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P149 - Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME study
S70
Poster Presentations
label adalimumab 40 mg eow and could subsequently change to weekly treatment. At the end of CHARM (56 weeks), patients were eligible to enroll in an open-label extension trial (ADHERE), during which blinded patients received openlabel adalimumab 40 mg eow, and patients receiving open-label adalimumab eow or weekly continued their regimens. Patients could switch to weekly dosage for flares/nonresponse. Dosage decrease was not allowed. Post-hoc analyses of maintenance of remission (CDAI < 150) and response (drop in CDAI 70 [CR-70] or 100 [CR-100] points) [data not shown] were performed for patients initially randomized to adalimumab who were in remission at Week 56 of CHARM. Patients randomized to placebo were not analyzed. Remission rates were calculated using nonresponder imputation (NRI) and last-observationcarried-forward (LOCF) analyses. Results: A total of 467 patients enrolled in the open-label extension trial. Remission results for the 145 patients initially randomized to adalimumab who were in remission at the end of CHARM are shown in the table. In the LOCF analysis, 83% (120 of 145) of patients were in remission 3 years after enrollment in CHARM (Week 108 of the open-label extension). Remission rates for adalimumab-treated patients through 3 years Week of OLE trial following CHARM
Week Week Week Week
24 AHDERE 48 ADHERE 60 ADHERE* 108 ADHERE*
Remission, n (%) NRI (N = 145)
LOCF (N = 145)
113 (78) 111 (77) 105 (72) 93 (64)
118 123 122 120
(81) (85) (84) (83)
*2 and 3 years from CHARM baseline represent Weeks 60 and 108 in the open-label extension (ADHERE), respectively. OLE = open-label extension. Conclusions: Adalimumab demonstrated sustained efficacy in maintaining CD remission through 3 years of therapy. The majority of adalimumab-treated patients in remission after 1 year in CHARM maintained remission for an additional 2 years in an open-label extension trial. Reference(s) [1] Colombel J-F, et al. Gastroenterology. 2007; 132: 52 65. P149 Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME study J. Coelho *, L. Beaugerie, J.F. Colombel, X. H´ ebuterne, E. Lerebours, M. Lemann, P. Baumer, J. Cosnes, A. Bourreille, J.P. Gendre, P. Seksik, A. Blain, E.H. Metman, A. Nisard, G. Cadiot, M. Veyrac, B. Coffin, F. Carrat, P. Marteau. Lariboisiere ’s Hospital, Paris, France Introduction: Data on safety of thiopurines during pregnancy in women with inflammatory bowel disease (IBD) are scarce (especially on the risk of congenital abnormalities). The aim of this study was to evaluate the pregnancy outcome in women exposed to thiopurines. Patients and Methods: Cases of pregnancies were registered and documented in the CESAME cohort between may 2004 and october 2007. The information collected included: last menstrual date, delivery term, pregnancy outcome details as spontaneous abortion, therapeutic abortion, prematurity (gestational age of under 37 weeks of gestation), birth weight and height, congenital abnormality, medication history during each trimester, smoking history and alcohol consumption. Data were compared between women exposed to thiopurines (alone
or in combination with another treatment aminosalicylates, corticosteroids or anti-TNFa), women receiving another drug than thiopurines and patients without any medication. Results: This series included 215 pregnancies in 204 women with a median age of 28.4 years, 75.7% had Crohn’s disease (CD), 21.8% ulcerative colitis (UC) and 2.5% an unclassified colitis. The mean disease duration was 6.8 years. There were 138 live births (142 newborns including 4 twins) (Table 1). No significant differences were found among the 3 groups with respect to interrupted pregnancies (36%, 33%, 40% respectively). The mean birth weight was 3135 g. Table 1 IBD treatment outcome
Thiopurines (n = 86)
Others than thiopurines (n = 84)
None (n = 45)
Live births, n Prematurity, n (%)* Low birth weight (<2500 g), n (%)* Congenital abnormalities, n (%)*
55 12 (21.8%) 8 (14.5%) 2 (3.6%)
56 9 (16%) 7 (12.5%) 3 (5.3%)
27 4 (14.8%) 2 (7.4%) 1 (3.7%)
*In proportion of births. Differences were not significant (exact Fisher test).
Conclusion: The results of this large cohort indicate that thiopurines use during pregnancy is not associated with increased congenital abnormalities risk. The high incidence of hypotrophy and prematurity did not differ between the groups and may correlate to the underlying disease. P150 Tolerability and safety of accelerated infliximab infusions: a prospective referral center registry and patient survey G. Van Assche *, S. Vermeire, M. Noman, E. Weyts, M. Vermeyen, A. Vleminckx, C. Amant, P. Rutgeerts. University of Leuven Hospitals, Leuven, Belgium Background: Anti-TNF antibodies require parenteral administration and for infliximab (IFX) this implies regular visits to an infusion unit. In rheumatoid arthritis patients onIFX maintenance therapy, shorter infusion times are advocated in patients tolerating induction therapy. The aim of this study was to prospectively assess the safety and tolerability of shortening IFX infusion times using standard operating procedures. Furthermore, we anonymously surveyed patients on the impact of their IV therapy on quality of life (QOL). Methods and Results: 177 patients (age 40±16 yrs., 51% female) were included in 20 consecutive days (March-April 2008) and all safety and infusion-related parameters were prospectively registered by the unit nurses and physicians. In 95% of patients an IV line was placed in a single attempt (max. 3). Our IFX protocol allows one hour infusion from the 5th infusion onwards and provided that previous infusions have not generated allergic reactions. Median nr. of IFX infusions was 16 (IQR:9 26, all scheduled maintenance), with one hour infusions in 66.2% and prophylaxis for infusion reactions in 23.2% (>2.5 hrs. infusion). Infusion reactions occurred in only 4 patients (2%, all mild or moderate), and 2 of these reactions occurred during a 1 hour infusion, but never during the first shortened infusion.. No delayed infusion reactions were observed. The Median duration of the visit to the infusion unit was 1:52 hrs overall with, 1:35 hrs (IQR 1:25 1:50) for one hr. infusions and a median of 3:20 hrs (2:50 3:45, p < 0.0001) for infusions with prophylaxis. The patients survey (5 points Likert scale) learned that 81% of patients were very satisfied. A minority of patients felt that the repeated infusions had a strong or considerable impact on work/studies (37%), social/family life (35%). For 15% side effects had a considerable impact on QOL. Conclusions: Accelerated 1 hr. infusions with infliximab are well tolerated by patients with IBD and reduce the total infusion
Poster Presentations
label adalimumab 40 mg eow and could subsequently change to weekly treatment. At the end of CHARM (56 weeks), patients were eligible to enroll in an open-label extension trial (ADHERE), during which blinded patients received openlabel adalimumab 40 mg eow, and patients receiving open-label adalimumab eow or weekly continued their regimens. Patients could switch to weekly dosage for flares/nonresponse. Dosage decrease was not allowed. Post-hoc analyses of maintenance of remission (CDAI < 150) and response (drop in CDAI 70 [CR-70] or 100 [CR-100] points) [data not shown] were performed for patients initially randomized to adalimumab who were in remission at Week 56 of CHARM. Patients randomized to placebo were not analyzed. Remission rates were calculated using nonresponder imputation (NRI) and last-observationcarried-forward (LOCF) analyses. Results: A total of 467 patients enrolled in the open-label extension trial. Remission results for the 145 patients initially randomized to adalimumab who were in remission at the end of CHARM are shown in the table. In the LOCF analysis, 83% (120 of 145) of patients were in remission 3 years after enrollment in CHARM (Week 108 of the open-label extension). Remission rates for adalimumab-treated patients through 3 years Week of OLE trial following CHARM
Week Week Week Week
24 AHDERE 48 ADHERE 60 ADHERE* 108 ADHERE*
Remission, n (%) NRI (N = 145)
LOCF (N = 145)
113 (78) 111 (77) 105 (72) 93 (64)
118 123 122 120
(81) (85) (84) (83)
*2 and 3 years from CHARM baseline represent Weeks 60 and 108 in the open-label extension (ADHERE), respectively. OLE = open-label extension. Conclusions: Adalimumab demonstrated sustained efficacy in maintaining CD remission through 3 years of therapy. The majority of adalimumab-treated patients in remission after 1 year in CHARM maintained remission for an additional 2 years in an open-label extension trial. Reference(s) [1] Colombel J-F, et al. Gastroenterology. 2007; 132: 52 65. P149 Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME study J. Coelho *, L. Beaugerie, J.F. Colombel, X. H´ ebuterne, E. Lerebours, M. Lemann, P. Baumer, J. Cosnes, A. Bourreille, J.P. Gendre, P. Seksik, A. Blain, E.H. Metman, A. Nisard, G. Cadiot, M. Veyrac, B. Coffin, F. Carrat, P. Marteau. Lariboisiere ’s Hospital, Paris, France Introduction: Data on safety of thiopurines during pregnancy in women with inflammatory bowel disease (IBD) are scarce (especially on the risk of congenital abnormalities). The aim of this study was to evaluate the pregnancy outcome in women exposed to thiopurines. Patients and Methods: Cases of pregnancies were registered and documented in the CESAME cohort between may 2004 and october 2007. The information collected included: last menstrual date, delivery term, pregnancy outcome details as spontaneous abortion, therapeutic abortion, prematurity (gestational age of under 37 weeks of gestation), birth weight and height, congenital abnormality, medication history during each trimester, smoking history and alcohol consumption. Data were compared between women exposed to thiopurines (alone
or in combination with another treatment aminosalicylates, corticosteroids or anti-TNFa), women receiving another drug than thiopurines and patients without any medication. Results: This series included 215 pregnancies in 204 women with a median age of 28.4 years, 75.7% had Crohn’s disease (CD), 21.8% ulcerative colitis (UC) and 2.5% an unclassified colitis. The mean disease duration was 6.8 years. There were 138 live births (142 newborns including 4 twins) (Table 1). No significant differences were found among the 3 groups with respect to interrupted pregnancies (36%, 33%, 40% respectively). The mean birth weight was 3135 g. Table 1 IBD treatment outcome
Thiopurines (n = 86)
Others than thiopurines (n = 84)
None (n = 45)
Live births, n Prematurity, n (%)* Low birth weight (<2500 g), n (%)* Congenital abnormalities, n (%)*
55 12 (21.8%) 8 (14.5%) 2 (3.6%)
56 9 (16%) 7 (12.5%) 3 (5.3%)
27 4 (14.8%) 2 (7.4%) 1 (3.7%)
*In proportion of births. Differences were not significant (exact Fisher test).
Conclusion: The results of this large cohort indicate that thiopurines use during pregnancy is not associated with increased congenital abnormalities risk. The high incidence of hypotrophy and prematurity did not differ between the groups and may correlate to the underlying disease. P150 Tolerability and safety of accelerated infliximab infusions: a prospective referral center registry and patient survey G. Van Assche *, S. Vermeire, M. Noman, E. Weyts, M. Vermeyen, A. Vleminckx, C. Amant, P. Rutgeerts. University of Leuven Hospitals, Leuven, Belgium Background: Anti-TNF antibodies require parenteral administration and for infliximab (IFX) this implies regular visits to an infusion unit. In rheumatoid arthritis patients onIFX maintenance therapy, shorter infusion times are advocated in patients tolerating induction therapy. The aim of this study was to prospectively assess the safety and tolerability of shortening IFX infusion times using standard operating procedures. Furthermore, we anonymously surveyed patients on the impact of their IV therapy on quality of life (QOL). Methods and Results: 177 patients (age 40±16 yrs., 51% female) were included in 20 consecutive days (March-April 2008) and all safety and infusion-related parameters were prospectively registered by the unit nurses and physicians. In 95% of patients an IV line was placed in a single attempt (max. 3). Our IFX protocol allows one hour infusion from the 5th infusion onwards and provided that previous infusions have not generated allergic reactions. Median nr. of IFX infusions was 16 (IQR:9 26, all scheduled maintenance), with one hour infusions in 66.2% and prophylaxis for infusion reactions in 23.2% (>2.5 hrs. infusion). Infusion reactions occurred in only 4 patients (2%, all mild or moderate), and 2 of these reactions occurred during a 1 hour infusion, but never during the first shortened infusion.. No delayed infusion reactions were observed. The Median duration of the visit to the infusion unit was 1:52 hrs overall with, 1:35 hrs (IQR 1:25 1:50) for one hr. infusions and a median of 3:20 hrs (2:50 3:45, p < 0.0001) for infusions with prophylaxis. The patients survey (5 points Likert scale) learned that 81% of patients were very satisfied. A minority of patients felt that the repeated infusions had a strong or considerable impact on work/studies (37%), social/family life (35%). For 15% side effects had a considerable impact on QOL. Conclusions: Accelerated 1 hr. infusions with infliximab are well tolerated by patients with IBD and reduce the total infusion