Linaclotide for the treatment of patients with IBS-C and FC in clinical practice in Mexico

BACKGROUND: Linaclotide (LIN) is a guanylatecyclase-C agonist approved for the treatment of irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC) in several countries. Efficacy is reported high compared to placebo, and tolerability varies among different populations. For example, diarrhea and drug discontinuation ranges from 9.6% and 0.7% in China to 26% and 21% in UK. In LatinAmerica, there is no information regarding efficacy and tolerability with LIN. AIM: To assess LIN-associated symptomatic improvement, as well as side effects in the treatment of IBS-C and FC in routine clinical practice in Mexico. METHOD: We assessed symptom improvement and side effects of LIN 290 mcg in adult patients with IBS-C or FC (Rome III criteria) whom received the drug in 6 different outpatient clinics in Mexico. LIN was prescribed by gastroenterologist's experts in the treatment of functional GI disorders. Symptom improvement was assessed using a 4 point Likert scale after 4 and 12 weeks of treatment (0=worst, 1=no improvement, 2=<50% compared to baseline, 3=>50% compared to baseline, 4=no symptoms). Diarrhea, as the main adverse effect, was evaluated from the first dose of LIN and its severity was assessed using a 4 point Likert scale during the first week (0=none, 1=Mild, 2=moderate,3= severe). RESULTS: A total of 142 patients (mean age 45; range 17-85 years; 120 (85.0%) female) were included. Ninety four (66%) had IBS-C and 48 (34%) FC. Mean duration of symptoms before treatment was 8.7 yrs. (0.5-30). Mean bowel movements per week was 2.5 (range from 1 to 6). 56% of IBS-C had moderate to severe symptoms before treatment. Overall, 62 patients (44%) had loose stools after the first LIN dose. First loose stool appearead after 7.3 hours after first dose (range 1-120 hours). Mean number of bowel movements on day 1 was 3.4 (0-12). Mean duration of diarrhea was 4.5 days (0-30). Diarrhea was considered mild in 56% of cases, moderate in 25% and severe in 18%. However, discontinuation of treatment due to diarrhea occurred only in 15 cases (10.6%). Among 118 subjects that were evaluated at week 4, 72% (n=85) reported improvement >50% or no symptoms compared to baseline. At week 12, improvement >50% or absence of symptoms was reported in 81% of patients (n=88).Discontinuation due to diarrhea was not related to gender, age, duration of symptoms, indication (IBS-C or FC) or age (p>0.05). However, subjects who suspended LIN had more bowel movements per week at baseline (4.1 vs 2.4, p=0.01) CONCLUSIONS: LIN is an effective treatment for IBS-C and FC Mexican patients. Most of the patients (81%) reported improvement at week 12. Mild diarrhea occurs in 44% of patients during the first 5 days of treatment, however discontinuation rates was 10.6%, similar to those reported in other countries.