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P518 Does thromboprophylaxis in ulcerative colitis work? Data from the UK IBD audit
Clinical: Therapy and observation Methods: We conducted a prospective study of 37 patients with inflammatory bowel disease (IBD) who received anti TNF alpha therapy in the Department of Gastroenterology of a tertiary hospital, from Romania. Eleven patients diagnosed with IBD who received TB prophylaxis and anti TNF-alpha therapy were compared with a group of 26 patients treated with anti TNF-alpha only. All patients had a tuberculin skin test, a postero-anterior chest plain, and Quantiferon determination. When indicated treatment for latent TB was established 6 months with isoniazid. Results: Of 11 patients who fulfilled the criteria for chemoprophylaxis, none developed active TB after the beginning of anti-TNF-alpha therapy. Eight of these patients had received Infliximab and 3 patients Adalimumab. Remission rate was 72.8% in the first group and 73.6% in the second group. There was no difference in induction and maintaining the remission between the two groups (p = 0.554). There were no hepatic side effects in both groups. Conclusions: TB chemoprophylaxis does not influence the efficacy of anti-TNF alpha therapy in patients with IBD. P516 Efficacy of adalimumab in refractory ulcerative colitis in clinical practice M. Lequoy1 *, P. Seksik2 , Y. Bouhnik3 , M. Allez4 , F. Carbonnel5 , A. Bourrier1 , H. Sokol2 , L. Beaugerie2 , J. Cosnes2 . 1 Hˆ opital Saint Antoine, 75012, Paris, France, 2 Hˆ opital Saint Antoine, Gastro-Ent´ erologie, Paris, France, 3 Hˆ opital Beaujon, 92, Clichy, France, 4 Hˆ opital Saint Louis, 75010, Paris, France, 5 CHU de Bicˆ etre, 94, Le Kremlin-Bicˆ etre, France Background: Controlled trials have demonstrated the efficacy of anti-TNF in ulcerative colitis (UC). Unlike infliximab (IFX), there are limited data with regard to the efficacy of adalimumab (ADA) in clinical practice. The aim of this study was to evaluate the efficacy of ADA for inducing and maintaining remission in patients with refractory UC. Methods: This retrospective and multicentre study included 68 consecutive patients with refractory UC (n = 62) or unclassified colitis (n = 6) treated with ADA between 2006 and 2012 as rescue therapy. 36 of those had lost response to IFX, 14 had developed intolerance, 13 were primary failures, and 13 patients had refused IFX. Study endpoints were achievement of clinical remission (clinical Mayo score [without endoscopy] 2), time-to-clinical recurrence (Kaplan Meier) and time-tocolectomy (Kaplan Meier). In addition, we compared disease course through semesters between 56 patients treated with ADA and 56 patients treated with IFX matched for sex and duration of prior anti-TNF treatment. Results: Among the 63 patients who were active when starting ADA, 40 (63%) achieved clinical remission after a median period of 1 month. Among the 45 patients in clinical remission after induction with ADA (n = 40) or switched from IFX while inactive (n = 5), 32 (71%) were still in remission at 1 year and 26 (58%) at 2 years. Among the total of 68 patients, 14 (21%) underwent colectomy (cumulative rate 34% at 4 years). Predictive factors of colectomy were early disease (p < 0.05), deep ulcerations (p = 0.04), thrombocytosis (p < 0.05) and anemia (p < 0.02). No patient died during the survey. Six (9%) had non serious adverse events. Overall, ADA showed complete efficacy (achievement and/or maintenance of clinical remission along follow-up) in 31 patients (46%). Comparison with patients maintained under IFX showed no significant differences regarding time-to-clinical recurrence, time-to-colectomy, and median values of clinical Mayo score, CRP and hemoglobin. However steroids were used more often in the ADA group (18 on 119 semesters (15%) versus 5 on 197 (3%) in the IFX group; p = 0.03). Conclusions: In clinical practice, ADA is well tolerated and effective as it is able to achieve and maintain clinical remission in about half patients with refractory ulcerative colitis, in
S217 particular in those who had lost response or had developed intolerance to IFX. P517 Evaluating Adalimumab drug and antibody levels as predictors of clinical and laboratory response in Crohn’s disease patients Y. Mazor1 *, U. Koplov2 , D. Ben Hur1 , R. Almog1 , M. Waterman1 , S. Ben-Horin2 , Y. Chowers1 . 1 Rambam Health Care Campus, Department of Gastroenterololgy, Israel, 2 Chaim Sheba Medical Center, Tel Hashomer, Gastroenterology, Tel Aviv, Israel Background: Adalimumab is effective for treatment of Crohn’s disease (CD). Anti-drug antibodies and low trough serum concentrations have been implicated as predisposing factors for treatment failure. We aimed to assess Adalimumab and antiAdalimumab antibody (AAA) serum levels and correlate them with clinical response and serum C-reactive protein (CRP). Methods: Sera from 121 Adalimumab-treated CD patients, with treatment duration of at least 8 weeks, were obtained. Demographic data and clinical response (CR) were recorded and classified as complete, partial or none. Serum Adalimumab and AAA were measured. Receiver operator characteristic (ROC) analysis was preformed to find drug and antibody thresholds for predicting disease activity. Univariate Wilcoxon rank sum tests comparing drug levels, antibody levels, CRP and disease activity were performed. Finally, multivariate regression was utilized to explore the correlation between drug levels, AAA, and disease activity. Results: 161 serum samples were obtained, 94 at trough. Adalimumab >5 mg/ml was predictive of normal CRP (AUC 0.772 for all patients, AUC 0.776 for only trough level measurements, p < 0.005). AAA only did not predict normal CRP or clinical remission, but all patients with trough AAA >5 mg/ml had elevated CRP (RR 16.185, p < 0.005). On multivariate regression, correlation between drug levels, CRP, and clinical response was preserved at AAA levels <5 mg/ml, but not above these levels. Conclusions: Adalimumab serum concentration >5 mg/ml was correlated with normal CRP and CD remission. This correlation is lost when the patient has AAA >5 mg/ ml, suggesting a neutralizing effect of high AAA. P518 Does thromboprophylaxis in ulcerative colitis work? Data from the UK IBD audit R. Lynch1 *, A. Protheroe2 , M. Roughton2 , I. Arnott1 , UK IBD Audit Steering Group2 . 1 NHS Lothian, Gastroenterology, Edinburgh, United Kingdom, 2 RCP, CEEU, London, United Kingdom Background: Venous thromboembolism (VTE) has been long recognised as a complication of inflammatory bowel disease (IBD) with prevalence being reported at between 1.25 and 6.7% and a three-fold increased risk being reported when compared to matched cohorts. It has led to recommendations that all patients admitted with acute flares of ulcerative colitis (UC) should be given prophylactic subcutaneous heparin although data of efficacy in an IBD population are lacking. Methods: Aims: assess the incidence, prophylaxis and possible aetiology of VTE in UC. Methods: we audited 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit. Median age was 42; there were 1421 females and 1628 males. 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. Data collected contained specific questions on the administration of subcutaneous heparin and whether the patient had a thrombotic event during their admission. We also assessed whether type of admission, age,
S218 co-morbidities, disease severity, surgical operations, gender, steroid therapy and treatment response were related to VTE. Results: 2668/3049 (87.5%) patients were given prophylactic heparin. 66/3049 (2.2%) patients experienced VTE during their admission. The rate of VTE amongst heparinised patients, 2.2% (59/2668), did not differ significantly when compared to a rate of 1.8% (7/381) within the population who didn’t receive prophylaxis (p < 0.8). VTE was associated with surgery: 39.4% (26/66) of patients with VTE underwent surgery compared with surgery in 26.2% (781/2983) without VTE (P < 0.02). Of these 26 surgical patients within the VTE population, 4 of these patients’ VTE were post-operative. When patients undergoing elective surgery are excluded VTE is associated with co-morbidity: 46.0% (23/50) of the VTE population compared to 32.4% (810/2504) in the nonVTE population (p < 0.03). There was no association of VTE with disease severity or the use of steroids. Conclusions: Although there was no difference in the frequency of VTE in patients given or not given heparin the numbers of VTE within this group are small. This analysis does however demonstrate that patients with co-morbidity and those undergoing surgery are at higher risk of VTE. Additional measures to prevent VTE should be considered in these patients such as a combination of heparin and compression stockings. All IBD patients admitted to hospital should continue to receive prophylactic subcutaneous heparin. P519 Efficacy of Adalimumab in children and adolescents with moderate/ severe ulcerative colitis E. Volonaki1 *, M. Martins1 , L. Cococcioni1 , M. Malamisura1 , N. Shah1 , K. Lindley1 , F. Kiparissi1 , M. Elawad1 . 1 Great Ormond Street Hospital, Paediatric Gastroenterology, London, United Kingdom Background: Adalimumab is licensed for treating moderately to severely active ulcerative colitis (UC) in adults whose condition has responded inadequately to conventional therapy, but data on its role in paediatric UC are lacking. The aim of our study was to evaluate the efficacy of Adalimumab used as indicated above in children and adolescents treated in a single tertiary UK centre. Methods: All patients with UC who received Adalimumab between April 2008 and October 2012 in our hospital were identified. Clinical response and long term outcomes were assessed. Results: Ten patients (7 females) with median age 14 years (6.8y-16.6y) at the time of first Adalimumab injection were included in our study, with median follow up 1.9 years (1y3y). All patients had failed Infliximab after 6.5 months median duration of treatment (2 24 months). Three patients (3/10, 30%) showed sustained clinical response to Adalimumab with histological evidence of mucosal healing (follow up 16, 22 and 24months respectively). All three received concurrent treatment with Azathioprine or Methotrexate and one of them was successfully weaned off Adalimumab after 21 months, without relapse to date. For the remaining 7 patients, medical treatment was escalated with other immunosuppressive agents, with 4 of them ending up with colectomy (4/10, 40%). Conclusions: Adalimumab was efficacious in 30% of children and adolescents with moderate/ severe ulcerative colitis who failed Infliximab and should therefore be considered as treatment option in refractory disease in this age group.
Poster presentations P520 Efficacy and safety of leucocytapheresis for active inflammatory bowel disease during pregnancy: therapeutic outcomes in four pregnant cases H. Kinoshita1 *, R. Kunisaki1 , S. Tomohiko1 , H. Kimura1 , S. Maeda2 . 1 Yokohama City University Medical Center, Inflammatory Bowel Disease Center, Yokohama, Japan, 2 Yokohama City University, Department of Gastroenterology, Yokohama, Japan Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), affects patients who are in their reproductive age. The benefits of maintaining remission before and during pregnancy overweigh the risks of disease flare-ups and associated adverse effects of drug-based medications on the pregnancy outcome. Although most of the medications used to treat IBD appear to be safe during gestation, patients and their partners are still concerned about the influences of medications on fertility and pregnancy. Therapeutic leucocytapheresis is an alternative to conventional drug therapy. Here we report 4 cases of pregnant IBD patients safely treated with either leucocytapheresis (LCAP) or granulocyte/monocyte apheresis (GMA). Methods: Four pregnant IBD patients, three with UC and one with CD, were treated with therapeutic leucocytapheresis. One patient with UC was treated with LCAP and the other three were treated with GMA. One patient had contraindication to corticosteroids and the other three had corticosteroid refractory IBD. Anticoagulation during the procedure was achieved with heparin in three patients, and with nafamostat mesylate in one patient (LCAP). Results: All four patients responded to therapeutic leucocytapheresis. Two of the three patients with UC achieved steroid free remission before the delivery. Steroid dose was tapered to 5 mg/day in the other patient with UC. In the only CD patient, the symptoms improved, but were not sustained. All three patients with UC delivered healthy babies via uncomplicated vaginal delivery. In the patient with persistently active CD, delivery was carried out by caesarean section at week 36 due to non-reassuring foetal status and the birth weight was 1534g. No adverse effect related to therapeutic leucocytapheresis was observed in these four cases. Conclusions: In these 4 cases, therapeutic leucocytapheresis was safe and was associated with remission in all three cases with active UC. Additionally, with therapeutic leucocytapheresis, corticosteroid sparing is possible, which is highly desirable in pregnant cases. Regarding CD, we believe a study in larger cohort of pregnant patients is warranted for assessing the efficacy of this non-pharmacologic intervention in this clinical setting. P521 Efficacy and safety of adalimumab in children with Crohn’s disease previously treated with infliximab A. Jacob1 *, M. Fumery2 , J. Salleron3 , L. Michaud1 , C. Spyckerelle4 , J.-F. Colombel5 , C. Gower-Rousseau6 , D. Turck1 . 1 University Hospital, Pediatric Unit, Lille, France, 2 Amiens University and Hospital, Gastroenterology, Amiens, France, 3 University Hospital EA 2694, Biostatistics, Lille, France, 4 St Vincent Hospital, Paediatric Unit, Lille, France, 5 University Hospital, Gastroenterology, Lille, France, 6 University Hospital, Epidemiology EA 2694, Lille, France Background: Adalimumab (ADA) is effective in the treatment of Crohn’s disease (CD) in children naive to infliximab (IFX) [1]. The objective of this study was to evaluate the effectiveness and safety of ADA in children with CD refractory or intolerant to IFX. Methods: This retrospective study included all children with CD from a paediatric-onset population-based cohort who received
S217 particular in those who had lost response or had developed intolerance to IFX. P517 Evaluating Adalimumab drug and antibody levels as predictors of clinical and laboratory response in Crohn’s disease patients Y. Mazor1 *, U. Koplov2 , D. Ben Hur1 , R. Almog1 , M. Waterman1 , S. Ben-Horin2 , Y. Chowers1 . 1 Rambam Health Care Campus, Department of Gastroenterololgy, Israel, 2 Chaim Sheba Medical Center, Tel Hashomer, Gastroenterology, Tel Aviv, Israel Background: Adalimumab is effective for treatment of Crohn’s disease (CD). Anti-drug antibodies and low trough serum concentrations have been implicated as predisposing factors for treatment failure. We aimed to assess Adalimumab and antiAdalimumab antibody (AAA) serum levels and correlate them with clinical response and serum C-reactive protein (CRP). Methods: Sera from 121 Adalimumab-treated CD patients, with treatment duration of at least 8 weeks, were obtained. Demographic data and clinical response (CR) were recorded and classified as complete, partial or none. Serum Adalimumab and AAA were measured. Receiver operator characteristic (ROC) analysis was preformed to find drug and antibody thresholds for predicting disease activity. Univariate Wilcoxon rank sum tests comparing drug levels, antibody levels, CRP and disease activity were performed. Finally, multivariate regression was utilized to explore the correlation between drug levels, AAA, and disease activity. Results: 161 serum samples were obtained, 94 at trough. Adalimumab >5 mg/ml was predictive of normal CRP (AUC 0.772 for all patients, AUC 0.776 for only trough level measurements, p < 0.005). AAA only did not predict normal CRP or clinical remission, but all patients with trough AAA >5 mg/ml had elevated CRP (RR 16.185, p < 0.005). On multivariate regression, correlation between drug levels, CRP, and clinical response was preserved at AAA levels <5 mg/ml, but not above these levels. Conclusions: Adalimumab serum concentration >5 mg/ml was correlated with normal CRP and CD remission. This correlation is lost when the patient has AAA >5 mg/ ml, suggesting a neutralizing effect of high AAA. P518 Does thromboprophylaxis in ulcerative colitis work? Data from the UK IBD audit R. Lynch1 *, A. Protheroe2 , M. Roughton2 , I. Arnott1 , UK IBD Audit Steering Group2 . 1 NHS Lothian, Gastroenterology, Edinburgh, United Kingdom, 2 RCP, CEEU, London, United Kingdom Background: Venous thromboembolism (VTE) has been long recognised as a complication of inflammatory bowel disease (IBD) with prevalence being reported at between 1.25 and 6.7% and a three-fold increased risk being reported when compared to matched cohorts. It has led to recommendations that all patients admitted with acute flares of ulcerative colitis (UC) should be given prophylactic subcutaneous heparin although data of efficacy in an IBD population are lacking. Methods: Aims: assess the incidence, prophylaxis and possible aetiology of VTE in UC. Methods: we audited 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit. Median age was 42; there were 1421 females and 1628 males. 202 Sites audited a median of 18 UC patients per site that were admitted with IBD between 1/09/09 and 31/08/10. Data collected contained specific questions on the administration of subcutaneous heparin and whether the patient had a thrombotic event during their admission. We also assessed whether type of admission, age,
S218 co-morbidities, disease severity, surgical operations, gender, steroid therapy and treatment response were related to VTE. Results: 2668/3049 (87.5%) patients were given prophylactic heparin. 66/3049 (2.2%) patients experienced VTE during their admission. The rate of VTE amongst heparinised patients, 2.2% (59/2668), did not differ significantly when compared to a rate of 1.8% (7/381) within the population who didn’t receive prophylaxis (p < 0.8). VTE was associated with surgery: 39.4% (26/66) of patients with VTE underwent surgery compared with surgery in 26.2% (781/2983) without VTE (P < 0.02). Of these 26 surgical patients within the VTE population, 4 of these patients’ VTE were post-operative. When patients undergoing elective surgery are excluded VTE is associated with co-morbidity: 46.0% (23/50) of the VTE population compared to 32.4% (810/2504) in the nonVTE population (p < 0.03). There was no association of VTE with disease severity or the use of steroids. Conclusions: Although there was no difference in the frequency of VTE in patients given or not given heparin the numbers of VTE within this group are small. This analysis does however demonstrate that patients with co-morbidity and those undergoing surgery are at higher risk of VTE. Additional measures to prevent VTE should be considered in these patients such as a combination of heparin and compression stockings. All IBD patients admitted to hospital should continue to receive prophylactic subcutaneous heparin. P519 Efficacy of Adalimumab in children and adolescents with moderate/ severe ulcerative colitis E. Volonaki1 *, M. Martins1 , L. Cococcioni1 , M. Malamisura1 , N. Shah1 , K. Lindley1 , F. Kiparissi1 , M. Elawad1 . 1 Great Ormond Street Hospital, Paediatric Gastroenterology, London, United Kingdom Background: Adalimumab is licensed for treating moderately to severely active ulcerative colitis (UC) in adults whose condition has responded inadequately to conventional therapy, but data on its role in paediatric UC are lacking. The aim of our study was to evaluate the efficacy of Adalimumab used as indicated above in children and adolescents treated in a single tertiary UK centre. Methods: All patients with UC who received Adalimumab between April 2008 and October 2012 in our hospital were identified. Clinical response and long term outcomes were assessed. Results: Ten patients (7 females) with median age 14 years (6.8y-16.6y) at the time of first Adalimumab injection were included in our study, with median follow up 1.9 years (1y3y). All patients had failed Infliximab after 6.5 months median duration of treatment (2 24 months). Three patients (3/10, 30%) showed sustained clinical response to Adalimumab with histological evidence of mucosal healing (follow up 16, 22 and 24months respectively). All three received concurrent treatment with Azathioprine or Methotrexate and one of them was successfully weaned off Adalimumab after 21 months, without relapse to date. For the remaining 7 patients, medical treatment was escalated with other immunosuppressive agents, with 4 of them ending up with colectomy (4/10, 40%). Conclusions: Adalimumab was efficacious in 30% of children and adolescents with moderate/ severe ulcerative colitis who failed Infliximab and should therefore be considered as treatment option in refractory disease in this age group.
Poster presentations P520 Efficacy and safety of leucocytapheresis for active inflammatory bowel disease during pregnancy: therapeutic outcomes in four pregnant cases H. Kinoshita1 *, R. Kunisaki1 , S. Tomohiko1 , H. Kimura1 , S. Maeda2 . 1 Yokohama City University Medical Center, Inflammatory Bowel Disease Center, Yokohama, Japan, 2 Yokohama City University, Department of Gastroenterology, Yokohama, Japan Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), affects patients who are in their reproductive age. The benefits of maintaining remission before and during pregnancy overweigh the risks of disease flare-ups and associated adverse effects of drug-based medications on the pregnancy outcome. Although most of the medications used to treat IBD appear to be safe during gestation, patients and their partners are still concerned about the influences of medications on fertility and pregnancy. Therapeutic leucocytapheresis is an alternative to conventional drug therapy. Here we report 4 cases of pregnant IBD patients safely treated with either leucocytapheresis (LCAP) or granulocyte/monocyte apheresis (GMA). Methods: Four pregnant IBD patients, three with UC and one with CD, were treated with therapeutic leucocytapheresis. One patient with UC was treated with LCAP and the other three were treated with GMA. One patient had contraindication to corticosteroids and the other three had corticosteroid refractory IBD. Anticoagulation during the procedure was achieved with heparin in three patients, and with nafamostat mesylate in one patient (LCAP). Results: All four patients responded to therapeutic leucocytapheresis. Two of the three patients with UC achieved steroid free remission before the delivery. Steroid dose was tapered to 5 mg/day in the other patient with UC. In the only CD patient, the symptoms improved, but were not sustained. All three patients with UC delivered healthy babies via uncomplicated vaginal delivery. In the patient with persistently active CD, delivery was carried out by caesarean section at week 36 due to non-reassuring foetal status and the birth weight was 1534g. No adverse effect related to therapeutic leucocytapheresis was observed in these four cases. Conclusions: In these 4 cases, therapeutic leucocytapheresis was safe and was associated with remission in all three cases with active UC. Additionally, with therapeutic leucocytapheresis, corticosteroid sparing is possible, which is highly desirable in pregnant cases. Regarding CD, we believe a study in larger cohort of pregnant patients is warranted for assessing the efficacy of this non-pharmacologic intervention in this clinical setting. P521 Efficacy and safety of adalimumab in children with Crohn’s disease previously treated with infliximab A. Jacob1 *, M. Fumery2 , J. Salleron3 , L. Michaud1 , C. Spyckerelle4 , J.-F. Colombel5 , C. Gower-Rousseau6 , D. Turck1 . 1 University Hospital, Pediatric Unit, Lille, France, 2 Amiens University and Hospital, Gastroenterology, Amiens, France, 3 University Hospital EA 2694, Biostatistics, Lille, France, 4 St Vincent Hospital, Paediatric Unit, Lille, France, 5 University Hospital, Gastroenterology, Lille, France, 6 University Hospital, Epidemiology EA 2694, Lille, France Background: Adalimumab (ADA) is effective in the treatment of Crohn’s disease (CD) in children naive to infliximab (IFX) [1]. The objective of this study was to evaluate the effectiveness and safety of ADA in children with CD refractory or intolerant to IFX. Methods: This retrospective study included all children with CD from a paediatric-onset population-based cohort who received