Irritable bowel syndrome with constipation: a European-focused systematic literature review of disease burden

Figures & data

Figure 1.  Number of articles proceeding at each stage of the systematic review. IBS-C, irritable bowel syndrome with constipation.

Table 1.  Total number (%) of studies reporting data for different IBS-C topics.*

IBS-C topic	Number (%) of studies
Treatment	42 (38%)
Definition/aetiology/diagnosis	36 (32%)
Humanistic burden	18 (16%)
Burden of illness	8 (7%)
Economic burden	8 (7%)

*Total number of studies is >106, as some publications report data for multiple IBS-C topics.

IBS-C, irritable bowel syndrome with constipation.

Table 2.  Summary of humanistic studies using the IBS-QOL to evaluate HRQoL in patients with IBS-C.

Authors (year)	Study design and patients	Intervention	HRQoL outcomes	Conclusion
Amouretti et al.61 (2006)	Prospective survey study of QoL in French patients (n = 253, mean age 48.3 years, 76% female) with IBS. Sample included: 26% IBS-C, 28% IBS-D, and 46% IBS-A.	None	Women had significantly poorer HRQoL than men in all IBS-QOL domains except sleep.	IBS has a significant impact on patient HRQoL. Specific characteristics (gender, symptom severity, and time since onset of symptoms) were predictive of greater HRQoL impairment.
Cain et al.62 (2006)	Secondary analysis of three studies (conducted between 1997 and 2004) evaluating the impact of IBS on QoL in women (n = 242, mean age 33 years) with IBS. Sample included: 26% IBS-C, 37% IBS-D, and 34% IBS-A.	None	Most frequent symptom: intestinal gas (on 74% of days, with moderate/worse severity 27% of days). Abdominal pain was most strongly related to IBS-QOL score and diary-reported life-impact variables, including interference with relationship, work, and other plans. Correlations of IBS symptoms with life-impact variables did not differ significantly in IBS sub-groups.	While intestinal gas was the most frequent symptom, abdominal pain was the most disruptive symptom with the largest impact on QoL. Agents that effectively treat IBS symptoms will likely impact QoL.
Drossman et al.64 (2009)	Pooled analysis of efficacy/safety from two phase III, 12-week RCTs of lubiprostone. IBS-QOL outcomes were evaluated at baseline, week 4 and week 12. Adults (n = 1171, mean age 46.6 years) with IBS-C.	Lubiprostone 8 μg daily vs placebo	Overall analysis of IBS-QOL scores indicated a trend towards greater improvement with lubiprostone at week 12 (p = 0.066). Sub-domains of ‘body image’ and ‘health worry’ were significantly improved in the lubiprostone group at week 12 compared with baseline (p ≤ 0.025). Clinically meaningful changes (>14 points) in IBS-QOL domains of social reaction, food avoidance, health worry, body image, and dysphoria were observed in the lubiprostone group.	Lubiprostone was associated with a trend towards improved QoL. Significant improvements were observed in ‘body image’ and ‘health worry’ sub-domains compared with placebo.
Hawkes et al.68 (2002)	8-week RCT for the safety/efficacy of naloxone in IBS-C. Adults (n = 28 [22 females], mean age 45.4 years) with IBS-C or IBS-A.	Naloxone 20 mg daily vs placebo	At baseline, mean QoL scores were lower in the placebo group than in the treatment group. Scores for sleep and sexual domains were significantly lower (p = 0.05 and p = 0.03, respectively). During the study, there were trends of improvement across all but one domain in both placebo and treatment groups. Naloxone improved all nine QoL domains from baseline, with greater improvement than placebo in emotional, mental health, energy, physical functioning, food, social role, and physical role.	Naloxone is well tolerated and beneficial in patients with IBS-C, although larger clinical trials are needed to provide sufficient statistical power to assess efficacy.
Johanson et al.69 (2008)	3-month, multi-centre RCT evaluating the safety/efficacy of lubiprostone. Changes in QoL were assessed (secondary end-point) at weeks 4 and 12. Adults (n = 195, age range 18–80 years, 90% female) with IBS-C.	Lubiprostone 16 µg, 32 µg, or 48 µg daily vs placebo	No significant trend in QoL related to lubiprostone. The sub-domain ‘health worry’ score showed significant increase from baseline at week 4 (baseline placebo value was 45.3 and lubiprostone value range was 37.7–44.4; week 4 values were placebo 53.7 and lubiprostone 59.5–66.4, p = 0.021) and week 12 (placebo 58.5 and lubiprostone 61.5–66.1, p = 0.041). Patients receiving lubiprostone 48 µg reported significant improvements in ‘health worry’ at 4 and 12 weeks from baseline (p = 0.004 and p = 0.021, respectively).	Lubiprostone may impact QoL in patients with IBS-C; however, further trials are necessary.
Johnston et al.70 (2010)	12-week, multicentre RCT evaluating efficacy/safety of linaclotide. Adults (n = 420, mean age 44.4 years, 92% female) with IBS-C.	Linaclotide 75, 150, 300, or 600 μg daily vs placebo	Differences in IBS-QOL at 12 weeks were not significant from placebo for any dose, but IBS-QOL scores showed clinically meaningful (≥14-point) improvement in more than one-third of patients in all treatment groups. Specifically, 37% of patients treated with linaclotide had a change from baseline in overall IBS-QOL score of ≥14 points. Linaclotide 300 μg and 600 μg significantly improved the IBS-SSS QoL item (p < 0.01 and p < 0.05 vs placebo, respectively).	Some improvements in QoL were observed for all linaclotide treatment groups, although differences in overall scores from baseline were not significant. These, along with clinical findings, support the effect of linaclotide in IBS-C.
Lembo et al.71 (2010)	12-week multi-centre RCT evaluating efficacy/safety of renzapride in women with IBS-C. Adult females (n = 1798, mean age 43.3 years).	Renzapride 4 mg once daily or 2 mg twice daily vs placebo	A modest improvement in IBS-QOL was observed in all three groups. No significant differences were present in the IBS-QOL sub-scales.	Given a limited increase in efficacy vs placebo and the incidence of ischaemic colitis, data suggest that the benefit:risk ratio of renzapride is insufficient to warrant further study in IBS-C.
Tack et al.77 (2005)	RCT evaluating safety/efficacy of tegaserod for IBS-C. Patients received treatment for 1 month; those showing full/partial response entered a treatment-free period. Upon symptom recurrence patients were retreated for another month. Adult females (n = 2660, age range 17–66 years) with IBS-C. Of 2135 patients (525 placebo) in the first treatment period, 1194 (250 placebo) entered the second treatment period.	Tegaserod 6 mg daily vs placebo	Tegaserod significantly improved QoL compared to placebo in the first treatment period (4 weeks) (p < 0.05).	Clinical benefits of tegaserod were associated with improvement in QoL and high satisfaction. Tegaserod may be useful for short term, repeated treatment in females with IBS-C.

HRQoL, health-related quality-of-life; IBS, irritable bowel syndrome; IBS-A, irritable bowel syndrome alternating; IBS-C, irritable bowel syndrome with constipation; IBS-D, irritable bowel syndrome with diarrhoea; IBS-QOL, Irritable Bowel Syndrome Quality-of-Life instrument; IBS-SSS, Irritable Bowel Syndrome Symptom Severity Scale; QoL, quality-of-life; RCT, randomized controlled trial.

Table 3.  Studies evaluating economic burden associated with IBS-C.

Authors (year)	Study design	Treatment	Population	Outcomes
Reilly et al.15 (2005)	Analysis of data from an international, multi-centre RCT evaluating the efficacy/safety of tegaserod in women with IBS-C77. Work-related productivity and daily activity were assessed with the WPAI:IBS-C at weeks 2 and 4.	Tegaserod 6 mg twice daily vs placebo	Adult females with IBS-C (n = 2660) were randomized to receive tegaserod or placebo. Among all randomized patients, 1675 were employed (tegaserod [n = 1363], placebo [n = 312]) and completed the WPAI:IBS-C.	Overall, in employed women, tegaserod significantly reduced work and daily activity impairment at weeks 2 and 4 vs placebo. At week 4 tegaserod reduced absenteeism by 2.6% (p = 0.004), presenteeism by 5.4% (p < 0.0001), overall work productivity loss by 6.3% (p < 0.0001), and activity impairment by 5.8% (p < 0.0001) compared with baseline. In European countries, tegaserod only significantly reduced daily activity impairment at week 2 compared with placebo (p = 0.04). At week 4, tegaserod significantly reduced all work impairment measures, including absenteeism (p = 0.04), presenteeism (p = 0.05), overall work productivity loss (p < 0.003), and activity impairment (p = 0.004) compared with baseline. Conclusion: Tegaserod improves work and daily activity function in patients with IBS-C.
Tack et al.77 (2005)	Multi-centre prospective, randomized, double-blind, placebo-controlled, parallel-group study for the safety/efficacy of tegaserod in women with IBS-C. Work productivity was assessed using the WPAI:IBS-C at baseline and 2 weeks during both treatment periods.	Tegaserod 6 mg twice daily vs placebo	Adult females with IBS-C (n = 2660) were randomized to treatment for 1 month, and those showing full or partial response entered a treatment-free period. If symptoms recurred, patients were re-treated for another month. First treatment period: tegaserod (n = 1610), placebo (n = 525); second treatment period: tegaserod (n = 944), placebo (n = 250).	Patients treated with tegaserod had significantly improved WPAI:IBS-C scores vs placebo during the first treatment period (p < 0.05); significantly less presenteeism, less work impairment (presenteeism and absenteeism), and less activity impairment (all p < 0.05). Conclusion: Tegaserod may be associated with positive effects on work productivity in women with IBS-C.

IBS-C, irritable bowel syndrome with constipation; RCT, randomized controlled trial; WPAI:IBS-C, Work Productivity Activity Impairment for irritable bowel syndrome with constipation.

Figure 2.  Summary of treatment guideline recommendations for the management of IBS-C. ‘Alarm’ symptoms, symptoms that may suggest organic disease; BSG, British Society of Gastroenterology; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; FBC, full blood count; IBS-C, irritable bowel syndrome with constipation; NICE, National Institute for Health and Clinical Excellence; WGO, World Gastroenterology Organisation.

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Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a Phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology 2010;139:1877-86

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