Table 1

Quality of care—using specific aspects of efficacy to inform induction of remission with mesalazine

Pivotal studies	Dose–response effect	Timescale of symptom changes	Extent of disease	Mucosal healing*
Asacol^®—ASCEND I, II and III15 31 32 33 34 35 Randomised, active-controlled studies of mesalazine 2.4 vs 4.8 g/day31 32 33 1459 patients with mild to moderately active UC†‡ Primary endpoint: treatment success at week 6 (based on PGA and clinical assessments)	Focusing on moderately active UC in isolation provided evidence that high-dose mesalazine may be particularly beneficial in this patient group.31 32	Median time to resolution of both rectal bleeding and stool frequency with mesalazine 4.8 g/day: 19 days; symptom relief at day 14 was associated with relief at 6 weeks in most patients.15	Subgroup analysis demonstrated similar efficacy across all disease extents evaluated (proctitis to pancolitis).34	80% of patients achieved mucosal healing (endoscopy score 0 or 1), and 32% achieved complete healing (endoscopy score 0) after 6 weeks’ treatment with mesalazine 4.8 g/day for moderately active UC.35
Mezavant XL^®—MMX36 37 38 39 40 Two randomised placebo-controlled studies of mesalazine 2.4 and 4.8 g/day versus placebo38 39 623 patients with mild to moderately active UC† Primary endpoint: clinical and endoscopic remission at 8 weeks (based on modified UCDAI and clinical assessments)	Similar efficacy results were observed with mesalazine 2.4 and 4.8 g/day.40	Median time to resolution of both rectal bleeding and stool frequency with mesalazine 4.8 g/day: 26 days.36	Subgroup analysis demonstrated similar efficacy across all disease extents evaluated (proctitis was excluded); disease extent was not a predictor of remission, and treatment effect was not dependent on the extent of disease.37	32% of patients achieved complete mucosal healing (sigmoidoscopy score 0) after 8 weeks’ treatment with either 2.4 or 4.8 g/day.40
Octasa^®—Feagan et al, 201341 Randomised, double-blind placebo-controlled study of mesalazine 4.8 g/day versus placebo41 281 patients with mild to moderately active UC† Primary endpoint: clinical remission (UCDAI scores of 0 for stool frequency and bleeding, no faecal urgency)			Patients with proctitis had 15 cm disease only.41	At week 6, in the intention to treat (ITT) population, 45.7% of patients achieved endoscopic remission (sigmoidoscopic score of ≤1) with mesalazine 4.8 g/day, compared with 24.8% with placebo (p<0.001).41
Pentasa^®—PINCE42 43 and MOTUS44 45 46 Randomised, controlled studies of oral mesalazine 4 g/day: – PINCE: oral versus oral+enema (4+1 g/day)43 MOTUS:‡ BD oral mesalazine (+ enema 1 g/day)44 127 and 206 patients with mild to moderately active UC, respectively† Primary endpoint: remission rate (based on UCDAI) at 4 weeks (PINCE) and 8 weeks (MOTUS)		63% of patients experienced overall improvement at day 14 with oral mesalazine 4 g/day+mesalazine enema 1 g/day for mild to moderately active UC.42 Median time to remission with BD oral mesalazine 4 g/day: 28 days.46	BD mesalazine showed similar efficacy in patients with left-sided UC compared with the MOTUS study population as a whole (includes patients with distal, left-sided and extensive UC and pancolitis).45 The PINCE study included only patients with extensive UC.	71.1% of patients achieved mucosal healing (UC-DAI endoscopic mucosal appearance score ≤1) with BD treatment (p=0.007).46
Salofalk^®—Kruis et al, 200947 Randomised, double-blind study of oral mesalazine 3 g/day, OD versus TDS47 381 patients with active UC† Primary endpoint: clinical remission rate at 8 weeks (CAI ≤4)		Median time to first resolution of symptoms with OD and TDS mesalazine: 12 and 16 days, respectively (p=n.s.).47	Significantly more patients with proctosigmoiditis achieved remission with OD versus TDS treatment (p=0.0298).47 In the OD group, significantly more patients with proctosigmoiditis achieved remission, compared with those with proximal disease (p=0.0247; proctitis was excluded).47	Endoscopic remission (endoscopic index <4) was achieved by 71% and 70% of patients in the OD and TDS groups, respectively.47
Implications for practice	The dose–response effect with mesalazine can be difficult to interpret,48 and the selection of a mesalazine dose should be made on an individual basis. High-dose mesalazine (4.8 g/day) may be beneficial for patients with moderately active UC.14	Mesalazine provides rapid resolution of symptoms. Moreover, the observations suggest that 2 weeks may be a practical timepoint at which to assess treatment response and plan subsequent steps.	Although some of the key studies were restricted to specific extents of UC, subgroup analyses indicate that mesalazine shows efficacy across all disease extents.	Mucosal healing may improve long-term outcomes, and mesalazine is an effective option for inducing and maintaining mucosal healing in many patients.

*Definitions of mucosal healing and endoscopic assessments vary between studies, making direct comparisons challenging.
†Patient numbers refer to the total number of patients randomised in the respective studies. Note that not all randomised patients were included in the analyses, and intent-to-treat, per-protocol and subgroup analysis sets varied between studies (refer to the original studies for full details of the study populations).
‡Data provided are reflective of currently licensed indications in the UK.
BD, twice daily; CAI, clinical activity index; n.s., not significant; OD, once daily; PGA, physician's global assessment; TDS, three times daily; ITT, intention to treat; UCDAI, ulcerative colitis disease activity index.