DOP035 High gammaglobulin and low albumin serum levels independently predict secondary loss of response to anti-TNFα therapy in IBD

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Abstract

Background: Loss of response to biological therapy with anti- TNFα drugs occurs frequently in patients with IBD. Possible markers to predict sustained treatment success are currently under investigation. We evaluated the predictive value of serum albumin and gammaglobulin levels for the success of an anti-TNFα treatment in IBD.

Methods: In a prospective trial we included all patients treated with either infliximab or adalimumab for IBD in our outpatient clinic between 2007 and 2015. Secondary loss of response (SLR) was defined as the necessity to increase the dose or to reduce treatment intervals after an initial response to therapy. In addition, trough levels of adalimumab or infliximab and anti- drug antibody concentrations have been measured since they were available. Prior to the initiation of biological treatment all patients were tested for serum- albumin and serum- gammaglobulin levels.

Results: 82 patients (42 female, 40 male; age 39.5±13.5 years) were included in the study. 65 patients with Crohn's disease and 17 patients with ulcerative colitis. Of these patients 66 (80.5%) were treated with infliximab and 16 (19.5%) received adalimumab first line. 7 patients (8.5%) were primary non responders, 29 patients (35.4%) showed a sustained remission under treatment and 46 patients (56.1%) developed a SLR. Of these, 11 patients (23.9%) experienced loss of response within the first year of treatment, 14 patients (30.4%) during the second year of treatment and 21 patients (45.7%) after more than two years of treatment (Mean time to SLR 25.7±16.1 months). Albumin levels in the sustained response group were significantly higher compared to SLR (37.6±1.3 g/dl vs. 34.4±0.7 g/dl; p<0.05). Gammaglobulin levels in the sustained response group were significantly lower compared to SLR (12.8±0.9 g/dl vs. 17.41±0.9 g/dl; p=0.001). Hypoalbuminemia and/or hypergammaglobulinemia were independently associated to the loss of response.

Conclusions: Our study supports previous investigations showing that low albumin levels at the beginning of an anti-TNFα therapy are strongly associated to treatment failure. To our knowledge, this is the first report to show that increased gammaglobulin levels prior to the initiation of a biological therapy in IBD are independently associated and predictive to identify patients with a higher risk for loss of response to an anti-TNFα treatment. Increased serum gammaglobulines represent a higher B-cell activity with either a higher risk to produce anti-drug antibodies, a different phenotype of disease less responsive to anti-TNFα treatment or both.

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