Abstract
Background
Anti-TNF α agents, including infliximab (IFX) and adalimumab (ADA), are arguably the most effective medical therapies for fistulising perianal Crohn’s disease (CD). Increased rates of perianal fistula healing have been reported with increased IFX trough levels. Our study aimed to determine the correlation between perianal fistula healing and closure with IFX and ADA trough levels in fistulising perianal CD patients on maintenance therapy.
Methods
In this multi-centre retrospective cross-sectional study, we identified CD patients with perianal fistulae on maintenance IFX or ADA who had an IFX or ADA trough level within 3 months of clinical assessment. Data collected included demographics, serum IFX and ADA trough levels (mg/l) and concomitant medical and surgical therapy. The primary outcome was fistula healing, defined as a cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing as well as closure of all external fistula openings. Receiver operating characteristic (ROC) curve analysis was performed to identify the IFX and ADA concentration cut-off points with combined maximal sensitivity and specificity that corresponded to fistula healing.
Results
A total of 123 patients (IFX = 72; ADA = 51) were included. Fifty-four (75.0%) patients on maintenance IFX achieved fistula healing and 22 (30.6%) achieved fistula closure. Patients who achieved fistula healing had significantly higher median IFX trough levels compared with patients who did not [6.2 (interquartile range 3.1 - 9.6) vs. 3.0 (0.3 - 6.2), (p = 0.007)]. The median IFX trough levels for patients with and without fistula closure were not significantly different [6.4 (2.9 - 9.8) vs. 4.9 (2.5 - 8.9), (p = 0.277)]. Forty (78.4%) patients on maintenance ADA achieved fistula healing and eighteen (35.3%) fistula closure. Patients who achieved fistula healing had a significantly higher median ADA level compared with those who did not [8.7 (6.6 - 12.0) vs. 5.4 (2.5 - 8.3), p = 0.007]. The median ADA trough levels for patients with fistula closure and without fistula closure were not significantly different [9.6 (6.7 – 12.0) vs. 7.7 (4.4–9.8), p = 0.098]. An IFX cut off point of 6.10mg/l was associated with healing (sensitivity 52%; specificity 78%; area under the curve (AUC) 0.72). An ADA cut off point of 7.05mg/l was associated with healing (sensitivity 70%; specificity 73%; AUC 0.77).
Conclusion
Higher IFX and ADA trough levels are associated with fistula healing. No association between IFX and ADA trough levels and fistula closure was seen, although larger numbers may be required. To the best our knowledge, this is the first study to demonstrate a significant association with both higher IFX and ADA levels with fistula healing in perianal CD.
Faculty Opinions recommendation of Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal crohn's disease in children.
