To compare the short-term efficacy and safety of linaclotide with macrogol 4000 powder and Maren pills in combination with otilonium bromide in the treatment of irritable bowel syndrome with constipation (IBS-C).

In this prospective, three-arm study, patients with IBS-C who met the criteria were enrolled in the outpatient clinic. On the basis of general treatment and health guidance, linaclotide (290 μg·d^-1) was orally administrated according to treatment preference and assigned to the treatment group; or macrogol 4000 powder (10 g·d^-1)+otilonium bromide (120 mg·d^-1), divided into the western medicine control group; or Maren pills (12 g·d^-1)+otilonium bromide (120 mg·d^-1), divided into the western and Chinese medicine control group. The efficacy endpoint was achieved in half or more of the course of treatment (≥2 weeks/4 weeks) with: at least 30% improvement in the degree of abdominal pain and at least 1 increase in complete spontaneous bowel movement (CSBM) per week compared to baseline. The general and baseline data of patients in the 3 groups were observed and compared, and changes in abdominal pain score (NRS), spontaneous bowel movement (SBM), CSBM, Bristol Stool Symptom Scale (BSFS), and IBS Symptom Severity Scale (IBS-SSS) were recorded. To evaluate drug-related adverse effects using univariate analysis and Logistic regression was used to analyze the influencing factors.

The number of valid cases that finally completed the study and were included in the statistical analysis was 129 (48 cases in the treatment group, 41 cases in the western medicine control group, and 40 cases in the western and Chinese medicine control group), and the three groups of patients were comparable overall. During the course of treatment, the improvement in abdominal pain, frequency of defecation, and degree of symptoms was better in the treatment group and the western and Chinese medicine control group than in the western medicine control group (both P<0.05). At the end of the 4th week, 89.58% (43/48) of the treatment group and 90% (36/40) of the western and Chinese medicine control group reached the efficacy endpoint, both of which were higher than 73.17% (30/41) of the western medicine control group (both P<0.05). Univariate analysis showed that baseline abdominal pain NRS and IBS-SSS were influential factors for clinical efficacy outcome (both P<0.05). Covariate diagnostic validation followed by binary logistic regression analysis suggested linaclotide (P=0.023), baseline abdominal pain NRS (P=0.009) and baseline IBS-SSS (P=0.000) were independent influences on clinical efficacy. Related adverse effects, the main ones in the treatment group were diarrhea (16.67%), tenesmus (6.25%), and abdominal distension (4.17%), etc. Only the incidence of diarrhea was higher than that in the western and Chinese medicine control group (16.67% vs 2.5%, P<0.05), and there was no significant difference in the risk of other adverse effects.

The short-term clinical efficacy and safety of linaclotide in IBS-C patients are good, and it has the characteristics and advantages of "one drug with two effects". So it's worthy of further promotion and application.