Introduction Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that fluctuate over time. It is important that symptom control with pharmacological therapy can be re-established if treatment is re-introduced after a period of discontinuation. Linaclotide (Constella®; LIN), a first-in-class, minimally absorbed, guanylate cyclase-C agonist for the treatment of adults with IBS with constipation (IBS-C), has been investigated in a pivotal Phase 3 trial (Trial 31) that included a 4-week post-treatment randomised withdrawal period (RWP). This post-hoc analysis examined the impact on treatment satisfaction of re-introducing LIN after the RWP.
Method Patients (pts) who were randomised to LIN 290 μg once daily in the 12-week treatment period in Trial 31 were subsequently re-randomised to LIN (LIN-LIN; n = 158) or placebo (LIN-PBO; n = 154) in the 4-week RWP. Eligible pts could then receive LIN for a further 78 weeks in an open-label long-term study (LTS). Pt-reported treatment satisfaction was assessed at study visits during Weeks 2, 4, 8, 12, 14 and 16 of Trial 31, and 2, 6, 14, 26, 39, 52, 65 and 78 of the LTS. Pts rated their satisfaction with the ability of the study medication to relieve their IBS symptoms on a 1–5 point scale (1 = not at all satisfied, 2 = a little satisfied, 3 = moderately satisfied, 4 = quite satisfied, 5 = very satisfied). Data were analysed using a last observation carried forward approach.
Results At the end of the 12-week treatment period in Trial 31, treatment satisfaction was similar for LIN pts who were re-randomised to PBO and pts who remained on LIN (mean [standard error of the mean, SEM] treatment satisfaction: 3.42 [0.12] vs 3.37 [0.12]). During the 4-week RWP, pts re-randomised to PBO (LIN-PBO) showed a significant (P < 0.05) mean reduction in treatment satisfaction compared with pts who remained on LIN (LIN-LIN). At the end of the RWP, the mean (SEM) treatment satisfaction in the LIN-PBO group was 3.18 (0.12) vs 3.47 (0.12) in the LIN-LIN group. After re-introduction of LIN in the LTS, mean (SEM) treatment satisfaction increased to previous levels in the LIN-PBO group within 2 weeks (LIN-PBO, 3.69 [0.11] vs LIN-LIN, 3.70 [0.09]). Treatment satisfaction was sustained to the end of the 78-week LTS (LIN-PBO, 3.93 [0.12] vs LIN-LIN, 3.81 [0.10]). Similar to the Phase 3 trials, the most common adverse event observed during the LTS among LIN-treated pts was diarrhoea.
Conclusion Pts with IBS-C who discontinued LIN therapy for a 4-week period experienced a significant reduction in treatment satisfaction. Subsequent re-introduction of LIN resulted in similar high levels of treatment satisfaction compared with pts who remained on long-term LIN therapy.
Disclosure of interest C. Díaz Employee of: Almirall S. A., M. Falques Employee of: Almirall S. A., D. Vilardell Employee of: Almirall S. A., J. Fortea Employee of: Almirall S. A., S. Shiff Employee of: Forest Laboratories, J. Johnston Employee of: Ironwood Pharmaceuticals.