Short summary

The purpose of this descriptive study is to investigate the correlation between serum concentration of infliximab, infliximab antibodies, and clinical disease course.

Specifically, we want to study this during rescue therapy with infliximab in patients with acute severe ulcerative colitis who has failed treatment with intravenous glucocorticosteroids.

Our hypothesis is that there is a correlation between serum-concentration of IFX during rescue therapy and clinical outcome.

Rationale

Acute severe colitis is a serious condition requiring admission to hospital. In spite of intensive medical therapy, a number of patients will end up having colectomy, and in earlier series, the condition even had mortality. In standard care, patients will be treated with high-dose intravenous glucocorticosteroids and supporting treatment (low-molecular heparin, intravenous fluids, antibiotics etc.).

Current treatment algorithm and international guidelines suggest that patients who have had only a partial response at day 3-5 should be given rescue therapy with biological therapy infliximab (IFX). While IFX reduces the need for colectomy in these patients, a substantial proportion of patients receiving IFX rescue therapy will not respond and will need urgent colectomy. Identifying patients not responding to rescue medical therapy is important in order to improve the outcome in patients with this serious condition.

Therapeutic drug monitoring (TDM) has been proposed as a mean of optimizing response to biologics including IFX. TDM has been most widely used in patients on maintenance therapy showing loss of response to therapy. In this setting, evidence suggests that measurement of drug levels and antibodies to drug is a cost-effective strategy for optimizing treatment Studies have shown a positive correlation between drug levels and outcome, and this has led to the suggestion of increased dosing (accelerated induction, shortening intervals between infusions) of IFX as a means of increasing the likelihood of a favorable response to IFX in steroid refractory acute severe ulcerative colitis (ASUC), thus avoiding colectomy. Although some reports supports the usefulness of accelerated induction in steroid refractory ASUC prospective well-controlled studies are missing.

The aim of this project is to study if there is a correlation between infliximab serum level and the clinical outcome of induction therapy in the setting of rescue treatment of patients with severe ulcerative colitis not responding to intravenous glucocorticosteroids. To establish which serum concentration of infliximab that should be obtained during rescue therapy, to achieve remission and thereby avoid colectomy.

Description of the cohort

Patients with severe ulcerative colitis according to the Modified Truelove and Witts Severity Index Score. Admitted to the in-ward Department of Medical Gastroenterology, Odense University Hospital, Svendborg Hospital or Hospital of South West Jutland in Esbjerg.

Data and biological material

Data includes clinical disease activity, endoscopic findings, standard biochemistry to determine the degree of sickness at admission and basic patient-demographics such as age and gender.

Furthermore, data on disease course will be collected (time of diagnosis, disease extent, disease duration, previous treatment prior to inclusion).

Blood samples will be drawn eight times pr patient for measurements of inflammatory markers, Infliximab and serum anti-infliximab antibodies.

Collaborating researchers and departments

Department of gastroenterology, Odense University Hospital

• Professor, Jens Kjeldsen
• Professor, Mark Ainsworth

Department of gastroenterology, Svendborg Hospital

• Consultant, Ph.D. Claus Aalykke

Department of clinical biochemistry, Svendborg Hospital

• Ph.D. Morten Beck Trelle
• Ph.D. Steen Antonsen

department og gastroenterology, Hospital of South West Jutland

• Professor, Torben Knudsen