Systematic Review and Meta-Analysis: Serum Infliximab Levels During Maintenance Therapy and Outcomes in Inflammatory Bowel Disease

Abstract

Background and aims: A number of observational studies have reported an association between serum levels of infliximab [IFX] at various thresholds, and clinical outcomes in inflammatory bowel disease [IBD]. This association has not previously been systematically analysed.

Methods: Systematic review of studies that reported serum infliximab levels according to outcomes in IBD. Primary outcome was clinical remission, and secondary outcomes included endoscopic remission, C-reactive protein [CRP] levels, and colectomy. Meta-analysis of raw data was performed where appropriate. A quality assessment was also undertaken.

Results: A total of 22 studies met the inclusion criteria, including 3483 patients; 12 studies reported IFX levels in a manner suitable for determining effect estimates. During maintenance therapy, patients in clinical remission had significantly higher mean trough IFX levels than patients not in remission: 3.1 µg/ml versus 0.9 µg/ml. The standardised mean difference in serum IFX levels between groups was 0.6 µg/ml (95% confidence interval [CI] 0.4-0.9, p = 0.0002]. Patients with an IFX level > 2 µg/ml were more likely to be in clinical remission (risk ratio [RR] 2.9, 95% CI 1.8-4.7, p < 0.001], or achieve endoscopic remission [RR 3, 95% CI 1.4-6.5, p = 0.004] than patients with levels < 2 µg/ml.

Conclusions: There is a significant difference between serum infliximab levels in patients with IBD in remission, compared with those who relapse. A trough threshold during maintenance > 2 µg/ml is associated with a greater probability of clinical remission and mucosal healing.

Keywords: Infliximab; mucosal healing; remission; trough.

Figure 1.

Forest plot of standardized mean difference [SMD] by inverse variance method [random effects model].

Figure 2.

Mean and standard deviation [SD] of serum infliximab [IFX] level in each study grouped by clinical status.

Figure 3.

Risk ratio of clinical remission grouped by serum infliximab [IFX] cut-off [2 µg/ml]. Random effect, Maentel-Haenszel ratio.

Figure 4.

Risk ratio of mucosal healing grouped by serum infliximab [IFX] cut-off [2 µg/ml]. Random effect, Maentel-Haenszel ratio.

Figure 5.

Mean and standard deviation [SD] of serum C-reactive protein [CRP] level in patients with an infliximab [IFX] level < 3 µg/ml, and those with an IFX > 2 µg/ml.