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P332 Adherence to anti-tumor necrosis factor alpha therapies in inflammatory bowel diseases: Experience from four referral Italian centers
S142 of colectomy and steroid free remission. Disease activity was assessed using the MTWSI. Results: In total, 30 patients have been treated. Median age at diagnosis of UC was 27 years (range 17 69); median age at treatment with IFX was 32.5 years (range 17 74 years). There were 20 male and 10 female patients. 40% of patients had left sided colitis, 50% had pancolitis and the remaining 10% had proctitis. 23 (76.6%) were on an immunomodulator. 1 patient had been previously treated with IFX, 1 failed trial tetomilast, 3 had been treated with visiluzimab and the other 25 were naïve to biologics. CMV was excluded in all but 2 patients. Median duration from diagnosis to IFX was 53.5 months (0 336 months) and the duration of flare before IFX was a median of 1 month (range 0 15). Median dose requirement was 3 infusions (range 1 6). MTWSI on day of infusion: 11 (3 17), day 7: 5 (4 14) and 8 weeks: 3 (0 13). 19 (63.3%) successfully avoided colectomy and 11 (36.7%) patients progressed to surgery. Long term follow up (>12 months) was available for 16 patients who avoided colectomy and all 16 patients remained colectomy free. The median duration from IFX to surgery was 58 days (1 213). Univariate analysis failed to identify predictors of requirement for surgery. In the rescued group 13 (68.4%) remained steroid free. Univariate analysis revealed male gender as the only factor which predicted successful cessation of steroids (OR: 7.5; 95% CI 0.78 78; P = 0.09). Only 3 patients developed complications: 1 steroid induced psychosis, 1 pancreatitis and neutropaenia secondary to thiopurine, and 1 thromboembolic stroke (precipitant unknown). Conclusions: Results from this cohort of patients with severe steroid refractory and steroid dependent UC, indicate that colectomy was avoided in more than 60% of patients when IFX was administered. The long term colectomy rate in this group appears to be lower than historical data on cyclosporine treatment in the same setting. IFX use was also associated with lower rates of long term steroid requirement. There were no identifiable predictive factors for response and need for surgical intervention. P332 Adherence to anti-tumor necrosis factor alpha therapies in inflammatory bowel diseases: Experience from four referral Italian centers E. Angelucci1 *, M. Cesarini2 , A. Cocco3 , M.C. Di Paolo4 , B. Galletti1 , D. De Nitto1 , G. Latella1 , L. Tammaro4 , R. Pica3 , P. Vernia2 , G. Frieri1 . 1 University of L’Aquila, Italy, 2 Sapienza University, Rome, Italy, 3 Ospedale S. Pertini, Italy, 4 Ospedale San Giovanni Addolorata, Italy Background: Non adherence to long-term medical therapy occurs in 30 50% of chronic diseases [1] and in 5 60% of pts with IBD. Aim of this study was to assess adherence to scheduled administration of Infliximab (IFX, 5 10 mg/kg) and Adalimumab (ADA, 80 40 mg) in pts with Crohn’s disease (CD) and ulcerative colitis (UC), from four Italian referral centres. Methods: All pts receiving biologics were included in the study. Cause and length of delay/anticipation respect to scheduled administration were considered. Adherence to ADA was assessed using patient diaries. The mean duration of biological therapy was 16.5 months (1 61). Patients: 136, 60M/76F, 110CD/26UC, mean age at diagnosis 32.4 (20 73) and at 1st administration 40.5 (16 78). IFX was administered to 93/136 pts (68.4%) and ADA to 43/136 (31.6%). Indications to biologicals were: steroid-dependence/resistance in 91/136 (66.9%), fistulae in 35/136 (25.8%), AZA failure in 6/136 (4.4%) others in 4/136 (2.9%). The overall number of administrations was 1763 (mean 12.9/pt, range1 73). Results: A total of 187/1763 administrations (10.6%) in 45 pts (33%) was delayed [29 IFX (32.6%), 16 ADA (43.2%) (p = 0.3)]. The mean number of delayed administrations was 2.2 and
Poster presentations the delay 13.7 days (1 35). Forgetfulness, summer holidays, pharmaceutical supply and intentional non adherence were responsible for 294 days delay (28 pts). Adverse events were responsible for 198 days delay (18 pts). A total of 82/1763 administrations (4.65%) were anticipated in 14 pts (13 on IFX 92.8% and 1 on ADA 7.2% p < 0.01), with a mean of 2.05 events/pt and an anticipation vs scheduled timing of 7.8 days (1 28). The reason for anticipation was related to practical issues in 19 (23.2%), occurrence of articular pain in 1 (1.2%) and lost response/active disease in 62 (75.6%) administrations. A clinical need and not a lack of adherence justify anticipation in these last 62 patients. Conclusions: About 30% of patients failed to adhere strictly to scheduled treatment with biologics, in 10.6% of administrations. Possible consequences of reduced compliance remain to be assessed. Interestingly, in this study lack of adherence has been found also with agents which do not require daily and/or multiple administrations (features associated with low adherence in literature). No difference has been found between IFX and ADA in terms of decreased adherence. Reference(s) [1] World Health Organization. Adherence to long term Therapies. Evidence for action. 2003. P333 Withdrawn P334 Concentration effect relationship of infliximab in Crohn’s disease: Results of a cohort study C. Lamblin1 , A. Aubourg1 *, D. Ternant2 , L. Picon1 , T. Lecomte1 , G. Paintaud2 . 1 CHU Tours, Hepatogastroenterology, Tours, France, 2 Universit´ e Fran¸cois Rabelais, CNRS 6239 GICC, Tours, France Background: Infliximab (IFX) has dramatically changed the management of Crohn’s disease. Although it has a proven efficacy in inducing and maintaining remission, loss of response is frequently observed, requiring optimisation. Previous studies were in favor of the measurement of IFX trough concentrations to help therapeutic decisions. The aim of our study was to study concentration effect relationships of IFX in a cohort of Crohn’s disease patients. Methods: All patients with luminal and/or perineal Crohn’s disease with maintenance IFX treatment followed between January 2007 and June 2010 in the Hepatogastroenterology Department of Tours University Hospital were included. Crohn’s Disease Activity Index (CDAI), serum concentration of C-reactive protein (CRP) and IFX trough concentration were measured prospectively in a routine clinical manner. Other demographic and clinical data were collected retrospectively. Because of a large variability in the number of IFX concentrations per patient, statistical analyses were performed using the nearer steady-state concentration for each patient. Concentration effect relationship modeling used Winnonlin® software (Pharsight corp.). Results: Forty-four patients were included. At the time of analysis, 20 patients were in clinical and biological remission and 24 were in relapse. IFX concentrations were significantly higher in patients in remission than in those relapsing, 6.33 mg/L vs 3.39 mg/L (p < 0.02). No significant association was found between IFX concentrations and concomitant immunosuppressive treatment or presence of antibodies to infliximab. The relationship between CRP and IFX concentrations was best described by an Emax inhibition model: estimated EC50, which is the concentration of infliximab leading to a 50% decrease of CRP concentration, was 1.1 mg/L. According to this model, concentration of CRP below 5 mg/L was obtained by IFX concentrations above 5.6 mg/L.
Poster presentations the delay 13.7 days (1 35). Forgetfulness, summer holidays, pharmaceutical supply and intentional non adherence were responsible for 294 days delay (28 pts). Adverse events were responsible for 198 days delay (18 pts). A total of 82/1763 administrations (4.65%) were anticipated in 14 pts (13 on IFX 92.8% and 1 on ADA 7.2% p < 0.01), with a mean of 2.05 events/pt and an anticipation vs scheduled timing of 7.8 days (1 28). The reason for anticipation was related to practical issues in 19 (23.2%), occurrence of articular pain in 1 (1.2%) and lost response/active disease in 62 (75.6%) administrations. A clinical need and not a lack of adherence justify anticipation in these last 62 patients. Conclusions: About 30% of patients failed to adhere strictly to scheduled treatment with biologics, in 10.6% of administrations. Possible consequences of reduced compliance remain to be assessed. Interestingly, in this study lack of adherence has been found also with agents which do not require daily and/or multiple administrations (features associated with low adherence in literature). No difference has been found between IFX and ADA in terms of decreased adherence. Reference(s) [1] World Health Organization. Adherence to long term Therapies. Evidence for action. 2003. P333 Withdrawn P334 Concentration effect relationship of infliximab in Crohn’s disease: Results of a cohort study C. Lamblin1 , A. Aubourg1 *, D. Ternant2 , L. Picon1 , T. Lecomte1 , G. Paintaud2 . 1 CHU Tours, Hepatogastroenterology, Tours, France, 2 Universit´ e Fran¸cois Rabelais, CNRS 6239 GICC, Tours, France Background: Infliximab (IFX) has dramatically changed the management of Crohn’s disease. Although it has a proven efficacy in inducing and maintaining remission, loss of response is frequently observed, requiring optimisation. Previous studies were in favor of the measurement of IFX trough concentrations to help therapeutic decisions. The aim of our study was to study concentration effect relationships of IFX in a cohort of Crohn’s disease patients. Methods: All patients with luminal and/or perineal Crohn’s disease with maintenance IFX treatment followed between January 2007 and June 2010 in the Hepatogastroenterology Department of Tours University Hospital were included. Crohn’s Disease Activity Index (CDAI), serum concentration of C-reactive protein (CRP) and IFX trough concentration were measured prospectively in a routine clinical manner. Other demographic and clinical data were collected retrospectively. Because of a large variability in the number of IFX concentrations per patient, statistical analyses were performed using the nearer steady-state concentration for each patient. Concentration effect relationship modeling used Winnonlin® software (Pharsight corp.). Results: Forty-four patients were included. At the time of analysis, 20 patients were in clinical and biological remission and 24 were in relapse. IFX concentrations were significantly higher in patients in remission than in those relapsing, 6.33 mg/L vs 3.39 mg/L (p < 0.02). No significant association was found between IFX concentrations and concomitant immunosuppressive treatment or presence of antibodies to infliximab. The relationship between CRP and IFX concentrations was best described by an Emax inhibition model: estimated EC50, which is the concentration of infliximab leading to a 50% decrease of CRP concentration, was 1.1 mg/L. According to this model, concentration of CRP below 5 mg/L was obtained by IFX concentrations above 5.6 mg/L.