s disease–first steps to a personalized therapy. Dig Dis Sci 2012;57:879-886.
8. Lopez-Hernandez R, Valdes M, Campillo JA, et al. Genetic polymorphisms of tumour necrosis factor alpha (TNF-) promoter gene and response to TNF- inhibitors in Spanish patients with inflammatory bowel disease. Int J Immunogenet 2014;41:63-68.
9. Ruemmele FM, Targan SR, Levy G, et al. Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterology 1998;115:822-829.
10. Quinton JF, Sendid B, Reumaux D, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1998;42:788-791.
11. Hoffenberg EJ, Fidanza S, Sauaia A. Serologic testing for inflammatory bowel disease. J Pediatr 1999;134:447-452.
12. Duerr RH, Targan SR, Landers CJ, et al. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology 1991;100:1590-1596.
13. Dubinsky M. Can serologic markers help determine prognosis and guide therapy? Dig Dis. 2010;28:424-428.
14. Cambridge G, Rampton DS, Stevens TR, et al. Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1992;33:668-674.
15. Thomas BH, Ciliska D, Dobbins M, et al. A process for systematically reviewing the literature: providing the research evidence for public health nursing interventions. Worldviews Evid Based Nurs 2004;1:176-184.
16. Armijo-Olivo S, Stiles CR, Hagen NA, et al. Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract 2012;18:12-18.
17. Esters N, Vermeire S, Joossens S, et al. Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn’s disease. Am J Gastroenterol 2002;97:1458-1462.
18. Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis 2007;13:123-128.
19. Taylor KD, Plevy SE, Yang H, et al. ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn’s disease. Gastroenterology 2001;120:1347-1355.
20. Kevans D, Murthy S, Iacono A, et al. Accelerated clearance of serum infliximab during induction therapy for acute ulcerative colitis is associated with treatment failure. Gastroenterology 2012;142:S384-S385.
21. Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut 2014;63:1721-1727.
22. Pallagi-Kunstar E, Farkas K, Szepes Z, et al. Utility of serum TNF-, infliximab trough level, and antibody titers in inflammatory bowel disease. World J Gastroenterol 2014;20:5031-5035.
