Introduction Constipation-predominant irritable bowel syndrome (IBS-C) is a common and difficult disorder to manage. Linaclotide is licensed in the UK for symptomatic treatment of moderate to severe IBS-C. Data from randomised, controlled trials demonstrate that the drug improves symptoms in patients with IBS-C, but real-world data are lacking.
Methods We treated adult patients with IBS-C (Rome III Criteria), attending outpatient clinics in three UK hospitals, with linaclotide 290 mcg once daily. IBS symptoms were assessed at baseline, 4 weeks, and 12 weeks after commencing therapy using the validated IBS symptom severity scale (IBS-SSS). Responders were defined as those patients with a decrease in total IBS-SSS score of >75.
Results A total of 108 patients (mean age 43.2; range 17–84 years; 94 (87.0%) female) received linaclotide. In total, 4 week IBS-SSS scores were available for 72 (66.7%) patients, and 12 weeks scores in 26 (24.1%) patients. Effect of linaclotide on individual components of the IBS-SSS, as well as total IBS-SSS score, at 4 and 12 weeks are detailed in Table 1. There were 49 (45.4%) patients who responded to linaclotide, with a reduction in IBS-SSS of >75 at 4 weeks. The drug also led to a significant reduction in straining (3.9 at baseline vs. 2.0 at 4 weeks, P < 0.001), and increase in mean number of stools per week (3.8 at baseline vs. 8.9 at 4 weeks, P < 0.001). At 4 weeks, 61 (56.5%) patients continued the drug and 47 (43.5%) discontinued, 24 (22.2%) due to lack of efficacy or losses to follow-up, and 23 (21.3%) due to adverse events (AEs). Among the 61 patients continuing linaclotide, 22 (36.1%) were responders at 12 weeks. AEs occurred in 43 (39.8%) patients overall, which lead to discontinuation of the drug in 23 (21.3%) patients either before or at their 4 week assessment. These included diarrhoea in 28 (25.9%) (15 discontinued), abdominal pain in 6 (5.6%) (5 discontinued), nausea in 3 (2.8%) (1 discontinued), flatulence in 2 (1 discontinued), headaches in 2 (0 discontinued), faecal incontinence in 1 (1 discontinued), and urgency in 1 (0 discontinued).
Conclusion Linaclotide was effective in IBS-C patients in a real-world setting, with significant reductions in IBS-SSS scores and straining, and a significant increase in mean number of stools per week. Responder rates at 4 and 12 weeks were 45% and 36% respectively. 40% of patients reported AEs, with diarrhoea the commonest, occurring in 26% of patients. Previous literature has reported a lower frequency of AEs, which infrequently led to withdrawal of linaclotide. However, in our study the occurrence of AEs led to discontinuation in 21% of patients.
Disclosure of Interest None Declared