Introduction Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to relieve constipation and improve abdominal pain and discomfort in patients with irritable bowel syndrome with constipation (IBS-C), but there are limited UK-specific real-world data to support this.
Method A multi-centre, observational, prospective 52 week study was conducted in 8 specialist hospitals in England and Scotland, with the primary objective to describe the change in IBS-Symptom Severity Scale (IBS-SSS) score from baseline at 12 weeks after linaclotide initiation. Consenting patients aged ≥18 years initiated on linaclotide (290 mcg) for IBS-C were recruited. Data on patient demographic and clinical characteristics, concomitant medications, patient-reported outcomes (including IBS-SSS) and adverse events (AEs) were collected. Results at 12 weeks (primary endpoint) have been presented previously; here we report analysis of real-world clinical experience 52 weeks post-linaclotide initiation.
Results 202 patients were recruited; 185 (92%) female. At baseline, median age was 44.9 (range 18–77) years; 84 (42%) reported concomitant laxative use. Mean baseline IBS-SSS score was 339 (SD ±92; n=193); 129 (67%) patients had IBS-C classified as severe (score ≥300), 54 (28%) moderate (175<300), 9 (5%) mild (75<175) and 1 (0.5%) in remission (<75). At 52 weeks, mean IBS-SSS was 256 (SD ±116; n=78); 31 (40%) patients with severe IBS-C, 27 (35%) moderate, 14 (18%) mild, 6 (8%) in remission. IBS-SSS scores improved significantly between baseline and 52 weeks, with a mean decrease of 71 (SD ±106) points overall (t-test p<0.001, n=76 with paired data; Figure 1); 94 (SD ±102) points in the patients remaining on linaclotide (n=34, p<0.001). 41 (54%) of the 76 patients with paired data reported responding to treatment (i.e. reduction in IBS-SSS of ≥50 points, OR score fell below 150 [if baseline score ≥150]). At 52 weeks, 41 (20%, n=202) patients remained on linaclotide, 87 (43%) had stopped (<4 doses in last week), most commonly due to side effects [n=51] or lack of efficacy [n=18]), 3 (1.5%) were lost to follow up and 71 (35%) not known. Overall, 174 AEs possibly related to linaclotide were reported in 77 (38%) patients, most commonly diarrhoea (n=51, 25%), abdominal pain (n=18, 9%) and abdominal distension (n=13, 6%).
Conclusion Linaclotide was associated with a significant improvement in IBS-SSS score at 52 weeks and was reasonably well tolerated. These results provide valuable insights into the longer-term outcomes of linaclotide treatment in patients with IBS-C in real-world clinical practice.
Disclosure of Interest A. Emmanuel Conflict with: Has acted on advisory boards for Allergan, J. McLaughlin: None Declared, Y. Yiannakou Conflict with: Has received an educational grant from Allergan, Conflict with: Has received advisory board fees from Allergan, Conflict with: Has received speaker fees from Allergan, S. McLain-Smith Conflict with: Employee of pH Associates, which was commissioned by Allergan to provide support with research design, conduct, analysis and scientific editorial services
- irritable bowel syndrome