Therapies for treating pain in ulcerative colitis

What is the aim of this review?

The aim of this Cochrane Review was to find out whether treatments for people with ulcerative colitis (UC) can improve pain.

We analysed data from five studies to answer this question.

Key messages

We cannot draw conclusions about any of these treatments for the management of pain in UC because of the very low certainty of the evidence.

It is unclear whether any of the therapies considered are better than each other, but there is limited evidence due to low numbers of studies and participants, and issues due to low certainty of the reporting of the research studies.

What was studied in the review?

People with ulcerative colitis commonly suffer pain, whether their disease is active on inactive.

Several types of therapies have tried to reduce pain in ulcerative colitis, including diets, psychological therapies, drugs, exercise therapies and brain therapies.

There is currently no agreement amongst clinicians as to which therapy is better.

What are the main results of the review?

We searched for randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) comparing any treatment with another or with a dummy/placebo treatment. We found five RCTs looking at 360 participants.

1) Authors reported improvement in pain for a relaxation training compared to no relaxation training, but we cannot draw conclusions about whether this is really the case because of the very low certainty of the evidence.

2) It is unclear whether there is any difference between any of the other therapies studied for the management of pain.

3) It is unclear whether any therapy leads to a difference in adverse events (minor or serious) when compared to any other therapy.

Conclusion

We have very low-certainty evidence for all interventions studied in this review on whether any of them can improve pain in people with ulcerative colitis. We have no confidence that these methods can actually improve pain in ulcerative colitis.

No conclusions can be drawn due to a lack of evidence, and quality issues with the studies that we found. Further research is needed, that addresses the certainty issues that we highlight.

How up-to-date is this review?

This review is up-to-date to April 2021.

Authors' conclusions: 

We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions.

While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn.

There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.

Read the full abstract...
Background: 

Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn’s disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC.

Objectives: 

To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis.

Search strategy: 

We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials.

Selection criteria: 

All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes.

Data collection and analysis: 

Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.

Main results: 

We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease.  

No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias.

One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported.

One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported.

One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported.

One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported.

One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported.

Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome.  We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence.

The reporting of secondary outcomes was inconsistent.

Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events.

Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes.