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P498 Efficacy of anti TNF-treatment for fistulizing Crohn's disease
Clinical: Therapy & observation
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continued to receive PBO; week 6 PBO nonresponders were the comparators in this analysis. At weeks 10 and 14 (prespecified) and week 52 (post hoc), proportions of week 6 nonresponders in clinical remission (CDAI score 150 points) and of those with a CDAI-100 response (100-point decrease in CDAI score from baseline) were assessed, as were week 52 end points for those with a delayed response at week 10 or 14. Results: Mean CD durations (VDZ, 9.2 years; PBO, 8.2 years) and CDAI scores (VDZ, 323.4; PBO, 324.6) were similar for the VDZ (cohorts 1 and 2; n = 967) and PBO (cohort 1; n = 148) groups at baseline; tumor necrosis factor antagonists had failed in 59% of VDZ and 47% of PBO patients. Proportions of week 6 nonresponders in clinical remission or with a CDAI-100 response at week 10, 14, or 52 were generally numerically higher with VDZ than with PBO (Table). For both end points, the between-treatment group differences generally increased over time and were more pronounced for CDAI-100 response than for remission. Proportions of week 6 nonresponders with remission (41.3%) or a CDAI-100 response (54.5%) at week 52 were higher in week 14 delayed VDZ responders (n = 121) than proportions (33.3% and 43.8%, respectively) in week 10 delayed VDZ responders (n = 96). Among PBO-treated patients, proportions of patients with remission or a CDAI-100 response were 16.7% and 25%, respectively, at week 52 in week 14 responders (n = 12), while the proportions were 16.7% and 16.7%, respectively in week 10 responders (n = 6); however, subgroup sizes were small. End points in Wk 6 Nonresponders a
VDZ combined (Induction cohorts 1 and 2) PBO (Induction cohort 1) n = 351 n = 69 Wk 10 b Wk 14 b Wk 52 c Wk 10 b Wk 14 b Wk 52 c
Clinical remission 95% CI CDAI-100 response 95% CI
6.8 (4.2, 9.5) 16.0 (12.1, 19.8)
10.5 (7.3, 13.8) 21.7 (17.3, 26.0)
18.8 (14.7, 22.9) 25.4 (20.8, 29.9)
4.3 (0, 9.2) 7.2 (3.0, 17.3)
10.1 (3.0, 17.3) 11.6 (4.0, 19.1)
7.2 (1.1, 13.4) 7.2 (1.1, 13.4)
a Data are % of patients. PBO, placebo; VDZ, vedolizumab. b Prespecified analysis. c Post hoc analysis.
Conclusions: In week 6 induction nonresponders with CD, continued VDZ led to additional effects on clinical remission and CDAI-100 response rates at weeks 10, 14, and 52. P498 Efficacy of anti TNF-treatment for fistulizing Crohn’s disease J. Maljaars1 *, I. Molendijk1 , C. Baeten2 , R. Veenendaal1 , A. Van der Meulen1 . 1 Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, Netherlands, 2 Leiden University Medical Centre, Surgery, Leiden, Netherlands Background: Anti-TNF is the best currently available medical treatment modality for treating perianal fistulizing Crohn’s disease (CD). However, whether the efficacy is comparable between adalimumab (ADA) and infliximab (IFX) has never been studied. Furthermore, little is known about the long-term outcomes of anti-TNF in these patients. Methods: In this retrospective cohort study, we identified all patients with CD who used anti-TNF in 2011. Demographics and received anti-TNF treatment were noted and response (sustained reduction in fistula effusion or remission) and remission (closure of fistula at physical examination) were determined. Survival analysis was performed by Kaplan Meier and Log-Rank test, covariate analysis with a Cox regression model. Results: From 288 patients with CD who are current or previous users of anti-TNF, 103 patients were identified with fistulizing CD. In 58 patients, anti-TNF treatment was started during a period of active fistulizing disease. These patients had a median age of 26.5 yrs [interquartile range (IQR) 21.2 35] and 57% (33/58) were female. The majority, 87%, had a perianal fistula. IFX was started in 81% (47/58) patients and ADA was started in 19% (11/58) patients The overall response to treatment was
65% (38/58): 64% (30/47) of the patients treated with IFX and 55% (6/11) of the patients treated with ADA (p = 0.54). Use of immune-modulator co-medication did not influence the response rate (p = 0.62), nor did age, sex or duration of fistula existence prior to start anti-TNF. In 16 out of 19 patients (84%) who did not respond, anti-TNF treatment was switched (14 times IFX to ADA, twice ADA to IFX). After this switch, 38% (6/16) of the patients responded to antiTNF treatment. This was significantly lower when compared to the success rate of the first treatment (p < 0.001). In total, 44 (38 plus 6) patients were in remission due to antiTNF. These patients were followed for a median of 45 months (IQR 19.25 84.75). In this period, 25% (11/44) of the patients relapsed. Risk of relapse was not affected by patient age or sex, smoking or type of anti-TNF used for induction of remission. There was a trend towards a greater risk for relapse in patients in whom anti-TNF was switched during remission-induction (RR 1.56, p = 0.054) in the univariate analysis; in multivariate analysis, no effect was present. Conclusions: Response to anti-TNF treatment in fistulizing Crohn’s disease is 65% and is not significantly different between ADA and IFX. When the first anti TNF is not successful, an additional 38% of patients respond after switch of therapy. After long-term follow up, 25% of the patients will experience a relapse of fistulizing disease. P499 Efficacy of adalimumab for induction and maintenance of remission in intestinal Beh¸ cet’s disease A. Yamada *, Y. Suzuki, T. Sasaki, M. Katsumata, M. Miyamura, K. Hirayama, N. Arai, H. Kikuchi, R. Iwasa, R. Furukawa, K. Sono, A. Osamura, K. Nakamura, H. Aoki, Y. Yoshimatsu, Y. Tsuda, K. Takeuchi, N. Takada. Toho University, Sakura Medical Centre, Division of Gastroenterology, Department of Internal Medicine, Sakura, Japan Background: Beh¸ cet’s disease (BD) is chronic inflammatory disease affecting multiple organ systems, such as the skin, joints, blood vessels, central nervous system, and gastrointestinal tract. Intestinal BD is characterized by intestinal inflammation with round and oval ulcers associated with gastrointestinal symptoms. Gastrointestinal lesions of BD are often refractory to medical therapy. Although several cases have been reported that anti-TNF therapy, mainly infliximab, is effective for induction of remission, and maintaining remission, but a few reported about adalimumab (ADA). We reported about the efficacy of ADA for remission and maintenance therapy in intestinal BD patients. Methods: This study was single center retrospective analysis. From August 2011 to October 2013, Seven cases (3 female and 4 male) with active intestinal BD were treated with ADA as an induction remission therapy, there after clinical corse were monitored, had colonoscopies performed up to 8 weeks after induction therapy. All paitients were steroid-dependent or refractory. The remission induction rate, the maintenance rate and the endoscopic findings were evaluated. Results: The remission induction rate 8 weeks after the treatment with ADA was 42.8% (3/7), and all of these patients maintained remission with scheduled treatments of ADA. The rate of improvement of endoscopic findings was 42.8% (3/7) after 8 weeks. Overall ADA achieved clinical improvement and keep remission and response in 5 of the 7 patients. Conclusions: ADA appears to offer an option for active intestinal BD to induce and maintain remission.
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continued to receive PBO; week 6 PBO nonresponders were the comparators in this analysis. At weeks 10 and 14 (prespecified) and week 52 (post hoc), proportions of week 6 nonresponders in clinical remission (CDAI score 150 points) and of those with a CDAI-100 response (100-point decrease in CDAI score from baseline) were assessed, as were week 52 end points for those with a delayed response at week 10 or 14. Results: Mean CD durations (VDZ, 9.2 years; PBO, 8.2 years) and CDAI scores (VDZ, 323.4; PBO, 324.6) were similar for the VDZ (cohorts 1 and 2; n = 967) and PBO (cohort 1; n = 148) groups at baseline; tumor necrosis factor antagonists had failed in 59% of VDZ and 47% of PBO patients. Proportions of week 6 nonresponders in clinical remission or with a CDAI-100 response at week 10, 14, or 52 were generally numerically higher with VDZ than with PBO (Table). For both end points, the between-treatment group differences generally increased over time and were more pronounced for CDAI-100 response than for remission. Proportions of week 6 nonresponders with remission (41.3%) or a CDAI-100 response (54.5%) at week 52 were higher in week 14 delayed VDZ responders (n = 121) than proportions (33.3% and 43.8%, respectively) in week 10 delayed VDZ responders (n = 96). Among PBO-treated patients, proportions of patients with remission or a CDAI-100 response were 16.7% and 25%, respectively, at week 52 in week 14 responders (n = 12), while the proportions were 16.7% and 16.7%, respectively in week 10 responders (n = 6); however, subgroup sizes were small. End points in Wk 6 Nonresponders a
VDZ combined (Induction cohorts 1 and 2) PBO (Induction cohort 1) n = 351 n = 69 Wk 10 b Wk 14 b Wk 52 c Wk 10 b Wk 14 b Wk 52 c
Clinical remission 95% CI CDAI-100 response 95% CI
6.8 (4.2, 9.5) 16.0 (12.1, 19.8)
10.5 (7.3, 13.8) 21.7 (17.3, 26.0)
18.8 (14.7, 22.9) 25.4 (20.8, 29.9)
4.3 (0, 9.2) 7.2 (3.0, 17.3)
10.1 (3.0, 17.3) 11.6 (4.0, 19.1)
7.2 (1.1, 13.4) 7.2 (1.1, 13.4)
a Data are % of patients. PBO, placebo; VDZ, vedolizumab. b Prespecified analysis. c Post hoc analysis.
Conclusions: In week 6 induction nonresponders with CD, continued VDZ led to additional effects on clinical remission and CDAI-100 response rates at weeks 10, 14, and 52. P498 Efficacy of anti TNF-treatment for fistulizing Crohn’s disease J. Maljaars1 *, I. Molendijk1 , C. Baeten2 , R. Veenendaal1 , A. Van der Meulen1 . 1 Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, Netherlands, 2 Leiden University Medical Centre, Surgery, Leiden, Netherlands Background: Anti-TNF is the best currently available medical treatment modality for treating perianal fistulizing Crohn’s disease (CD). However, whether the efficacy is comparable between adalimumab (ADA) and infliximab (IFX) has never been studied. Furthermore, little is known about the long-term outcomes of anti-TNF in these patients. Methods: In this retrospective cohort study, we identified all patients with CD who used anti-TNF in 2011. Demographics and received anti-TNF treatment were noted and response (sustained reduction in fistula effusion or remission) and remission (closure of fistula at physical examination) were determined. Survival analysis was performed by Kaplan Meier and Log-Rank test, covariate analysis with a Cox regression model. Results: From 288 patients with CD who are current or previous users of anti-TNF, 103 patients were identified with fistulizing CD. In 58 patients, anti-TNF treatment was started during a period of active fistulizing disease. These patients had a median age of 26.5 yrs [interquartile range (IQR) 21.2 35] and 57% (33/58) were female. The majority, 87%, had a perianal fistula. IFX was started in 81% (47/58) patients and ADA was started in 19% (11/58) patients The overall response to treatment was
65% (38/58): 64% (30/47) of the patients treated with IFX and 55% (6/11) of the patients treated with ADA (p = 0.54). Use of immune-modulator co-medication did not influence the response rate (p = 0.62), nor did age, sex or duration of fistula existence prior to start anti-TNF. In 16 out of 19 patients (84%) who did not respond, anti-TNF treatment was switched (14 times IFX to ADA, twice ADA to IFX). After this switch, 38% (6/16) of the patients responded to antiTNF treatment. This was significantly lower when compared to the success rate of the first treatment (p < 0.001). In total, 44 (38 plus 6) patients were in remission due to antiTNF. These patients were followed for a median of 45 months (IQR 19.25 84.75). In this period, 25% (11/44) of the patients relapsed. Risk of relapse was not affected by patient age or sex, smoking or type of anti-TNF used for induction of remission. There was a trend towards a greater risk for relapse in patients in whom anti-TNF was switched during remission-induction (RR 1.56, p = 0.054) in the univariate analysis; in multivariate analysis, no effect was present. Conclusions: Response to anti-TNF treatment in fistulizing Crohn’s disease is 65% and is not significantly different between ADA and IFX. When the first anti TNF is not successful, an additional 38% of patients respond after switch of therapy. After long-term follow up, 25% of the patients will experience a relapse of fistulizing disease. P499 Efficacy of adalimumab for induction and maintenance of remission in intestinal Beh¸ cet’s disease A. Yamada *, Y. Suzuki, T. Sasaki, M. Katsumata, M. Miyamura, K. Hirayama, N. Arai, H. Kikuchi, R. Iwasa, R. Furukawa, K. Sono, A. Osamura, K. Nakamura, H. Aoki, Y. Yoshimatsu, Y. Tsuda, K. Takeuchi, N. Takada. Toho University, Sakura Medical Centre, Division of Gastroenterology, Department of Internal Medicine, Sakura, Japan Background: Beh¸ cet’s disease (BD) is chronic inflammatory disease affecting multiple organ systems, such as the skin, joints, blood vessels, central nervous system, and gastrointestinal tract. Intestinal BD is characterized by intestinal inflammation with round and oval ulcers associated with gastrointestinal symptoms. Gastrointestinal lesions of BD are often refractory to medical therapy. Although several cases have been reported that anti-TNF therapy, mainly infliximab, is effective for induction of remission, and maintaining remission, but a few reported about adalimumab (ADA). We reported about the efficacy of ADA for remission and maintenance therapy in intestinal BD patients. Methods: This study was single center retrospective analysis. From August 2011 to October 2013, Seven cases (3 female and 4 male) with active intestinal BD were treated with ADA as an induction remission therapy, there after clinical corse were monitored, had colonoscopies performed up to 8 weeks after induction therapy. All paitients were steroid-dependent or refractory. The remission induction rate, the maintenance rate and the endoscopic findings were evaluated. Results: The remission induction rate 8 weeks after the treatment with ADA was 42.8% (3/7), and all of these patients maintained remission with scheduled treatments of ADA. The rate of improvement of endoscopic findings was 42.8% (3/7) after 8 weeks. Overall ADA achieved clinical improvement and keep remission and response in 5 of the 7 patients. Conclusions: ADA appears to offer an option for active intestinal BD to induce and maintain remission.