Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease
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To review the frequency with which anti-TNF-α loses its effect and dose “intensification” is required for Crohn’s disease (CD) treatment.
Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.
Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29–38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22–39) for adalimumab, and 41% (95% CI 30–53) for certolizumabpegol. Overall, the mean percentage of patients’ LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28–41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28–50), 36% (95% CI 30–43) for adalimumab, and 2% (95% CI 2–3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001).
Overall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders.
KeywordsLoss of response Anti-TNFα Dose intensification Crohn’s disease
- 8.Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(96–109):e1.Google Scholar
- 11.Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat. 1950:607–611.Google Scholar
- 18.Schwarzer G. Meta: An R package for meta-analysis. SpherWave: an R package for analyzing scattered spherical data by Spherical Wavelets 2007:40.Google Scholar
- 28.Gonzaga JE, Issa M, Skaros S, et al. W1255 Durability of infliximab in Crohn’s disease patients treated with maintenance infusions beyond one year. Gastroenterology. 2008;A-134:A-665–6.Google Scholar
- 40.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;63:1721–7.PubMedPubMedCentralCrossRefGoogle Scholar
- 47.Panaccione R, Sandborn WJ, D’Haens G, et al. 920 Adalimumab maintains long-term remission in moderately to severely active Crohn’s disease after infliximab failure: 1-year follow-up of gain trial. Gastroenterology. 2008;134:A-133–4.Google Scholar
- 48.Bortlik M, Duricova D, Komarek V, et al. W1225 Adalimumab in a clinical practice—experience with human anti TNF-α therapy in tertiary clinical center. Gastroenterology. 2009;136:A-682.Google Scholar
- 51.Chaparro M, Panes J, García V, et al. W1275 Long-Term Durability of Response to Adalimumab Treatment in Crohn’s Disease. Gastroenterology. 2010;138:S-689.Google Scholar
- 52.Russo E, O’Donnell S, Dearden J, et al. W1312 Long-term efficacy of the second biologic in the management of Crohn’s disease. A retrospective survey on an English-Irish cohort. Gastroenterology. 2010;138:S-697.Google Scholar
- 60.D’Haens G, Mitchev K, Sandborn WJ. T1126 Response and remission at 18 months of certolizumab pegol in patients with active Crohn’s disease is not influenced by rapidity and magnitude of induction: an analysis of PRECISE 2 and 3. Gastroenterology. 2008;134:489.Google Scholar
- 61.Sandborn WJ, Vermeire S, D’Haens GR, et al. 143 Welcome: a randomized, double-blind, controlled trial comparing certolizumab pegol 400 Mg every 2 weeks with every 4 weeks for maintenance of response and remission in patients with moderate to severe Crohn’s disease with secondary failure to infliximab. Gastroenterology. 2009;136:A-27.Google Scholar
- 63.Sandborn WJ, Abreu MT, D’Haens G, et al. Certolizumab pegol in patients with moderate to severe Crohn’s disease and secondary failure to infliximab. Clin Gastroenterol Hepatol. 2010;8(688–695):e2.Google Scholar
- 64.Sandborn WJ, Schreiber S, Hanauer SB, et al. Reinduction with certolizumab pegol in patients with relapsed Crohn’s disease: results from the PRECiSE 4 study. Clin Gastroenterol Hepatol. 2010;8(696–702):e1.Google Scholar
- 74.Sheridan JA KD, Slattery E. Adalimumab in Crohn’s disease. Gut 2008;Suppl 2:A2564.Google Scholar
- 80.Loftus Jr E, Pan X, Zurawski P. Dosage pattern of adalimumab in real-world clinical practice and predictors of dosage increase in patients with Crohn’s disease in the United States. Gastroenterology 2009;5.Google Scholar
- 88.Issa M, Zadvornova Y, Naik AS, et al. High rates of escalation and termination of adalimumab therapy and patients exposed to infliximab. Gastroenterology. 2011;140:588.Google Scholar
- 99.Naik AS, Qumseya B, Ananthakrishnan AN, et al. W1102 Anti-TNF therapy for Crohn’s disease: predictors of dose escalation and early discontinuation by 1 year of therapy. Gastroenterology. 2009;136:654.Google Scholar
- 100.Rubin DT, Sederman R. 959 Maintenance of response to biologic therapy in Crohn’s disease is improved with “early use” v. “step up” treatment using health claims data. Gastroenterology. 2009;136:A-146.Google Scholar
- 101.Plevy S, Lu M, Yu A, et al. Observational study of treatment patterns in patients newly initiated with adalimumab or infliximab therapy for Crohn’s disease. Am J Gastroenterol. 2009;104:S479.Google Scholar
- 107.Moore C, Corbett G, Moss AC. Systematic review and meta-analysis: serum infliximab levels during maintenance therapy and outcomes in inflammatory bowel disease. J Crohns Colitis 2016.Google Scholar