BACKGROUND: Many patients with ulcerative colitis (UC) respond to mesalamine therapy within 8 weeks. Those not achieving remission after 8 weeks are often treated with steroids or other immunosuppressive therapies. This study aimed to determine the effect of 8 weeks' high-dose MMX mesalamine extension therapy in patients with active, mild-to-moderate UC who had previously failed to achieve complete remission in 2 phase III, double-blind, placebo-controlled studies of MMX mesalamine (SPD476-301 and -302). METHODS:Patients with active, mild-to-moderate UC who did not achieveclinical and endoscopic remission after <or=8 weeks' treatment with MMX mesalamine (2.4 or 4.8 g/day), ASACOL (mesalamine) delayed-release tablets 2.4 g/day, or placebo in the phase III studies received MMX mesalamine 4.8 g/day for 8 weeks. The aim was to assess remission at week 8, defined as a total modified UC Disease Activity Index score of <or=1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment score and sigmoidoscopy score of <or=1, no mucosal friability, and a >or=1 point reduction from baseline in sigmoidoscopy score. RESULTS: Overall, 304 patients who entered this acute extension study were evaluated; 59.5% achieved remission at week 8. Remission rates were similar irrespective of prior treatment in the initial acute phase III studies. CONCLUSIONS: Most patients with mild-to-moderate UC who fail to achieve remission with up to 8 weeks' initial mesalamine therapy can achieve clinical and endoscopic remission following a further 8 weeks' treatment with high-dose MMX mesalamine therapy, thereby avoiding step-up therapy.
RCT Entities:
BACKGROUND: Many patients with ulcerative colitis (UC) respond to mesalamine therapy within 8 weeks. Those not achieving remission after 8 weeks are often treated with steroids or other immunosuppressive therapies. This study aimed to determine the effect of 8 weeks' high-dose MMX mesalamine extension therapy in patients with active, mild-to-moderate UC who had previously failed to achieve complete remission in 2 phase III, double-blind, placebo-controlled studies of MMX mesalamine (SPD476-301 and -302). METHODS:Patients with active, mild-to-moderate UC who did not achieve clinical and endoscopic remission after <or=8 weeks' treatment with MMX mesalamine (2.4 or 4.8 g/day), ASACOL (mesalamine) delayed-release tablets 2.4 g/day, or placebo in the phase III studies received MMX mesalamine 4.8 g/day for 8 weeks. The aim was to assess remission at week 8, defined as a total modified UC Disease Activity Index score of <or=1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment score and sigmoidoscopy score of <or=1, no mucosal friability, and a >or=1 point reduction from baseline in sigmoidoscopy score. RESULTS: Overall, 304 patients who entered this acute extension study were evaluated; 59.5% achieved remission at week 8. Remission rates were similar irrespective of prior treatment in the initial acute phase III studies. CONCLUSIONS: Most patients with mild-to-moderate UC who fail to achieve remission with up to 8 weeks' initial mesalamine therapy can achieve clinical and endoscopic remission following a further 8 weeks' treatment with high-dose MMX mesalamine therapy, thereby avoiding step-up therapy.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059