- Email: [email protected]
Efficacy and Safety of Switching from Reference Infliximab to Biosimilar Infliximab in Patients with Inflammatory Bowel Disease: First French Experience
AGA Abstracts
repletion was initiated for deficiencies in vitamin D (n=3) and iron (n=6). From week 0 to 6, mean partial Mayo score improved from 5.8 (SD 1.2) to 1.2 (SD 2.0) (p<0.01) for UC, and mean HBI score improved from 7 (SD 1.5) to 3.6 (SD 2.1) (p<0.01). At baseline, CRP was normal (<10) in 66% (10/15). Among those with labs completed at baseline and week 6, mean CRP (n=11) improved from 8.3 to 7.0 (p=0.46), and mean FC (n=5) improved from 412 (range 80-1078) to 196 (range 0-758) (p=0.36). Among those with follow-up endoscopy at week 11 (n=7), improvements were noted in SES-CD (n=1), Rutgeerts score (n=1), and Mayo endoscopy subscore (n=4). No significant changes in lipid profile observed at week 6. One patient with ileal CD with stricture withdrew due to worsening symptoms. DISCUSSION: Dietary elimination has the potential to improve symptoms and endoscopic inflammation in patients with inflammatory bowel disease. Larger randomized trials are needed to validate these findings.
95% CI 1.5516 to 4.3757, p=0.0003). A proportion of UC significantly higher within the re-induced pts (IFX bridge) required a shift of biological drug compared with the scheduled strategy (p=0.016, Fisher), despite of similar rates of optimization. Infusion reactions needing definitive IFX suspension were more frequent as a tended (p=0.06) in re-induced pts. CONCLUSIONS: similarly to was described for CD pts, in the CU, the scheduled IFX treatment strategy regimen, after a moderate-severe outbreak, seem to be associated with better long-term outcome regarding colectomy requirement, relapses, and need for corticosteroids, compared with a bridge IFX strategy followed by thiopurines.
Sa1945 EFFICACY OF VEDOLIZUMAB IN REDUCING BILIARY INFLAMMATION IN PRIMARY SCLEROSING CHOLANGITIS (PSC) IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE Chung Sang Tse, Edward V. Loftus, Laura H. Raffals, Andrea Gossard, Amy L. Lightner
Sa1943
Introduction: The FDA approved vedolizumab, a gut-selective antibody to α4β7 integrin, in May 2014 for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). Up to 80% of patients with primary sclerosing cholangitis (PSC) have inflammatory bowel disease (IBD), more commonly UC. Unfortunately, there are no effective treatments for PSC to date and a small proportion of patients eventually require liver transplantation. Some preliminary data suggests vedolizumab may be an effective treatment for PSC. We herein sought to determine if vedolizumab therapy was associated with a decrease in liver function tests and magnetic resonance (MR) elastogram scores among IBD patients with PSC. Methods: A retrospective analysis of all IBD patients with PSC who were exposed to vedolizumab for the treatment of UC or CD was conducted. Data collected included patient demographics, IBD and PSC characteristics, vedolizumab treatment and duration, and liver function tests before (within 2 to 3 months) and after (4 to 8 months) initiation of vedolizumab. Radiographic data of the liver was collected from MR elastogram, abdominal magnetic resonance imaging (MRI), and abdominal ultrasounds obtained within 18 months of initiation of vedolizumab. Paired t-test was used to compare liver function tests before and after initiation of vedolizumab. Results: A total of 39 patients (15 female, 39%) were included (Table 1). Median age was 29 years (interquartile range [IQR], 22-39) and median PSC duration was 3.5 years (IQR, 0.25-8.75) at time of vedolizumab initiation. Twenty-four had UC (62%), 12 had CD (31%), and 3 had indeterminate colitis (8%). Median exposure time to vedolizumab was 16 months (IQR, 9-24 months) at the time of data collection. The mean differences in liver function tests following initiation of vedolizumab treatment were AST -12 (95% CI, -60 to 35; p=0.6), ALT -17 (95% CI, -83 to 49; p=0.6), and ALP +89 (95% CI, -37 to 215; p=0.2), total bilirubin -2.1 (95% CI, -4.5 to 0.3; p=0.1), and direct bilirubin -2.9 (95% CI, -7.9 to 2.0; p=0.2) (Table 2). Thirty-three of patients (85%) had liver imaging before and after initiation of vedolizumab; of these, 23 had stable appearance of biliary tree stricture/dilatations (70%), 6 had progression (18%), and 4 had improvement (12%) (one of which had interval ERCP). Four patients had MR elastogram before and after initiation of vedolizumab; of these, the mean change in MR elastography scores was -0.1 kPa (IQR -0.6 to 0.4). Conclusion: While treatment of IBD with vedolizumab in a cohort of PSC patients does not significantly decrease liver enzymes, total bilirubin, direct bilirubin, and elastography score, all have a decreasing trend except for ALP. A larger cohort may be needed to detect a significant difference. At this time, we cannot conclude that vedolizumab is an effective treatment for PSC.
EFFICACY AND SAFETY OF SWITCHING FROM REFERENCE INFLIXIMAB TO BIOSIMILAR INFLIXIMAB IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: FIRST FRENCH EXPERIENCE Pierre-Antoine Soret, Caroline Prieux-Klotz, Jérôme Avouac, Anna Molto, Marie Dior, Bertrand Brieau, Johann Dreanic, Marine Camus, Maximilien Barret, Romain Coriat, Ornella Conort, François Chast, Claire Goulvestre, Claire Le Jeunne, Maxime Dougados, Stephane Nahon, Stanislas Chaussade, Vered Abitbol Introduction Infliximab is widely used for induction and maintenance therapy in inflammatory bowel diseases (IBD). Reference infliximab (Remicade®) was the first anti-TNF available, but its costs are high, placing a strain on healthcare system. CT-P13 is a biosimilar of Remicade® with expected savings of 30%. No data is available in France regarding switching from reference infliximab to CT-P13. We aimed to assess efficacy and safety of switching from reference infliximab to CT-P13 in IBD. Patients and methods From September 30, 2015 to March 30, 2016, a switch to CT-P13 (Inflectra®) and inclusion in a prospective observational study were proposed to all Remicade®-treated patients in our hospital (IBD, rheumatologic diseases, uveitis). Patients had to be on maintenance therapy (>3 Remicade® infusions) with stable treatment. Information was given and non-opposition was required. Data were collected in a anonymous questionnaire at baseline (2 infusions before the switch) and at each biosimilar infusion. Primary endpoint was the rate of patients still treated with Inflectra® after 3 infusions. Secondary endpoints were clinical activity, infliximab trough levels (ITL), anti-infliximab antibodies changes. A closeout visit was performed in July 2016. IBD activity was assessed with Mayo score [ulcerative colitis (UC)] or Harvey-Bradshaw [Crohn's disease (CD)]. ITL and anti-infliximab antibodies were measured before the first and the third CT-P13 infusion. Changes from baseline were analyzed with univariate analysis (Fisher or Mann-Whitney). Results Overall, 268 consecutive patients were enrolled. Among them, 64 had IBD: one patient refused the switch and 63 [33 women, aged 34.5(29-44), 42 CD, 21 UC] were included. At inclusion, duration of Remicade® therapy was 34.8 (1474) months. Three infusions after the switch, 60 (95.2%) were still on Inflectra®. One patient stopped Inflectra® for pregnancy and 2 had IBD relapse: one was switched back to Remicade® and one to adalimumab. In July 2016, 8.4 (7.9-8.9) months after the switch, 2 more patients had stopped CT-P13 for suspected adverse event (purpura) while 55 (87.3%) remained treated with CT-P13. No allergic infusion reaction was reported. Changes from baseline were not significant: Mayo score (p=0.95), Harvey-Bradshaw (p=0.14), infliximab dose (p=0.71) and ITL [baseline (5.9±5µg/mL); third infusion (7.8±6µg/mL) (p=0.09)]. No patient developed anti-infliximab antibodies after the switch. Conclusion This prospective observational study suggests that the switch from reference infliximab to CT-P13 does not change IBD evolution. After 3 infusions, 95.2% patients remained on CT-P13 treatment. No changes in clinical activity, infliximab doses and ITL were observed. No anti-infliximab antibodies appeared.
Sa1944 INFLIXIMAB (IFX) IN MODERATE TO SEVERE ULCERATIVE COLITIS (UC): COMPARISON BETWEEN SCHEDULED TREATMENT STRATEGY AND BRIDGE STRATEGY Alicia M. Sambuelli, Maricel I. Bellicoso, Silvina A. Goncalves, Silvia Negreira, Sergio P. Huernos, Paula Chavero, cecilia carraro, Pablo Tirado, Ana Cabanne, Anibal H. Gil BACKGROUND: UC is a potentially severe disease that carries an increased risk of complications and colectomy. Immunosuppressant and biological therapies are relevant tools for complex patients. The ACCENT study showed that in Crohn‘s disease (CD), scheduled IFX infusions vs. episodic are associated with greater efficacy. In UC, historical difficulties of economic access had conditioned to our IBD center, to use IFX in moderate to severe UC as a bridge to thiopurines in pts 6mp/aza naïve. In UC, the mentioned strategy was insufficiently compared with a regimen of scheduled IFX treatment, that currently we use. AIMS: to compare (retrospectively) in moderate to severe UC the results of induction with IFX (in thiopurine naïve pts.) continuing with 6mp/aza maintenance vs. similar induction followed by scheduled IFX maintenance strategy. MATERIAL AND METHODS: We included a cohort of moderate to severe UC treated with IFX in an IBD center (2006 to 2015) comparing results between IFX bridge followed by thiopurines (re-induction when available for moderate to severe relapse) vs. scheduled IFX (induction 0,2,6 wks and 8 wks' interval infusions maintenance). Optimization (by frequency of intervals) were allowed in both modalities. Comparisons: Kaplan Meier/Log rank test: a) Cumulative prevalence of colectomy, b) survival times relapse free, c) survival times corticosteroid free. RESULTS: We identified 135 UC patients receiving IFX for moderate to severe UC (M 60, F 75, Age (mean±SD) 35.9±13.2, UC duration 5.8±5.9 yrs, Extent: extensive 58.5%, Left-sided 41.5%, Activity: severe 78.5%, moderate 21.5%, mean Mayo score: 10.1±1.8. Primary no responders at week 12 (n 25: 18,5%) were not considered in maintenance comparisons, which were performed in 110 out of the 135 pts. (Follow-up 37.5±24.0 months) Groups: IFX bridge (n=51) and scheduled IFX (n 59), which were not different in extent, and mean age, UC duration, Mayo score. Cumulative prevalence of colectomy was significantly lower in the scheduled strategy (HR: 6.8805, 95% CI 1.7207 to 27.5133, p=0.0349), as well as survival times free of relapse (HR 3.1026, 95% CI 1,8368 to 5.2405, p<0.0001) and free of corticosteroids (HR 2.6057,
AGA Abstracts
S-402
repletion was initiated for deficiencies in vitamin D (n=3) and iron (n=6). From week 0 to 6, mean partial Mayo score improved from 5.8 (SD 1.2) to 1.2 (SD 2.0) (p<0.01) for UC, and mean HBI score improved from 7 (SD 1.5) to 3.6 (SD 2.1) (p<0.01). At baseline, CRP was normal (<10) in 66% (10/15). Among those with labs completed at baseline and week 6, mean CRP (n=11) improved from 8.3 to 7.0 (p=0.46), and mean FC (n=5) improved from 412 (range 80-1078) to 196 (range 0-758) (p=0.36). Among those with follow-up endoscopy at week 11 (n=7), improvements were noted in SES-CD (n=1), Rutgeerts score (n=1), and Mayo endoscopy subscore (n=4). No significant changes in lipid profile observed at week 6. One patient with ileal CD with stricture withdrew due to worsening symptoms. DISCUSSION: Dietary elimination has the potential to improve symptoms and endoscopic inflammation in patients with inflammatory bowel disease. Larger randomized trials are needed to validate these findings.
95% CI 1.5516 to 4.3757, p=0.0003). A proportion of UC significantly higher within the re-induced pts (IFX bridge) required a shift of biological drug compared with the scheduled strategy (p=0.016, Fisher), despite of similar rates of optimization. Infusion reactions needing definitive IFX suspension were more frequent as a tended (p=0.06) in re-induced pts. CONCLUSIONS: similarly to was described for CD pts, in the CU, the scheduled IFX treatment strategy regimen, after a moderate-severe outbreak, seem to be associated with better long-term outcome regarding colectomy requirement, relapses, and need for corticosteroids, compared with a bridge IFX strategy followed by thiopurines.
Sa1945 EFFICACY OF VEDOLIZUMAB IN REDUCING BILIARY INFLAMMATION IN PRIMARY SCLEROSING CHOLANGITIS (PSC) IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE Chung Sang Tse, Edward V. Loftus, Laura H. Raffals, Andrea Gossard, Amy L. Lightner
Sa1943
Introduction: The FDA approved vedolizumab, a gut-selective antibody to α4β7 integrin, in May 2014 for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). Up to 80% of patients with primary sclerosing cholangitis (PSC) have inflammatory bowel disease (IBD), more commonly UC. Unfortunately, there are no effective treatments for PSC to date and a small proportion of patients eventually require liver transplantation. Some preliminary data suggests vedolizumab may be an effective treatment for PSC. We herein sought to determine if vedolizumab therapy was associated with a decrease in liver function tests and magnetic resonance (MR) elastogram scores among IBD patients with PSC. Methods: A retrospective analysis of all IBD patients with PSC who were exposed to vedolizumab for the treatment of UC or CD was conducted. Data collected included patient demographics, IBD and PSC characteristics, vedolizumab treatment and duration, and liver function tests before (within 2 to 3 months) and after (4 to 8 months) initiation of vedolizumab. Radiographic data of the liver was collected from MR elastogram, abdominal magnetic resonance imaging (MRI), and abdominal ultrasounds obtained within 18 months of initiation of vedolizumab. Paired t-test was used to compare liver function tests before and after initiation of vedolizumab. Results: A total of 39 patients (15 female, 39%) were included (Table 1). Median age was 29 years (interquartile range [IQR], 22-39) and median PSC duration was 3.5 years (IQR, 0.25-8.75) at time of vedolizumab initiation. Twenty-four had UC (62%), 12 had CD (31%), and 3 had indeterminate colitis (8%). Median exposure time to vedolizumab was 16 months (IQR, 9-24 months) at the time of data collection. The mean differences in liver function tests following initiation of vedolizumab treatment were AST -12 (95% CI, -60 to 35; p=0.6), ALT -17 (95% CI, -83 to 49; p=0.6), and ALP +89 (95% CI, -37 to 215; p=0.2), total bilirubin -2.1 (95% CI, -4.5 to 0.3; p=0.1), and direct bilirubin -2.9 (95% CI, -7.9 to 2.0; p=0.2) (Table 2). Thirty-three of patients (85%) had liver imaging before and after initiation of vedolizumab; of these, 23 had stable appearance of biliary tree stricture/dilatations (70%), 6 had progression (18%), and 4 had improvement (12%) (one of which had interval ERCP). Four patients had MR elastogram before and after initiation of vedolizumab; of these, the mean change in MR elastography scores was -0.1 kPa (IQR -0.6 to 0.4). Conclusion: While treatment of IBD with vedolizumab in a cohort of PSC patients does not significantly decrease liver enzymes, total bilirubin, direct bilirubin, and elastography score, all have a decreasing trend except for ALP. A larger cohort may be needed to detect a significant difference. At this time, we cannot conclude that vedolizumab is an effective treatment for PSC.
EFFICACY AND SAFETY OF SWITCHING FROM REFERENCE INFLIXIMAB TO BIOSIMILAR INFLIXIMAB IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: FIRST FRENCH EXPERIENCE Pierre-Antoine Soret, Caroline Prieux-Klotz, Jérôme Avouac, Anna Molto, Marie Dior, Bertrand Brieau, Johann Dreanic, Marine Camus, Maximilien Barret, Romain Coriat, Ornella Conort, François Chast, Claire Goulvestre, Claire Le Jeunne, Maxime Dougados, Stephane Nahon, Stanislas Chaussade, Vered Abitbol Introduction Infliximab is widely used for induction and maintenance therapy in inflammatory bowel diseases (IBD). Reference infliximab (Remicade®) was the first anti-TNF available, but its costs are high, placing a strain on healthcare system. CT-P13 is a biosimilar of Remicade® with expected savings of 30%. No data is available in France regarding switching from reference infliximab to CT-P13. We aimed to assess efficacy and safety of switching from reference infliximab to CT-P13 in IBD. Patients and methods From September 30, 2015 to March 30, 2016, a switch to CT-P13 (Inflectra®) and inclusion in a prospective observational study were proposed to all Remicade®-treated patients in our hospital (IBD, rheumatologic diseases, uveitis). Patients had to be on maintenance therapy (>3 Remicade® infusions) with stable treatment. Information was given and non-opposition was required. Data were collected in a anonymous questionnaire at baseline (2 infusions before the switch) and at each biosimilar infusion. Primary endpoint was the rate of patients still treated with Inflectra® after 3 infusions. Secondary endpoints were clinical activity, infliximab trough levels (ITL), anti-infliximab antibodies changes. A closeout visit was performed in July 2016. IBD activity was assessed with Mayo score [ulcerative colitis (UC)] or Harvey-Bradshaw [Crohn's disease (CD)]. ITL and anti-infliximab antibodies were measured before the first and the third CT-P13 infusion. Changes from baseline were analyzed with univariate analysis (Fisher or Mann-Whitney). Results Overall, 268 consecutive patients were enrolled. Among them, 64 had IBD: one patient refused the switch and 63 [33 women, aged 34.5(29-44), 42 CD, 21 UC] were included. At inclusion, duration of Remicade® therapy was 34.8 (1474) months. Three infusions after the switch, 60 (95.2%) were still on Inflectra®. One patient stopped Inflectra® for pregnancy and 2 had IBD relapse: one was switched back to Remicade® and one to adalimumab. In July 2016, 8.4 (7.9-8.9) months after the switch, 2 more patients had stopped CT-P13 for suspected adverse event (purpura) while 55 (87.3%) remained treated with CT-P13. No allergic infusion reaction was reported. Changes from baseline were not significant: Mayo score (p=0.95), Harvey-Bradshaw (p=0.14), infliximab dose (p=0.71) and ITL [baseline (5.9±5µg/mL); third infusion (7.8±6µg/mL) (p=0.09)]. No patient developed anti-infliximab antibodies after the switch. Conclusion This prospective observational study suggests that the switch from reference infliximab to CT-P13 does not change IBD evolution. After 3 infusions, 95.2% patients remained on CT-P13 treatment. No changes in clinical activity, infliximab doses and ITL were observed. No anti-infliximab antibodies appeared.
Sa1944 INFLIXIMAB (IFX) IN MODERATE TO SEVERE ULCERATIVE COLITIS (UC): COMPARISON BETWEEN SCHEDULED TREATMENT STRATEGY AND BRIDGE STRATEGY Alicia M. Sambuelli, Maricel I. Bellicoso, Silvina A. Goncalves, Silvia Negreira, Sergio P. Huernos, Paula Chavero, cecilia carraro, Pablo Tirado, Ana Cabanne, Anibal H. Gil BACKGROUND: UC is a potentially severe disease that carries an increased risk of complications and colectomy. Immunosuppressant and biological therapies are relevant tools for complex patients. The ACCENT study showed that in Crohn‘s disease (CD), scheduled IFX infusions vs. episodic are associated with greater efficacy. In UC, historical difficulties of economic access had conditioned to our IBD center, to use IFX in moderate to severe UC as a bridge to thiopurines in pts 6mp/aza naïve. In UC, the mentioned strategy was insufficiently compared with a regimen of scheduled IFX treatment, that currently we use. AIMS: to compare (retrospectively) in moderate to severe UC the results of induction with IFX (in thiopurine naïve pts.) continuing with 6mp/aza maintenance vs. similar induction followed by scheduled IFX maintenance strategy. MATERIAL AND METHODS: We included a cohort of moderate to severe UC treated with IFX in an IBD center (2006 to 2015) comparing results between IFX bridge followed by thiopurines (re-induction when available for moderate to severe relapse) vs. scheduled IFX (induction 0,2,6 wks and 8 wks' interval infusions maintenance). Optimization (by frequency of intervals) were allowed in both modalities. Comparisons: Kaplan Meier/Log rank test: a) Cumulative prevalence of colectomy, b) survival times relapse free, c) survival times corticosteroid free. RESULTS: We identified 135 UC patients receiving IFX for moderate to severe UC (M 60, F 75, Age (mean±SD) 35.9±13.2, UC duration 5.8±5.9 yrs, Extent: extensive 58.5%, Left-sided 41.5%, Activity: severe 78.5%, moderate 21.5%, mean Mayo score: 10.1±1.8. Primary no responders at week 12 (n 25: 18,5%) were not considered in maintenance comparisons, which were performed in 110 out of the 135 pts. (Follow-up 37.5±24.0 months) Groups: IFX bridge (n=51) and scheduled IFX (n 59), which were not different in extent, and mean age, UC duration, Mayo score. Cumulative prevalence of colectomy was significantly lower in the scheduled strategy (HR: 6.8805, 95% CI 1.7207 to 27.5133, p=0.0349), as well as survival times free of relapse (HR 3.1026, 95% CI 1,8368 to 5.2405, p<0.0001) and free of corticosteroids (HR 2.6057,
AGA Abstracts
S-402