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

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.