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954 Infliximab Maintenance Beyond One Year Prevents Postoperative Crohn's Disease Recurrence: Long-Term Follow-up From the Randomized Controlled Pilot Study
surgery for a CD complication. Results: All 24 pts from the initial randomized controlled postop prevention trial were followed prospectively for at least 4 yrs. (Table) One of the placebo patients required another surgery within the first year of the initial study and then received postop IFX. For purposes of long-term follow-up analysis, this pt is included in the postop IFX group. Of the 12 pts who received postop IFX for 1 yr, 5 stopped IFX - all had endoscopic recurrence and 4 had another surgery. Of the 7 who continued IFX, none required surgery and all maintained the same endoscopic score; 2 of these pts (i0) ultimately stopped IFX and had endoscopic recurrence (i3). Of the 12 pts who received placebo for 1 yr after surgery, 2 did not start IFX and both required another surgery. Of the 10 who started IFX 1 yr postop, 3 (i3,i4,i4) had no improvement and required another surgery, whereas 7 maintained or improved (6 of these pts ultimately stopped IFX: all had endoscopic recurrence and 1 had another surgery). No other IBD meds were added during the followup period. When considering each colonoscopy and surgery as a separate event, there were 57 total events; 27 colonoscopies and 3 surgeries in pts ON IFX, and 18 colonoscopies and 9 surgeries in pts OFF IFX. The endoscopic and surgical recurrence rates were significantly higher in pts OFF IFX compared with ON IFX (40% v 11%; p , .05 and 75% v 25%; p,.05, respectively). Conclusions: Postoperative IFX prevents CD recurrence and need for additional surgery. Initiation of IFX in response to endoscopic recurrence is effective at inducing remission and avoiding additional surgery in pts with mild to moderate endoscopic recurrence (i1 or i2), but not severe recurrence (i4). Stopping postop IFX in high risk CD pts in remission results in endoscopic recurrence and additional surgery. Long-term Follow-up of Postoperative Crohn's Disease Patients
953 Prolonged Exposure to Prednisone Is Decreasing in Children With Inflammatory Bowel Disease (IBD) During the Last Decade Julia Sorbara, David R. Mack, Trudy Lerer, Anthony R. Otley, Neal S. Leleiko, Anne M. Griffiths, Jonathan Evans, David J. Keljo, Marian D. Pfefferkorn, Joel R. Rosh, James Rick, Athos Bousvaros, Maria Oliva-Hemker, Jose Cabrera, Ryan Carvalho, Shehzad A. Saeed, Andrew B. Grossman, Michael Kappelman, Meredith C. Hitch, William A. Faubion, Marc Schaefer, Boris Sudel, James Markowitz, Jeffrey S. Hyams Background: Prednisone (Pred), a mainstay for therapy in children with IBD, may be associated with significant side effects. Increasing use of immunomodulators (IM) and antiTNFα agents over the last decade may have decreased utilization of Pred. We evaluated whether there has been a change in utilization over the last 10 years. Aim: To examine patterns of Pred use in pediatric IBD. Methods: Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. This is an observational cohort study enrolling patients ,16 years of age. Data are gathered at time of diagnosis (dx), 30 days later and quarterly thereafter. Therapies are by physician dictate, not protocol. Pred use was compared for patients enrolled between 2002-2005 (T1) and 2006-2010 (T2). Exposure was measured as number of quarters (Q) with any Pred use in the first year after dx. Results: A total of 1344 children with a final diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) with at least one year follow-up were enrolled (57% male, age at dx 11.8±3.1 years, Physician Global Assessment of disease severity (PGA) 29% mild, 52% moderate, 19% severe). Included were 654 (474 CD; 180 UC) subjects diagnosed during T1 and 690 (504 CD; 186 UC) during T2. The 2 groups were similar for gender (males: 58% vs. 56%), age of dx (CD: 11.7 vs. 12.1 years; UC: 10.9 vs. 13.1 years), PGA (31% vs. 27%; 52% vs. 53%; 17% vs. 20% for mild; moderate; severe disease; respectively). In the first 3 months following dx (Q1), Pred had been administered to a similar number of children with CD (73% vs. 70%) and with UC (71% vs. 71%) during the two time periods. By the end of the first year (Q4), a similar number of children with CD (78% vs. 75%) and UC (79% vs. 78%) had received Pred during both time periods. By Q4 however, patients in T1 had more quarters of Pred exposure than those from T2 (P,0.02). In addition, more patients from T1 compared to T2 received Pred in all 4 quarters of the first year (All IBD: 13% vs. 6%, P ,0.001; CD 11% vs. 5%, P ,0.001; UC: 20% vs. 10%, P,0.02). However, patients not receiving Pred in Q1 showed no difference in subsequent exposure between time periods (16% in both T1 and T2 received Pred during Q2 to Q4). As shown in the Table, among patients who received Pred in Q1 there were fewer UC patients receiving IM in the first year (P ,0.02) and increased use of biologic therapy by the end of Q1 (P,0.02) and by the end of Q4 (P ,0.01) in T2 compared to T1. Use of IM and biologic agents for CD patients receiving Pred in Q1 are consistent in direction but not statistically different (see Table) for the two time periods. Conclusion: Although any time Pred exposure is similar in the first 3 months of dx over the last 10 years, prolonged exposure has dramatically decreased in the latter time period. Use of Concomitant Therapies in Patients who Received Pred in First 3 Months Following Dx
Postoperative CD course per patient. Year 0 to 1 is the first postop year as part of the orginal RCT. Indication for initial and subsequent surgeries: B2=Stricture, B3=Fistula. IFX status (ON or OFF), endoscopic scores (i0-i4) and surgery recorded for first 5 yrs after initial (year 0) surgery. 955 Effect of Allopurinol on Clinical, Endoscopic and Metabolic Outcomes of Thiopurine Therapy in IBD Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G. Seidman
Q1=in the first 3 month of Dx; Q4=in the first year since Dx; IM=immunomodulators *P,0.01; **P,0.02 comparing 2--2-2005 vs. 2006-2010
Thiopurines are among the most commonly used maintenance medications for IBD. However, excessive methylation via the TPMT enzymatic route causes therapeutic failure, due to excessive production of 6-methyl-mercaptopurine (6MMP) and sub-therapeutic 6-thioguanine (6TGN) levels. Allopurinol has been shown to favourably alter 6MP metabolism, reducing 6MMP while favoring 6-TGN production. Our aim was to evaluate the clinical, metabolic and endoscopic impact of allopurinol in thiopurine non-responding patients. Method: Retrospective review of 50 consecutive cases treated with allopurinol because of thiopurine failure and/ or hepatotoxicity. Subjects were given allopurinol concurrently with 6-MP/AZA, reduced to ~1 /3 of the original dose. Metabolite levels and their ratio (6MMP/ 6TGN) were compared pre- and post-allopurinol. Clinical remission was compared using the physician's global assessment, the Harvey-Bradshaw (Crohn's) or Lichtiger (UC) Index. Endoscopic remission was re-assessed in consenting patients using the CDEI or Mayo scores. Adverse events were recorded for all patients. Statistical comparison was analyzed by T or Fisher Exact (two-tailed) tests. Results: 50 patients (11 pediatric) were included. Allopurinol was discontinued in 4 cases, 3 due to intolerance + 1 for non-compliance. Among the 46 patients maintaining treatment for . 6 mo, the mean dose (SD) of AZA was reduced by 62.6%, from 174 (58) to 49 (16) mg/d (p ,0.01). The mean (SD) 6TGN, 6MMP and 6MMP/ 6TGN ratios before allopurinol were 171 (66), 9367 (5246) and 57.6 (30.9), respectively. On
954 Infliximab Maintenance Beyond One Year Prevents Postoperative Crohn's Disease Recurrence: Long-Term Follow-up From the Randomized Controlled Pilot Study Miguel Regueiro, Leonard Baidoo, Kevin E. Kip, Jason M. Swoger, David G. Binion, Jana G. Hashash, Wolfgang H. Schraut Background: Postoperative infliximab (IFX) reduces clinical and endoscopic Crohn's disease (CD) recurrence 1 yr after surgery. (Gastroenterol 2009) Benefit of IFX beyond 1 yr is not known. Aims: To determine whether continued IFX beyond 1 yr is effective at preventing long-term postop CD recurrence. Secondary aims include efficacy of starting IFX in response to postop endoscopic recurrence and whether IFX may be stopped in pts in remission. Methods: This is a prospective long-term follow-up study of the 24 pts from the original randomized controlled postop CD trial. Eleven pts had received IFX and 13 placebo, all underwent ileocolonoscopy 1 yr after surgery. At the completion of the 1 yr postop study, all pts were offered every 8 wk IFX 5mg/kg. Endoscopic recurrence was defined as a Rutgeerts ileal score of i2, i3, or i4. Surgical recurrence was defined as any pt requiring additional
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AGA Abstracts
vaccination". S2)88%(87/99) of the patients with previous vaccination, maintain tittles 4 months after start of anti-TNF. Anti-HBs tittles .100 after a follow-up of 36 months, were higher in patients with previous vaccination (S2) than in those who achieved "effective vaccination" during anti-TNF (S1)(83% vs 36%, p ,0,001; OR, 9). S3-4) In 2 of 29 antiHBc + patients(7%), HBV-DNA+ was detected in blood without reactivation. No reactivation was detected in the rest of HCV(n= 5) or HBsAg+(n=4). CONCLUSION: 1) Response to vaccination and revaccination is low in patients with anti-TNF, being the young age and anti-TNF monotherapy predictors of better response. 2) To have obtained seroprotection with the first vaccination is predictive of "effective vaccination" after revaccination. 3) The probability of maintaining a long-term effective vaccination is low when the vaccination is administered during anti-TNF. 4) Following the schedule of prevention and treatment, nor HBV nor HCV reactivation was observed in patients under anti-TNF.
953 Prolonged Exposure to Prednisone Is Decreasing in Children With Inflammatory Bowel Disease (IBD) During the Last Decade Julia Sorbara, David R. Mack, Trudy Lerer, Anthony R. Otley, Neal S. Leleiko, Anne M. Griffiths, Jonathan Evans, David J. Keljo, Marian D. Pfefferkorn, Joel R. Rosh, James Rick, Athos Bousvaros, Maria Oliva-Hemker, Jose Cabrera, Ryan Carvalho, Shehzad A. Saeed, Andrew B. Grossman, Michael Kappelman, Meredith C. Hitch, William A. Faubion, Marc Schaefer, Boris Sudel, James Markowitz, Jeffrey S. Hyams Background: Prednisone (Pred), a mainstay for therapy in children with IBD, may be associated with significant side effects. Increasing use of immunomodulators (IM) and antiTNFα agents over the last decade may have decreased utilization of Pred. We evaluated whether there has been a change in utilization over the last 10 years. Aim: To examine patterns of Pred use in pediatric IBD. Methods: Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. This is an observational cohort study enrolling patients ,16 years of age. Data are gathered at time of diagnosis (dx), 30 days later and quarterly thereafter. Therapies are by physician dictate, not protocol. Pred use was compared for patients enrolled between 2002-2005 (T1) and 2006-2010 (T2). Exposure was measured as number of quarters (Q) with any Pred use in the first year after dx. Results: A total of 1344 children with a final diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) with at least one year follow-up were enrolled (57% male, age at dx 11.8±3.1 years, Physician Global Assessment of disease severity (PGA) 29% mild, 52% moderate, 19% severe). Included were 654 (474 CD; 180 UC) subjects diagnosed during T1 and 690 (504 CD; 186 UC) during T2. The 2 groups were similar for gender (males: 58% vs. 56%), age of dx (CD: 11.7 vs. 12.1 years; UC: 10.9 vs. 13.1 years), PGA (31% vs. 27%; 52% vs. 53%; 17% vs. 20% for mild; moderate; severe disease; respectively). In the first 3 months following dx (Q1), Pred had been administered to a similar number of children with CD (73% vs. 70%) and with UC (71% vs. 71%) during the two time periods. By the end of the first year (Q4), a similar number of children with CD (78% vs. 75%) and UC (79% vs. 78%) had received Pred during both time periods. By Q4 however, patients in T1 had more quarters of Pred exposure than those from T2 (P,0.02). In addition, more patients from T1 compared to T2 received Pred in all 4 quarters of the first year (All IBD: 13% vs. 6%, P ,0.001; CD 11% vs. 5%, P ,0.001; UC: 20% vs. 10%, P,0.02). However, patients not receiving Pred in Q1 showed no difference in subsequent exposure between time periods (16% in both T1 and T2 received Pred during Q2 to Q4). As shown in the Table, among patients who received Pred in Q1 there were fewer UC patients receiving IM in the first year (P ,0.02) and increased use of biologic therapy by the end of Q1 (P,0.02) and by the end of Q4 (P ,0.01) in T2 compared to T1. Use of IM and biologic agents for CD patients receiving Pred in Q1 are consistent in direction but not statistically different (see Table) for the two time periods. Conclusion: Although any time Pred exposure is similar in the first 3 months of dx over the last 10 years, prolonged exposure has dramatically decreased in the latter time period. Use of Concomitant Therapies in Patients who Received Pred in First 3 Months Following Dx
Postoperative CD course per patient. Year 0 to 1 is the first postop year as part of the orginal RCT. Indication for initial and subsequent surgeries: B2=Stricture, B3=Fistula. IFX status (ON or OFF), endoscopic scores (i0-i4) and surgery recorded for first 5 yrs after initial (year 0) surgery. 955 Effect of Allopurinol on Clinical, Endoscopic and Metabolic Outcomes of Thiopurine Therapy in IBD Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G. Seidman
Q1=in the first 3 month of Dx; Q4=in the first year since Dx; IM=immunomodulators *P,0.01; **P,0.02 comparing 2--2-2005 vs. 2006-2010
Thiopurines are among the most commonly used maintenance medications for IBD. However, excessive methylation via the TPMT enzymatic route causes therapeutic failure, due to excessive production of 6-methyl-mercaptopurine (6MMP) and sub-therapeutic 6-thioguanine (6TGN) levels. Allopurinol has been shown to favourably alter 6MP metabolism, reducing 6MMP while favoring 6-TGN production. Our aim was to evaluate the clinical, metabolic and endoscopic impact of allopurinol in thiopurine non-responding patients. Method: Retrospective review of 50 consecutive cases treated with allopurinol because of thiopurine failure and/ or hepatotoxicity. Subjects were given allopurinol concurrently with 6-MP/AZA, reduced to ~1 /3 of the original dose. Metabolite levels and their ratio (6MMP/ 6TGN) were compared pre- and post-allopurinol. Clinical remission was compared using the physician's global assessment, the Harvey-Bradshaw (Crohn's) or Lichtiger (UC) Index. Endoscopic remission was re-assessed in consenting patients using the CDEI or Mayo scores. Adverse events were recorded for all patients. Statistical comparison was analyzed by T or Fisher Exact (two-tailed) tests. Results: 50 patients (11 pediatric) were included. Allopurinol was discontinued in 4 cases, 3 due to intolerance + 1 for non-compliance. Among the 46 patients maintaining treatment for . 6 mo, the mean dose (SD) of AZA was reduced by 62.6%, from 174 (58) to 49 (16) mg/d (p ,0.01). The mean (SD) 6TGN, 6MMP and 6MMP/ 6TGN ratios before allopurinol were 171 (66), 9367 (5246) and 57.6 (30.9), respectively. On
954 Infliximab Maintenance Beyond One Year Prevents Postoperative Crohn's Disease Recurrence: Long-Term Follow-up From the Randomized Controlled Pilot Study Miguel Regueiro, Leonard Baidoo, Kevin E. Kip, Jason M. Swoger, David G. Binion, Jana G. Hashash, Wolfgang H. Schraut Background: Postoperative infliximab (IFX) reduces clinical and endoscopic Crohn's disease (CD) recurrence 1 yr after surgery. (Gastroenterol 2009) Benefit of IFX beyond 1 yr is not known. Aims: To determine whether continued IFX beyond 1 yr is effective at preventing long-term postop CD recurrence. Secondary aims include efficacy of starting IFX in response to postop endoscopic recurrence and whether IFX may be stopped in pts in remission. Methods: This is a prospective long-term follow-up study of the 24 pts from the original randomized controlled postop CD trial. Eleven pts had received IFX and 13 placebo, all underwent ileocolonoscopy 1 yr after surgery. At the completion of the 1 yr postop study, all pts were offered every 8 wk IFX 5mg/kg. Endoscopic recurrence was defined as a Rutgeerts ileal score of i2, i3, or i4. Surgical recurrence was defined as any pt requiring additional
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AGA Abstracts
AGA Abstracts
vaccination". S2)88%(87/99) of the patients with previous vaccination, maintain tittles 4 months after start of anti-TNF. Anti-HBs tittles .100 after a follow-up of 36 months, were higher in patients with previous vaccination (S2) than in those who achieved "effective vaccination" during anti-TNF (S1)(83% vs 36%, p ,0,001; OR, 9). S3-4) In 2 of 29 antiHBc + patients(7%), HBV-DNA+ was detected in blood without reactivation. No reactivation was detected in the rest of HCV(n= 5) or HBsAg+(n=4). CONCLUSION: 1) Response to vaccination and revaccination is low in patients with anti-TNF, being the young age and anti-TNF monotherapy predictors of better response. 2) To have obtained seroprotection with the first vaccination is predictive of "effective vaccination" after revaccination. 3) The probability of maintaining a long-term effective vaccination is low when the vaccination is administered during anti-TNF. 4) Following the schedule of prevention and treatment, nor HBV nor HCV reactivation was observed in patients under anti-TNF.