Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis
W Kruis, L Jonaitis, J Pokrotnieks, T L Mikhailova, M Horynski, M Bátovský, Y S Lozynsky, Y Zakharash, I Rácz, K Kull, A Vcev, M Faszczyk, K Dilger, R Greinwald, R Mueller, International Salofalk OD Study Group, B Vucelic, D Stimac, I Krznaric, K Baraba, A Vcev, S Mihaljevic, E Khaznadar, S Mise, Z Sundov, M Kozic, I Klarin, Z Matas, D Kasun, J Turcinov, R Marcelic, M Lukas, L Gabalec, P Kohout, J Kykal, J Polacek, T Vich, K Kull, R Salupere, P Koiva, K Labotkin, H Remmel, W Kruis, S Böhm, M Behnke, J Kuth, J Hämling, E Meier, M Schumacher, T Zeisler, J Zeus, I Rácz, A Szabó, G Pécsi, M Csöndes, T Kárász, H Saleh, J Banai, T Szamosi, Z Czeglédi, P Demeter, R Sike, K Sárdi, J Penyige, F Huoránszki, L Balint, Z Döbrönte, L Lakner, L Lakatos, G Mester, Z Tulassay, L Herszényi, M Juhász, P Miheller, A Neméth, L Újszászy, A Grenda, B Velösy, Z Virányi, Z Dubravcsik, J Papp, P Lakatos, J Lonovics, F Nagy, T Molnár, A Tiszai, S Bar-Meir, H Fidder, S Ben-Horin, I Dotan, R Eliakim, I Chermesh, M Faszczyk, A Berezovsky, G Katz, A Fich, S Odes, D Keret, V Mindrul, A Lavy, D Keren, E Melzer, Y Binder, Y Niv, G Fraser, E Gal, Z Ibrahim, E Scapa, E Broide, N Kimchi, J Pokrotnieks, A Pukitis, M Ergle, J Derova, A Derovs, L Kupcinskas, L Jonaitis, G Kiudelis, G Acute, V Vainoriute, V Metrikis, A Cepulis, K Adamonis, A Modzeliauskas, N Samalavicius, A Buineviciute, G Radziunas, G Simulionis, V Kuolas, S Petrauskas, R Vanagaitiene, A Navikiene, A Jablonskis, K Marlicz, H Jaroszewicz-Heigelmann, M Wasilewicz, L Szczepanski, R Zwolak, D Chudzik, M Piotrowski, M Mazurek, A Kopon, E Kopon, M Horynski, D Kleczkowski, W Latos, A Sieron, K Sieron-Stoltny, A Wysokinski, R Grodzienski, W Kosikowski, J Drabko, E Belousova, T Mishurovskaya, I Nikulina, V Grinevich, A Pershko, I Gubonina, A Gorelov, E Sishkova, D Raspereza, T Tinyakova, T Mikhailova, O Golovenko, L Mayat, P Makarchuk, N Malakhova, K Zhidkov, F Albegova, M Vasilukova, M Yurkov, A Savitsky, I Mitrofanova, E Yakovenko, A Yakovenko, A Pryanishnikova, N Agafonova, A Isanov, I Bakulin, V Novozhenov, V Ruseikin, M Ivanova, K Malabaev, I Eroshenko, D Stanke, M Bátovský, B Barický, B Pekárková, B Pekarek, M Stefanovic, Z Tosovic, L Ljepovic, B Gorjup, B Gregoric, A Dorofeyev, K Lynevskaya, O Rassokhina, I Lozynskyy, M Lozynska, S Golovchansky, I Kolyada, M Zakharash, Y Zakharash, S Mouzyka, T Kravchenko, W Kruis, L Jonaitis, J Pokrotnieks, T L Mikhailova, M Horynski, M Bátovský, Y S Lozynsky, Y Zakharash, I Rácz, K Kull, A Vcev, M Faszczyk, K Dilger, R Greinwald, R Mueller, International Salofalk OD Study Group, B Vucelic, D Stimac, I Krznaric, K Baraba, A Vcev, S Mihaljevic, E Khaznadar, S Mise, Z Sundov, M Kozic, I Klarin, Z Matas, D Kasun, J Turcinov, R Marcelic, M Lukas, L Gabalec, P Kohout, J Kykal, J Polacek, T Vich, K Kull, R Salupere, P Koiva, K Labotkin, H Remmel, W Kruis, S Böhm, M Behnke, J Kuth, J Hämling, E Meier, M Schumacher, T Zeisler, J Zeus, I Rácz, A Szabó, G Pécsi, M Csöndes, T Kárász, H Saleh, J Banai, T Szamosi, Z Czeglédi, P Demeter, R Sike, K Sárdi, J Penyige, F Huoránszki, L Balint, Z Döbrönte, L Lakner, L Lakatos, G Mester, Z Tulassay, L Herszényi, M Juhász, P Miheller, A Neméth, L Újszászy, A Grenda, B Velösy, Z Virányi, Z Dubravcsik, J Papp, P Lakatos, J Lonovics, F Nagy, T Molnár, A Tiszai, S Bar-Meir, H Fidder, S Ben-Horin, I Dotan, R Eliakim, I Chermesh, M Faszczyk, A Berezovsky, G Katz, A Fich, S Odes, D Keret, V Mindrul, A Lavy, D Keren, E Melzer, Y Binder, Y Niv, G Fraser, E Gal, Z Ibrahim, E Scapa, E Broide, N Kimchi, J Pokrotnieks, A Pukitis, M Ergle, J Derova, A Derovs, L Kupcinskas, L Jonaitis, G Kiudelis, G Acute, V Vainoriute, V Metrikis, A Cepulis, K Adamonis, A Modzeliauskas, N Samalavicius, A Buineviciute, G Radziunas, G Simulionis, V Kuolas, S Petrauskas, R Vanagaitiene, A Navikiene, A Jablonskis, K Marlicz, H Jaroszewicz-Heigelmann, M Wasilewicz, L Szczepanski, R Zwolak, D Chudzik, M Piotrowski, M Mazurek, A Kopon, E Kopon, M Horynski, D Kleczkowski, W Latos, A Sieron, K Sieron-Stoltny, A Wysokinski, R Grodzienski, W Kosikowski, J Drabko, E Belousova, T Mishurovskaya, I Nikulina, V Grinevich, A Pershko, I Gubonina, A Gorelov, E Sishkova, D Raspereza, T Tinyakova, T Mikhailova, O Golovenko, L Mayat, P Makarchuk, N Malakhova, K Zhidkov, F Albegova, M Vasilukova, M Yurkov, A Savitsky, I Mitrofanova, E Yakovenko, A Yakovenko, A Pryanishnikova, N Agafonova, A Isanov, I Bakulin, V Novozhenov, V Ruseikin, M Ivanova, K Malabaev, I Eroshenko, D Stanke, M Bátovský, B Barický, B Pekárková, B Pekarek, M Stefanovic, Z Tosovic, L Ljepovic, B Gorjup, B Gregoric, A Dorofeyev, K Lynevskaya, O Rassokhina, I Lozynskyy, M Lozynska, S Golovchansky, I Kolyada, M Zakharash, Y Zakharash, S Mouzyka, T Kravchenko
Abstract
Background: Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited.
Aim: To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis.
Methods: A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline.
Results: The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group.
Conclusion: Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.
© 2010 Blackwell Publishing Ltd.
Source: PubMed