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P344 Short and medium term efficacy of adalimumab in ulcerative colitis – a multicentre, prospective observational study
S208 are particularly at risk for therapy failure. We determined the predictive value of this pharmacological phenomenon in IBD patients. Methods: Clinical effectiveness and tolerability of regular weight-based thiopurine therapy were determined in all IBD patients displaying a skewed metabolism [ratio 6-MMPR/ 6-thioguaninenucleotide (6-TGN) >20]. All samples were routinely assessed between 2008 2012, being part of standard clinical follow-up after initiation of conventional thiopurines. Results: Fourty-one (84%) out of 49 included IBD patients discontinued thiopurines (55% female, 53% with Crohn’s disease and 47% with ulcerative colitis) with a median duration of 14 weeks (IQR 10 29). The majority of patients discontinued thiopurines due to adverse events (55%) or refractoriness (12%). The most commonly observed adverse event was thiopurine induced hepatotoxicity (18 patients, 37%). Median 6-TGN level was 159 pmol/10e8RBC (IQR 113 218 pmol/10e8RBC), median 6-MMPR level was 11020 pmol/10e8RBC (IQR 7210 20340 pmol/10e8RBC) and the median 6-MMPR/6-TGN ratio was 72 (IQR 43 114). Thiopurine therapy failure was associated with a ratio above 50 (p < 0.03). Hepatotoxicity occurred more frequent in patients with an extreme skewed metabolism (6-MMPR/6-TGN ratio >100) (p < 0.01). Conclusions: This study demonstrates that a skewed metabolism is a risk factor for early thiopurine failure in IBD patients. These observations implicate that routine thiopurine metabolite measurements can be used as a prognostic tool to identify those patients with an aberrant metabolism in an early stage, possibly benefitting from therapy adjustments. P344 Short and medium term efficacy of adalimumab in ulcerative colitis a multicentre, prospective observational study Z. Szepes1 *, A. B´ alint1 , M. Sz¨ ucs2 , F. Nagy1 , K. Farkas1 , ´ . Csontos5 , R. Bor1 , L. Lakner3 , K. Palatka4 , P. Miheller5 , A 6 7 8 ´ 9 ath , I. R´ acz , A. Vincze , P.L. Lakatos10 , G. Hegede , G. Horv´ P.A. Golovics10 , Z. G´ abor7 , M. Juh´ asz5 , F. Zsigmond11 , 1 1 1 T. Wittmann , T. Moln´ ar . University of Szeged, First Department of Medicine, Szeged, Hungary, 2 University of Szeged, Department of Medical Physics and Informatics, Szeged, Hungary, 3 Teaching Hospital Markusovszky, Department of Gastroenterology, Szombathely, Hungary, 4 University of Debrecen, 2nd Department of Medicine, Debrecen, Hungary, 5 Semmelweis University, 2nd Department of Medicine, Budapest, Hungary, 6 S´ andor P´ eterfy Hospital, First Department of Medicine, Budapest, Hungary, 7 Semmelweis Health Center, Department of Gastroenterology, Miskolc, Hungary, 8 Petz Alad´ ar Hospital, First Department of Medicine, Gy¨ or, Hungary, 9 University of P´ ecs, First Department of Medicine, P´ ecs, Hungary, 10 Semmelweis University, First Department of Medicine, Budapest, Hungary, 11 National Medical Center, Department of Internal Medicine, Budapest, Hungary Background: Adalimumab is a relatively new therapeutic option in ulcerative colitis (UC). After the ULTRA trials only a few data have been published from the real clinical practice. The aim of this study was to prospectively follow the disease course in adalimumab-treated UC patients in Hungary. Primary endpoints were the remission and response rates at week 12 and 30; while secondary endpoints were the changes of C-reactive protein (CRP) levels and the clinical symptoms during the therapy. Methods: 56 patients who was treated with adalimumab at 10 tertiary Hungarian IBD centres were prospectively enrolled from May 2013 [male/female: 32/24; mean age: 41.9 years (in range: 21 68 years)]. 69.6% of the patients previously received infliximab therapy. Switch to adalimumab in these patients was due to loss of response or intolerance. Clinical data, partial Mayo (pMayo) score and CRP levels were collected at the
Poster presentations beginning of adalimumab therapy, at week 12 and at week 30. Colonoscopy was performed before drug administration. Endoscopic Mayo subscore was used to assess the mucosal activity. Clinical remission was defined as less than or equal to 2 points in pMayo score; response to adalimumab was specified as decreasing 3 or more points. Results: Adalimumab induction was administered at doses of 160 mg and 80 mg at week 0 and week 2. The mean value of Mayo score at the beginning of adalimumab therapy was 9.7 points. The mean values of pMayo subscores and CRP were 6.7 points, 14.2 mg/l at week 12, and 2.3 points, 7.2 mg/l at week 30, respectively. CRP levels and pMayo subscores decreased significantly at week 12 (p = 0.004, p < 0.001), while at week 30 only the decrease of pMayo subscore remained significant (p < 0.001). Remission, response and non-response rates were 23.2%, 75%, and 23.2% at week 12 and 54.5%, 81.8% and 18.2% at week 30. However, no significant difference was detected in the remission, response and non-response rates neither between week 12 and week 30 (p = 0.264) nor between patients previously treated with biologicals or naive to them. Adalimumab therapy needed to be discontinued in 6 subjects. Conclusions: Our results suggest that adalimumab is an effective drug for the induction of remission and for the maintenance therapy of UC. P345 Short- and long-term efficacy of granulocytapheresis in patients with active steroid-dependent ulcerative colitis refractory or intolerant to thiopurines. A retrospective single-centre study F.J. Fernandez-Perez *, A. Moreno *, F.J. Fernandez-Cano, F. Rodriguez Gonzalez, M.A. Romero Ordo˜ nez, M. Gonzalez Barcenas. Hospital Costa del Sol, Gastroenterology, Marbella, Spain Background: Valoration of clinical response at 12 and 52 weeks in patients with active steroid-dependent ulcerative colitis (UC) refractory or intolerant to thiopurines using granulocytapheresis (GCAP) in induction or induction plus maintenance schedules. Need for Colectomy, anti-TNF use and ability to withdraw steroids were also valorated at 12 and 52 weeks after initiation of GCAF. Methods: Retrospective, single-centre series of 27 UC patients treated with GCAP from 2004 to 2011. GCAP (Adacolumn® ) was performed by peripheral vein access with induction (5 sessions in 5 weeks, group A) or induction plus maintenance schedule (5 sessions in 5 weeks plus a monthly session, group B). Statistical analysis was carried out by Fisher’s exact test using SPSS-20. Results: We reviewed 27 patients, mean age 38 years-old (15 81). UC extension included: E1 4 patients, E2 8 patients and E3 15 patients. At the begining of GCAP, 19/27 patients were on oral sistemic corticosteroids while 8/27 in oral topically-acting corticosteroids.. In 14 patients (52%) GCAP consisted in induction plus maintenance sessions. At 12 weeks response was achieved in 48% of patients, for 30% at 52 weeks. When comparing response rate at 12 and 52 weeks in groups A and B, 11% and 7.4% of patients in group A and 29.6% and 22.2% were in clinical response or remission at 12 and 52 weeks respectively. At 52 weeks Anti-TNF was used in17/27 patients (62.9%) and 6/27 required colectomy (22.2%), while 8/27 (29.6%) patients could avoid anti-TNF or colectomy and were on clinical response or remission. Of these, 6 out of 8 were free of steroids. Conclusions: At 52 weeks almost one third of steroiddependent and thiopurine-refractory or intolerant UC patients treated with GCAP achieved remission/response.and avoided anti-TNF treatment or colectomy. Response rates were more consistent in patients treated with induction and maintenance GCAP.
Poster presentations beginning of adalimumab therapy, at week 12 and at week 30. Colonoscopy was performed before drug administration. Endoscopic Mayo subscore was used to assess the mucosal activity. Clinical remission was defined as less than or equal to 2 points in pMayo score; response to adalimumab was specified as decreasing 3 or more points. Results: Adalimumab induction was administered at doses of 160 mg and 80 mg at week 0 and week 2. The mean value of Mayo score at the beginning of adalimumab therapy was 9.7 points. The mean values of pMayo subscores and CRP were 6.7 points, 14.2 mg/l at week 12, and 2.3 points, 7.2 mg/l at week 30, respectively. CRP levels and pMayo subscores decreased significantly at week 12 (p = 0.004, p < 0.001), while at week 30 only the decrease of pMayo subscore remained significant (p < 0.001). Remission, response and non-response rates were 23.2%, 75%, and 23.2% at week 12 and 54.5%, 81.8% and 18.2% at week 30. However, no significant difference was detected in the remission, response and non-response rates neither between week 12 and week 30 (p = 0.264) nor between patients previously treated with biologicals or naive to them. Adalimumab therapy needed to be discontinued in 6 subjects. Conclusions: Our results suggest that adalimumab is an effective drug for the induction of remission and for the maintenance therapy of UC. P345 Short- and long-term efficacy of granulocytapheresis in patients with active steroid-dependent ulcerative colitis refractory or intolerant to thiopurines. A retrospective single-centre study F.J. Fernandez-Perez *, A. Moreno *, F.J. Fernandez-Cano, F. Rodriguez Gonzalez, M.A. Romero Ordo˜ nez, M. Gonzalez Barcenas. Hospital Costa del Sol, Gastroenterology, Marbella, Spain Background: Valoration of clinical response at 12 and 52 weeks in patients with active steroid-dependent ulcerative colitis (UC) refractory or intolerant to thiopurines using granulocytapheresis (GCAP) in induction or induction plus maintenance schedules. Need for Colectomy, anti-TNF use and ability to withdraw steroids were also valorated at 12 and 52 weeks after initiation of GCAF. Methods: Retrospective, single-centre series of 27 UC patients treated with GCAP from 2004 to 2011. GCAP (Adacolumn® ) was performed by peripheral vein access with induction (5 sessions in 5 weeks, group A) or induction plus maintenance schedule (5 sessions in 5 weeks plus a monthly session, group B). Statistical analysis was carried out by Fisher’s exact test using SPSS-20. Results: We reviewed 27 patients, mean age 38 years-old (15 81). UC extension included: E1 4 patients, E2 8 patients and E3 15 patients. At the begining of GCAP, 19/27 patients were on oral sistemic corticosteroids while 8/27 in oral topically-acting corticosteroids.. In 14 patients (52%) GCAP consisted in induction plus maintenance sessions. At 12 weeks response was achieved in 48% of patients, for 30% at 52 weeks. When comparing response rate at 12 and 52 weeks in groups A and B, 11% and 7.4% of patients in group A and 29.6% and 22.2% were in clinical response or remission at 12 and 52 weeks respectively. At 52 weeks Anti-TNF was used in17/27 patients (62.9%) and 6/27 required colectomy (22.2%), while 8/27 (29.6%) patients could avoid anti-TNF or colectomy and were on clinical response or remission. Of these, 6 out of 8 were free of steroids. Conclusions: At 52 weeks almost one third of steroiddependent and thiopurine-refractory or intolerant UC patients treated with GCAP achieved remission/response.and avoided anti-TNF treatment or colectomy. Response rates were more consistent in patients treated with induction and maintenance GCAP.