Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn's disease.

Background: Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing.

Aim: To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels.

Methods: In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, test or Mann-Whitney test.

Results: One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) 3.0 (0.3-6.2) mg/L, = 0.003; adalimumab: 9.2 (6.5-12.0) 5.4 (2.5-8.3) mg/L, = 0.004]. For patients on infliximab, fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age. For patients on adalimumab, fistula healing was associated with higher rates of combination therapy with an immunomodulator. Serum trough levels for patients with and without fistula closure were not significantly different for infliximab [6.9 (4.3-10.2) 5.5 (2.5-8.3) mg/L, = 0.105] or adalimumab [10.0 (6.6-12.0) 7.8 (4.2-10.0) mg/L, = 0.083].

Conclusion: Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.