S3482 Management of Therapy in a Crohn’s Disease Patient With Secondary Loss of Response to Infliximab

Abstract

INTRODUCTION: Infliximab is a widely-used biological therapy in Crohn’s disease. Up to 40% of patients exhibit loss of response in the first year of therapy. Currently, there is no established guideline based on strong evidence to direct care in such cases. We present a case of a patient with Crohn’s disease who developed secondary loss of response to infliximab therapy. CASE DESCRIPTION/METHODS: A 46 year-old male with a history of Crohn’s disease presented to the office for a follow up visit. Patient was started on infliximab and achieved remission about a year ago after a Crohn’s flare, but started to develop worsening epigastric abdominal pain, fatigue, and joint pain. Colonoscopy revealed acute inflammation in the transverse colon and benign lymphoid aggregates in the descending and rectosigmoid colon. Infliximab trough and anti-drug antibody level were 7.9 µg/mL and 13 AU (≥10 AU indicates detectable serum levels per laboratory guidelines) respectively. Infliximab dosing interval was decreased and 6-mercaptopurine was started. Patient showed resolution of symptoms and repeat blood tests in 3 months revealed increased trough level and undetectable anti-drug antibody level. DISCUSSION: Secondary loss of response is defined as recrudescence of clinically active disease after an initial response. Production of anti-drug antibodies is commonly seen and it is thought to accelerate drug clearance, neutralizing its effects. In such situation, one or combination of the following is suggested – continue current treatment with shortened dosing interval or increased dosing, add an immunomodulator, or switch to another drug within the same class or of another class. There is conflicting evidence regarding benefit of dose escalation especially in the presence of high drug-antibody titer. Switching to another agent may be preferable, but optimizing current therapy should be attempted before doing so, especially given that there are limited treatment options for IBD and patients with high drug-antibody level to infliximab are more likely to poorly respond to an alternative anti-TNF agent. Pre-treatment or co-treatment with an immunomodulator appears to be superior to monotherapy with infliximab, but the benefit in those with secondary loss of response to infliximab alone is unclear. Optimal drug concentration and meaningful drug antibody level should be established and further research should be pursued to guide therapy in patients with secondary loss of response to anti-TNF therapy.