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P539. Dose intensification with anti-TNF agents in inflammatory bowel disease – a secondary care experience

G. Kothegal Marimahadevappa1, J.K. Limdi1, 1The Pennine Acute Hospitals NHS Trust, Gastroenterology, Manchester, United Kingdom

Background

The efficacy of anti-TNF therapy, Infliximab (IFX) and Adalimumab (ADA) has been established in pivotal trials for induction and maintenance of remission of inflammatory bowel disease (IBD). Despite this a proportion of patients lose response and require dose intensification. The aim of our study was to assess the efficacy and durability of dose intensification with IFX/ADA.

Methods

A retrospective review of patients with IBD receiving IFX/ADA infusions from October 2011 until April 2012 at our institution was conducted through electronic and case note review, endoscopy, radiology and pathology reports. Patients losing response after 6 months or more of IFX/ADA maintenance therapy and in whom treatment was intensified were included. Dose intensification was defined as an increase in IFX dose per infusion from 5 mg to 10 mg/kg or increase in frequency of infusions from 8 weeks to 5–6 weeks. For ADA this was defined as increasing the dose from 40 mg to 80 mg or increasing the frequency from biweekly to weekly.

A positive response was defined by clinician assessment after 3 infusions. Non-response or loss of response was defined as persistent disease related symptoms requiring steroid therapy, hospitalisation, surgery or discontinuation of IFX/ADA.

Results

Of 208 patients receiving anti TNF therapy (IFX=157, ADA=51), 15 patients (12 female) received dose intensification (IFX=12, ADA=3). 6 had Ulcerative Colitis (UC) (4 pan-colonic, 2 left sided) and 9 had Crohn's Disease (CD) with non stricturing, non penetrating disease (3), active stricturing (3), penetrating (1) and peri-anal (2) disease. Disease location was ileal (1), colonic (2) and ileo-colonic in 6. The median age was 40 years (range 18–72 yrs). 5 patients were current or ex-smokers.

Response to intensification after approximately median duration of follow up of 12 months was noted in 8/9 CD and 2/6 UC patients. 9 patients (60%) remained on dose intensification and 5 lost response (33%). In 1 patient treatment discontinued due to third trimester pregnancy. 2 (UC) were reverted to their previous dose. 2 non-responders underwent surgery and 1 received Methotrexate. 2 are being evaluated for further dose intensification.

Conclusion

A significant proportion of patients with CD respond to dose intensification. Anti-TNF trough and antibody levels, an astute assessment for active disease and search for alternative mechanistic explanations for symptoms are imperative prior to embarking on expensive therapy with its inherent risks.