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P438 Intolerance to IBD treatment in over 1,800 patients in the Oxford IBD Cohort
Clinical: Therapy & observation Conclusions: IBD patients with IDA, who had been unsuccessfully treated with oral iron, had very poor baseline HRQOL scores. Treatment with FER resulted in a substantial increase in Hgb and decrease in fatigue, with a safety profile similar to the overall IDA population. P438 Intolerance to IBD treatment in over 1,800 patients in the Oxford IBD Cohort A. Kent *, H. Gray-Stephens, A.-M. Castaneanu, J. Brooks, P. Siddhanathi, S. Travis, H. Uhlig, S. Keshav. Oxford University Hospitals Trust, Translational Gastroenterology Unit, Oxford, United Kingdom Background: Managing inflammatory bowel disease (IBD) typically requires long-term medication, including combination therapy. Side effects are widely recognised, however the rate is usually evaluated only for individual drugs. Methods: Retrospective data from 1889 patients consented to the Oxford IBD cohort study (REC 09/H1204/30) was used to evaluate intolerance. Entries in the Oxford IBD research database were confirmed by review of the medical record. Results: 52% patients were female and 50% had Crohn’s Disease (CD). 353 (19%) of all patients reported 538 intolerances, with CD accounting for 61%. 88 (5%) reported intolerance to 2 drugs, 28 (2%) to 3 drugs and 11 (1%) to 4 drugs. Immunomodulator drugs (IMDs): 61% of intolerances were to thiopurines. 255 (42%) of patients treated with azathioprine (AZA) were intolerant & 120 of these were switched to 6-mercaptopurine (6-MP). Of these, 62 (52%) were intolerant of 6-MP. Specific conditions requiring AZA/6-MP withdrawal included leucopenia (56, 10%), deranged liver chemistry (36, 6%), pancreatitis (19, 3%) and single cases of nodular regenerative hyperplasia & haemophagocytic syndrome secondary to EBV. 22% of patients treated with methotrexate (MTX) were intolerant and intolerance increased if there had been previous intolerance to AZA (32%) or 6-MP (42%). Anti-TNF therapy (ATT): 15% of 433 patients treated with ATT reported intolerance, 18% to infliximab (IFX) and 9% to adalimumab (ADA). In patients with a preceding intolerance to AZA, 24/96 (25%) were intolerant to IFX and 7/53 (13%) were intolerant to ADA. 68% of intolerance were in women. 23 patients treated with ADA had previously reacted to IFX & 3 patients on IFX had reacted to ADA. 118 patients had been treated sequentially with IFX and ADA, and only 7 were intolerant to both. Specific intolerances that required therapy withdrawal included hypersensitivity (28 cases), and single reports of peripheral neuropathy, pneumonitis and dilated cardiomyopathy with IFX, and transient weakness, tuberculosis, psoriaform rash, peripheral neuropathy and angioedema with ADA. Other medications: Prednisolone & 5-aminosalicylates (5-ASA) had less reported intolerance. They included 4 cases of psychosis on corticosteroids and single cases of acute liver failure and neuropathy with 5-ASA. This probably reflects recording bias towards substantive events on common therapy. Conclusions: Intolerance to IBD therapy is common, but rarely life-threatening. Half of patients intolerant of AZA were intolerant of 6-MP, and a third intolerant of MTX. Any intolerance of an IMD was associated with a 20% risk of intolerance to ATT. Reported intolerance was less frequent with ADA than IFX, and prior intolerance to IMDs was not associated with increased risk of intolerance to ADA.
S249 P439 In patients with Crohn’s disease, timing of switching from infliximab to adalimumab affects prognosis K. Takeuchi *, A. Yamada, Y. Suzuki. Toho University, Sakura Medical Centre, Division of Gastroenterology, Department of Internal Medicine, Sakura, Japan Background: Patients with Crohn’s disease (CD) under infliximab (IFX) maintenance therapy, at some time point may require dose escalation or shortening of infusion interval to maintain an adequate efficacy level due to loss of response. Switching from IFX to adalimumab (ADA) has been considered as one therapeutic option for avoiding adverse side effects and overcoming the loss of response phenomena, but hitherto, the most appropriate time point for this change over has not been reported. With this in mind, we became interested to determine a clinically relevant timing of switching from IFX to ADA in CD patients who had developed active disease in spite of IFX dose escalation or shortened infusion interval. Methods: In this endeavour, we retrospectively reviewed CD patients who had received either IFX dose escalation/shortened infusion interval or switched from IFX at 5 mg/kg/bodyweight to ADA. All patients had developed active CD while under IFX maintenance therapy at 5 mg/kg/bodyweight. Patients were divided into switch group and IFX dose escalation group (IFX 5 mg/kg to 10 mg/kg or shortened infusion interval). The final observation time was week 52 when efficacy outcomes in the two groups were compared. Results: A total of 74 patients with CD were included in this study, switch group 15 patients and dose escalation group 59 patients. Three of 15 patients had switched to ADA because of IFX infusion reaction. An 11 of 15 patients (73%) in the switch group together with 35 of 59 patients (59%) in the IFX dose escalate group could continue the treatment up to week 52, all in clinical remission. Further, at week 52, C-reactive protein in the switch group was significantly lower than in the IFX dose escalation group, 0.28±0.387 mg/dL vs 1.13±1.640 mg/dL, respectively (P = 0.009). Conclusions: In CD patients with the loss of response to IFX, switching to ADA before IFX dose escalation appears to be a clinically relevant therapeutic decision. Potentially, this finding should minimize futile use of IFX and reduce morbidity time for many patients. P440 Influence of induction therapy with infliximab on histological changes in children with ulcerative colitis preliminary data S. Szymanska1 *, A. Wiernicka2 , J. Cielecka-Kuszyk1 , E. Szymanska2 , M. Dadalski2 , J. Kierkus2 . 1 The Children’s Memorial Health Institute, Pathology, Warsaw, Poland, 2 The Children’s Memorial Health Institute, Gastroenterology, Hepatology and Feeding Disorders, Warsaw, Poland Background: Infliximab (IFX) is an effective therapy in inflammatory bowel disease (IBD). Most data proved its clinical efficacy and very little is known about the influence on histology, specially in children with ulcerative colitis (UC). The aim of this study was to verify the impact of induction therapy with IFX on histopathological changes in children with UC. Methods: Sixteen children with active UC were enrolled to this study. Colonoscopy with collected samples was performed in all patients before and after three injections of IFX. PUCAI index was used to assess clinical condition of the subjects, endoscopic features were classified according to Baron scale, disease location was classified according to Paris Classification and histological changes were precisely described according to protocol of The British Society of Gastroenterology. The condition of each patient before and after induction therapy with IFX was compared with special focus on histological changes.
S249 P439 In patients with Crohn’s disease, timing of switching from infliximab to adalimumab affects prognosis K. Takeuchi *, A. Yamada, Y. Suzuki. Toho University, Sakura Medical Centre, Division of Gastroenterology, Department of Internal Medicine, Sakura, Japan Background: Patients with Crohn’s disease (CD) under infliximab (IFX) maintenance therapy, at some time point may require dose escalation or shortening of infusion interval to maintain an adequate efficacy level due to loss of response. Switching from IFX to adalimumab (ADA) has been considered as one therapeutic option for avoiding adverse side effects and overcoming the loss of response phenomena, but hitherto, the most appropriate time point for this change over has not been reported. With this in mind, we became interested to determine a clinically relevant timing of switching from IFX to ADA in CD patients who had developed active disease in spite of IFX dose escalation or shortened infusion interval. Methods: In this endeavour, we retrospectively reviewed CD patients who had received either IFX dose escalation/shortened infusion interval or switched from IFX at 5 mg/kg/bodyweight to ADA. All patients had developed active CD while under IFX maintenance therapy at 5 mg/kg/bodyweight. Patients were divided into switch group and IFX dose escalation group (IFX 5 mg/kg to 10 mg/kg or shortened infusion interval). The final observation time was week 52 when efficacy outcomes in the two groups were compared. Results: A total of 74 patients with CD were included in this study, switch group 15 patients and dose escalation group 59 patients. Three of 15 patients had switched to ADA because of IFX infusion reaction. An 11 of 15 patients (73%) in the switch group together with 35 of 59 patients (59%) in the IFX dose escalate group could continue the treatment up to week 52, all in clinical remission. Further, at week 52, C-reactive protein in the switch group was significantly lower than in the IFX dose escalation group, 0.28±0.387 mg/dL vs 1.13±1.640 mg/dL, respectively (P = 0.009). Conclusions: In CD patients with the loss of response to IFX, switching to ADA before IFX dose escalation appears to be a clinically relevant therapeutic decision. Potentially, this finding should minimize futile use of IFX and reduce morbidity time for many patients. P440 Influence of induction therapy with infliximab on histological changes in children with ulcerative colitis preliminary data S. Szymanska1 *, A. Wiernicka2 , J. Cielecka-Kuszyk1 , E. Szymanska2 , M. Dadalski2 , J. Kierkus2 . 1 The Children’s Memorial Health Institute, Pathology, Warsaw, Poland, 2 The Children’s Memorial Health Institute, Gastroenterology, Hepatology and Feeding Disorders, Warsaw, Poland Background: Infliximab (IFX) is an effective therapy in inflammatory bowel disease (IBD). Most data proved its clinical efficacy and very little is known about the influence on histology, specially in children with ulcerative colitis (UC). The aim of this study was to verify the impact of induction therapy with IFX on histopathological changes in children with UC. Methods: Sixteen children with active UC were enrolled to this study. Colonoscopy with collected samples was performed in all patients before and after three injections of IFX. PUCAI index was used to assess clinical condition of the subjects, endoscopic features were classified according to Baron scale, disease location was classified according to Paris Classification and histological changes were precisely described according to protocol of The British Society of Gastroenterology. The condition of each patient before and after induction therapy with IFX was compared with special focus on histological changes.