Rationale and impact

This section briefly explains why the committee made the recommendations and how they might affect practice. It links to details of the evidence and a full description of the committee's discussion.

Inducing remission in people with mild-to-moderate ulcerative colitis

Recommendations 1.2.1 to 1.2.14

Why the committee made the recommendations

Proctitis

The evidence showed that topical aminosalicylates (suppositories or enema) are the most effective treatments for achieving remission in people with mild-to-moderate proctitis, so these were recommended as first-line treatments. The evidence did not show any difference in effectiveness between enema and suppository.

Topical aminosalicylates alone are recommended for up to 4 weeks because the evidence showed that they were the most effective treatment within this timeframe. There was no direct evidence for combining topical and oral aminosalicylates for people with proctitis. However, evidence showed that this combination was effective for people with proctosigmoiditis, and the committee agreed that this evidence was also applicable to people with proctitis alone. The committee chose not to specify a dose for the oral aminosalicylate. It preferred to leave it open to clinical judgment depending on the specific situation (for example, the clinician could give a low dose if the person had not taken an aminosalicylate before, or a high dose if the person was already taking a low dose).

Some people will not achieve remission with topical and oral aminosalicylates. In clinical practice, oral or topical corticosteroids are commonly added at this stage, but there was no evidence on this combination. The committee agreed that, based on their experience, adding a topical or oral corticosteroid should be an option at this stage.

Despite the lack of direct evidence for the effectiveness of topical or oral corticosteroids, the committee agreed that, based on their experience, these should also be an option for people who cannot tolerate aminosalicylates.

Some people decline topical treatment, preferring oral to topical aminosalicylates. This is more common in children and young people, although proctitis is not common in this group. As the evidence showed that oral aminosalicylates are not as effective at inducing remission, the committee thought it was important to explain this to people who decline topical aminosalicylates.

There was cost-effectiveness evidence showing that using an immunomodulator as the next line of treatment after oral or topical corticosteroids and oral aminosalicylate produced greater health benefits at lower total costs than other strategies. However, the clinical evidence on topical immunomodulators was limited and it was unclear how applicable it was to UK clinical practice. Because of this, the committee recommended the sequence without this final treatment, and recommended further research on topical immunomodulators.

Proctosigmoiditis or left-sided ulcerative colitis

There is evidence that topical aminosalicylates are effective for achieving remission in people with mild-to-moderate proctosigmoiditis or left-sided ulcerative colitis. In the committee's experience topical aminosalicylates also work faster and more effectively than topical corticosteroids. Topical aminosalicylates alone are recommended for up to 4 weeks because the evidence showed that they were effective within this timeframe. Cost-effectiveness evidence also showed that treatment sequences starting with topical aminosalicylates produced greater health benefits and incurred lower total costs than other strategies.

There is no direct evidence for the effectiveness of high-dose oral aminosalicylates combined with either topical aminosalicylates or topical corticosteroids. However, there is evidence that topical treatments or high-dose oral aminosalicylates individually provide some benefit. Therefore, the committee agreed it was reasonable to recommend combinations of these if remission is not achieved. While there was limited evidence for oral corticosteroids, in the committee's experience an oral corticosteroid may benefit people with proctosigmoiditis or left-sided disease if further treatment is needed. As a result, they recommended oral corticosteroids with oral aminosalicylates instead of topical treatment for these people. This reflects current practice for people who do not achieve remission with topical treatments and high-dose oral aminosalicylates.

Extensive ulcerative colitis

The evidence showed that people with mild-to-moderate extensive ulcerative colitis would benefit most from a combination of high-dose oral aminosalicylates with topical aminosalicylates as first-line treatment. High-dose oral aminosalicylates combined with topical aminosalicylates are recommended for up to 4 weeks, because in the committee's experience they are the most effective treatment within this timeframe. There is evidence that an oral corticosteroid combined with a high-dose oral aminosalicylate is also effective, so the committee recommended this combination if remission is not achieved with aminosalicylates alone. In people who cannot tolerate aminosalicylates, oral corticosteroids are recommended as they are also an effective treatment option.

The sequence of drugs recommended was more effective than starting with a high-dose oral aminosalicylate alone. There was some uncertainty around the cost effectiveness of this sequence. The data on the effectiveness of high-dose oral aminosalicylates combined with topical aminosalicylates was from an 8‑week clinical trial. The committee believed that in practice, people whose disease did not respond to treatment within 4 weeks would switch to another treatment. When the cost-effectiveness analysis allowed for early switching, the combination of a high-dose oral aminosalicylate and topical aminosalicylate was not cost effective. However, if it was assumed that everyone continued treatment as described in the trial, the combination of a high-dose oral aminosalicylate and topical aminosalicylate was more likely to be cost effective. The committee took the uncertainty about the cost-effectiveness results in the different scenarios into account in recommending the combination as first-line treatment.

There was some evidence on methotrexate for inducing remission, but it did not show a clear benefit, and there was no evidence on oral tacrolimus. To address these gaps in the evidence, the committee recommended further research on the effectiveness of tacrolimus and methotrexate.

All extents of disease

Most of the evidence was for adults. However, the committee agreed to generalise the recommendations to all people with a mild-to-moderate exacerbation or first presentation of ulcerative colitis.

There is limited evidence on oral corticosteroids. In addition, the committee agreed that the use of oral corticosteroids is generally reserved for later lines of treatment because of concerns about side effects. It is not clear which corticosteroid is most effective for each extent of disease. There is also limited evidence on immunomodulators, specifically oral tacrolimus and systemic methotrexate for each extent of disease. The committee recommended further research to address these uncertainties.

How the recommendations might affect practice

The new recommendations classify the extents of ulcerative colitis differently. This more closely reflects current practice, so will be clearer and more informative for people with mild-to-moderate ulcerative colitis and healthcare professionals.

The recommendations in the 2013 guideline referred to specific corticosteroids. To better reflect the available evidence, the updated recommendations refer to aminosalicylates and corticosteroids as a class rather than recommending individual treatments. This allows healthcare professionals and people with mild-to-moderate ulcerative colitis to choose the most appropriate corticosteroid or aminosalicylate, depending on patient preference, availability and acquisition cost.

The new recommendations specify that courses of oral corticosteroids should be time-limited. This should address varying practice in prescribing for some corticosteroids.

Full details of the evidence and the committee's discussion are in evidence review: induction of remission in mild-to-moderate ulcerative colitis.

  • National Institute for Health and Care Excellence (NICE)