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

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World Journal of Gastroenterology 2022年第23期28卷 2597-2608页

作者： Bonita Gu Kavya Venkatesh Astrid-Jane Williams Watson Ng Crispin Corte ali gholamrezaei Simon Ghaly Wei Xuan Sudarshan Paramsothy Susan Connor South Western Sydney Clinical School University of New South WalesSydney 2170New South WalesAustralia Department of Gastroenterology and Hepatology Liverpool HospitalSydney 2170New South WalesAustralia AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred HospitalSydney 2050New South WalesAustralia Department of Medicine University of NewcastleNewcastle 2308New South WalesAustralia Central Clinical School University of SydneySydney 2050New South WalesAustralia Ingham Institute of Applied Medical Research Sydney 2170New South WalesAustralia Department of Gastroenterology St Vincent’s Hospital SydneySydney 2010New South WalesAustralia St Vincent’s Clinical School University of New South WalesSydney 2010New South WalesAustralia Department of Gastroenterology and Hepatology Concord Repatriation General HospitalSydney 2139New South WalesAustralia Concord Clinical School University of SydneySydney 2139New South WalesAustralia

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,t test or Mann-Whitney U 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)vs 3.0(0.3-6.2)mg/L,P=0.003;adalimumab:9.2(6.5-12.0)vs 5.4(2.5-8.3)mg/L,P=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

关键词： Crohn’s disease Perianal disorders Biologics Inflammatory bowel disease

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