P623 Once versus twice daily mesalazine to induce remission in paediatric ulcerative colitis: an investigator-initiated randomised controlled trial
D. Turner*1, B. Yerushalmi2, M. Kori3, E. Broide4, Y. Mozer-Glassberg5, R. Shaoul6, K.-L. Kolho7, E. Shteyer8, H. Shamaly9, O. Ledder10, S. Cohen11, S. Peleg12, A. On13, A. Levine14
1Shaare Zedek Medical Centre, Institute of Paediatric Gastroenterology, Jerusalem, Israel, 2Soroka Medical Centre, Beer Sheva, Israel, 3Kaplan Hospital, Rehovot, Israel, 4Asaff Harofeh, Tel Aviv, Israel, 5Schneider’s Children Hospital, Petach Tikva, Israel, 6Rambam medical Centre, Haifa, Israel, 7Children´s Hospital, University of Helsinki, Helsinki, Finland, 8Hadassah Medical Centre, Jerusalem, Israel, 9French Hospital, Nazareth, Israel, 10Shaare Zedek Medical Centre, Jerusalem, Israel, 11Tel Aviv Medical Centre, Tel Aviv, Israel, 12Emek Medical Centre, Afula, Israel, 13Poria, Tiberias, Israel, 14Wolfson Medical Centre, Holon, Israel
Several trials in adults have suggested that once daily 5-ASA may be as or more effective than twice daily dosing in ulcerative colitis (UC). There are no similar studies in children. In this 9-week induction investigator-blinded randomised controlled trial, we aimed to compare the effectiveness and safety of once- vs twice-daily Pentasa in paediatric UC.
Children, 4–18 years with a PUCAI of 10–55 points were eligible for enrolment if they were not treated with effective 5-ASA dose, in 13 centres in Israel and Finland. Children were randomised into 2 arms: once- (OD) and twice (BID)-daily Pentasa, using a weight-based dosing table (max 3gr/d) and computer generated randomisation. Primary outcome was week 6 mean PUCAI score, which has a high concordance with sigmoidoscopy in children. Physicians who completed the PUCAI were blinded to the treatment allocation they analysed the data. Further, 6 visits were schedules until week 9 when safety was assessed. Missing data were imputed using the last observation carried forward (LOCF) method; analyses were performed using the modified ITT approach.
In total, 86 children were randomised, and 3 were excluded (1 withdrew consent before receiving study drug, 1 Crohn’s, and 1 C. Difficile). Next, 83 were analysed: 43 in the OD and 40 in the BID groups (mean age 14 ± 2.7 years, range 7–18; 43 (52%) males; 51 (62%) extensive colitis). Further, 31 (38%) dropped because of disease aggravation; 7 (8%) were lost to follow-up; and 45 (54%) completed the primary visit. There was no difference in completion rates between the OD (28 [65%]) and BID (28 [70%]) arms; p > 0.2. Mean PUCAI scores at weeks 2, 3, 6, and 9 were similar between the OD vs BID arms (24 ± 17 vs 21 ± 16, 19 ± 17 vs 17 ± 17, 23 ± 20 vs 19 ± 20, and 22 ± 21 vs 20 ± 20; all p > 0.2). The proportion of children who responded (change in PUCAI ≥ 20) was similar at both weeks 6 and 9 (25 (60%) vs 25 (63%); p = 0.78, and 25 (60%) vs 22 (55%); p = 0.68, respectively). The proportion of children in remission (PUCAI < 10) at week 6 and 9 was similar between the OD and BID groups (13 [30%] vs 16 [40%]; P = 0.35 and 15 [35%] vs 17 [43%]; p = 0.48). Mean reported compliance with treatment was 94% in the OD vs 89% in the BID arms; p = 0.17. There were no differences in the mean values of CRP, albumin, haemoglobin, and ESR at week 6 (all p >0.1). Most adverse events were related to disease aggravation, and the rate of serious adverse events was similar (p > 0.2); there were 9 events possibly related to the study medication with similar occurrence (4 vs 5).
There were no differences in effectiveness, safety and compliance when prescribing Pentasa once or twice daily for inducing remission in active UC. This IIS study was partially supported by an educational grant from Ferring, which was not involved in the trial or abstract preparation.