Area Editoriale
In controtendenza rispetto all'attuale stato dell'arte, i dati di questo trial controllato multicentrico mostrano una maggior efficacia di un alto dosaggio di mesalazina (3 gr al giorno) rispetto al dosaggio di 1,5 gr al giorno, sia in dose unica sia in tre dosi giornalliere.
Tuttavia, in maniera del tutto contro-intuitiva, le differenze si assottigliano (e la significatività statistica viene persa) nel sottogruppo di pazienti in remissione clinica ma con lievi segni endoscopici di infiammazione, e questo per una apparente MAGGIOR efficacia della terapia a bassi dosaggi in questo sottogruppo.
Dati interessanti, ma necessitanti ulteriori conferme
W Kruis, L Jonaitis, J Pokrotnieks, T L Mikhailova, M Horynski, M Batovsky´, YS Lozynsky, Y Zakharash, I Rcz, K Kull, A Vcev, M Faszczyk, K Dilger, R Greinwald, R. Mueller & the International Salofalk OD Study Group. Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis. Aliment Pharmacol Ther 2011; 33: 313-322
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.