Oral budesonide therapy improves quality of life in patients with collagenous colitis
Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter.
Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life.
Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86–88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01).
Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.
KeywordsCollagenous colitis Budesonide Quality of life
Collagenous colitis is an idiopathic microscopic colitis characterised by chronic watery diarrhoea [1, 2]. The diagnosis of collagenous colitis is based upon histopathological examination of a biopsy specimen from colorectal mucosa, which usually appears macroscopically normal. The typical histological feature is a diffuse thickening of the subepithelial collagen layer beneath the basement membrane and an unspecific chronic inflammatory infiltrate of the lamina propria [3, 4]. However, collagenous colitis has a number of histological features normally associated with inflammatory bowel disease such as ulcerative colitis or Crohn’s disease . It has recently been shown that the mechanisms for diarrhoea in collagenous colitis include malabsorption due to defective transporters and the collagenous band, rheogenic anion secretion, and an impaired epithelial barrier with a passive back leak of ions and water into the intestinal lumen . Recent epidemiological studies suggest that in some populations the prevalence of collagenous colitis is higher than suggested in earlier studies [7, 8]. The impact of collagenous colitis on quality of life has hitherto not been investigated.
Budesonide is a locally acting, anti-inflammatory agent with low systemic activity because it is nearly 90% metabolised during its first pass through the liver to metabolites with minimal or no steroidal activity . It has recently been shown to be effective in treating collagenous colitis in three placebo-controlled trials [10, 11, 12]. As part of one of these trials, we investigated quality of life in patients with collagenous colitis and the effect of treatment with budesonide on quality of life.
Materials and methods
Study design and patients
Patients between 18 and 80 years of age with histologically confirmed collagenous colitis, and with at least five liquid or soft stools per day on average per week, were enrolled in a randomised, double-blind, placebo-controlled trial. The full methods and primary efficacy and safety results have been reported elsewhere . Major exclusion criteria included treatment with budesonide, salicylates, steroids, prokinetics, antibiotics, ketoconazole or non-steroidal anti-inflammatory drugs within the 4 weeks before randomisation, other endoscopically or histologically verified causes of diarrhoea, pregnancy or lactation, and previous colonic surgery.
The study was approved by the Ethics Committee of the University Hospital Dresden, Germany. Written informed consent was obtained from all patients prior to inclusion in the trial.
Eligible patients were randomised to receive three 3-mg controlled-release budesonide capsules (Entocort, AstraZeneca, Lund, Sweden) given once daily in the morning, or matching placebo. The treatment was given orally in a double-blind fashion for a period of 6 weeks. Concomitant use of loperamide was allowed for the first 4 weeks, but was not allowed for the last 2 weeks of the study. In cases of abdominal pain patients were allowed to use butylscopolamine.
Assessment of quality of life and symptoms
Quality of life was measured using the Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks of treatment. The GIQLI is a validated bilingual (German and English) questionnaire, which is applicable for benign and malignant diseases of the gastrointestinal tract [13, 14]. A good correlation between the GIQLI and other scores has been demonstrated [13, 14]. The GIQLI contains 36 items with a graded response, each ranging from 0 (worst) to 4 (best). The GIQLI score consists of four dimensions (symptoms, physical functioning, emotional functioning, social functioning) and ranges from 0 to 144. Healthy volunteers have been reported to have a mean score of 121–126 using the GIQLI [13, 14]. Clinical symptoms were assessed by standardised questionnaires before and after 6 weeks of treatment. Although these data have been reported previously, they are included here for completeness.
Assessment of compliance and adverse events
Compliance was assessed by pill count. Patients who took less than 80% of the prescribed pills were considered to be non-compliant and excluded from the analysis. Adverse events were assessed at the end of treatment. Spontaneous reports of adverse events were documented at the time of onset.
The chi-square test was used for mean comparisons, with p<0.05 indicating statistical significance. The quality of life analysis included only patients with complete assessment at baseline and at the end of treatment.
Fifty-one patients were enrolled in the placebo-controlled trial. There were no differences in demographic data between the budesonide and the placebo groups, as previously reported . Forty-five patients (11 men, mean age 60 years) were available for the per protocol analysis of clinical symptoms (budesonide: n=23; placebo: n=22). Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12).
Effect of budesonide on quality of life and symptoms
Quality of life measured by Gastrointestinal Quality of Life Index (GIQLI) before and after treatment with budesonide versus placebo
GIQLI score (mean ± SD)
After 6 weeks’ treatment
GIQLI dimension scores (mean ± SD)
After 6 weeks’ treatment
After 6 weeks’ treatment
After 6 weeks’ treatment
After 6 weeks’ treatment
A significantly larger number of patients in the budesonide group experienced improved stool consistency (n=20) compared with those in the placebo group (n=3; p<0.01). The median stool frequency per day decreased significantly in the budesonide group (from n=6 to n=2, p<0.01), but remained unchanged (n=5) in the placebo group. One patient in the budesonide group and two patients in the placebo group used loperamide during the first 4 weeks of the study according to the protocol. Butylscopolamine was not used during the entire study period.
Adverse events and compliance
One patient in the budesonide group (3.8%) and two patients in the placebo group (8.0%) discontinued the treatment prematurely due to lack of clinical response. Two patients in the budesonide group (7.7%) and one patient in the placebo group (4.0%) discontinued treatment prematurely due to adverse events. All other patients took the study medication as prescribed.
Collagenous colitis is an idiopathic chronic inflammatory bowel disease characterised by watery diarrhoea. The impact of collagenous colitis on quality of life was hitherto unknown. Our data show that quality of life is seriously decreased in patients with collagenous colitis and that budesonide treatment can improve quality of life in these patients.
Quality of life assessments are becoming increasingly important as a measure of the value of therapeutic treatments, particularly if definite therapeutic cure of the disease is not available. Therefore, the goals of clinical management should include both relief of symptoms and improvement of quality of life, particularly as symptoms do not necessarily correlate with quality of life. Previous studies have shown that quality of life is decreased in patients with inflammatory bowel disease and is improved significantly after treatment with budesonide or other immunosuppressive interventions [15, 16].
In the present study, the baseline GIQLI scores were low in both treatment groups (budesonide = 67, placebo = 86). These values compare with previously reported mean scores of 104 in patients with anal fissures , 94 in those with severe chronic constipation , 93 in those with faecal incontinence  and 87 in those with gastro-oesophageal reflux disease requiring surgery . Our study would suggest that collagenous colitis may be associated with a greater impact on quality of life than these other conditions. The GIQLI has, to date, generally been used to assess patient well being in conditions that require surgery. However, the questionnaire was developed as an instrument for evaluating quality of life in all gastrointestinal disorders and as such is valid for this study.
During the study, those patients treated with budesonide showed a significant improvement in their quality of life compared with those receiving placebo. This improvement was more pronounced in the dimension symptoms, followed by emotional functioning and physical functioning. No significant difference between the groups occurred in the dimension social functioning. A possible reason for this finding is that collagenous colitis does not have a strong impact on social functioning. We note that patients who received placebo generally had a higher quality of life at baseline than those in the budesonide group. The reason for this is unknown, but the result could imply a bias between the groups that potentially may have affected our results. However, analysis of individual changes show that large improvements in quality of life occurred in budesonide-treated patients who had relatively high or low GIQLI scores. Similarly, changes in the placebo-treated patients did not appear to be affected by baseline score. These individual data provide reassurance that the beneficial effect of budesonide is genuine, although a further investigation with patients matched for baseline quality of life would be of value.
Clearly, a limitation of this study is the relatively small number of patients for whom complete quality of life assessment was available, particularly in the placebo group (55% of the initial per protocol population). We speculate that patients who stopped treatment prematurely due to lack of efficacy, or those who experienced no improvement of symptoms at the end of treatment, may be more unwilling to perform post-treatment quality of life assessment. On the other hand, the fact that a larger proportion of patients in the budesonide group (74% of the initial per protocol population) were willing to perform post-treatment quality of life assessment may be a surrogate marker for a higher level of treatment satisfaction in the budesonide group. More extensive studies of quality of life in collagenous colitis and the effect of treatment on this parameter are in progress.
Budesonide is so far the only therapeutic intervention for which strong evidence of clinical and histological improvement in collagenous colitis exists [10, 11, 12]. Evidence suggests that budesonide treatment can result in a rapid response, with about 60% of patients achieving remission within 2 weeks . One randomised placebo-controlled study, to date only published in abstract form, has suggested a therapeutic benefit of bismuth subsalicylate . However, due to the small number of patients (n=9) enrolled in the trial, it is difficult to come to any definite conclusions about this therapeutic approach. Short-term prednisolone treatment does not appear to be particularly effective for collagenous colitis .
Based on all three fully published randomised trials [10, 11, 12], a recent Cochrane review calculated that the pooled odds ratio for clinical response to treatment with budesonide was 12.3 with a 95% confidence interval of 5.5–27.5, and two patients needing treatment, underlining the high efficacy of budesonide at inducing clinical remission in patients with collagenous colitis . However, it was further concluded that the long-term role of budesonide in the maintenance of remission or the treatment of relapses still needs to be defined.
Our study suggests that quality of life is seriously decreased in patients with collagenous colitis and to a greater extent than in a number of other gastrointestinal conditions such as severe chronic constipation and faecal incontinence. Treatment with oral budesonide capsules significantly improves quality of life and clinical symptoms in these patients.
The study was supported by AstraZeneca.
- 19.Miehlke S, Madisch A, Bästlein E et al (2003) Time to clinical remission in patients with collagenous colitis treated with budesonide capsules—results from a randomized, double-blind, placebo-controlled trial. Gut 52:A214Google Scholar
- 20.Fine K, Ogunji F, Lee E et al (1999) Randomized, double-blind placebo-controlled trial of bismuth subsalicylate for microscopic colitis. Gastroenterology 116:A880Google Scholar
- 22.Chande N, McDonald JW, MacDonald JK (2003) Interventions for treating collagenous colitis. Cochrane Database Syst Rev CD003575Google Scholar