Linaclotide and Sexual Subscale Scores on IBS-QOL

August 15, 2013

Tori Socha

Orlando—Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that may result in diminished quality of life (QOL) and psychosocial well being. In addition, patients with IBS may experience decreased sexual desire and activity.

Two previous phase 3 trials have shown a significant increase in abdominal and bowel symptoms in patients who received linaclotide (LIN) compared with patients who received placebo. LIN is a minimally absorbed guanylate cyclase-C agonist that is FDA-approved for treatment of IBS with constipation (IBS-C).

Both of the trials utilized the IBS-QOL, a self-reported, IBS-specific QOL measure that includes a sexual subscale. Researchers recently conducted an analysis to determine whether IBS-QOL sexual subscale scores improved with treatment with LIN compared with placebo in patients with IBS-C who indicated at baseline that their bowel problems had an impact on sexual desire and activity.

The researchers reported results of the analysis during a poster session at DDW. The poster was titled The Effect of Linaclotide on IBS-QOL Sexual Subscale Scores in Patients with Irritable Bowel Syndrome with Constipation: Results from a Post Hoc Analysis of Two Phase 3 Trials of Linaclotide.

The sexual subscale includes 2 measurements: (1) sexual activity difficulty (“Because of my bowel problems, sexual activity is difficult for me”) and (2) reduced sexual desire (“My bowel problems reduce my sexual drive”). Patients rated both items on a 5-point scale, with 1 indicating “not at all” and 5 indicating “extremely/a great deal.” The total sexual subscale score is the sum of the 2 items inversely scaled to 0-100; higher scores indicate better QOL.

The post hoc analysis evaluated the intent-to-treat (ITT) population and the impaired sexuality subgroup (patients with sexual subscale scores ≤50). At week 12, sexual subscale scores of LIN patients were compared with those of patients receiving placebo.

Most of the patients in the IBS-C trials were female (90%). Of the 1598 ITT patients with a sexual subscale score, 33% (n=522) had a score ≤50 and 31% (n=498) had a score of 100. Treatment with LIN was associated with significantly improved change-from-baseline sexual subscale scores at week 12 compared with placebo in both the ITT population and the impaired sexuality subgroup (P<.001 for both populations).

In a comparison of males versus females, although baseline scores were higher (better) for men, the improvements versus placebo noted in the ITT population were similar. For the impaired sexuality subgroup, the improvements were greater for men than for women. However, the researchers noted that the sample size for men was too small to establish the significance of the results.

In summary, the researchers said, “In the phase 3 IBS-C trials, 33% of IBS-C patients had IBS-QOL sexual subscale scores ≤50 at baseline, indicating IBS symptoms significantly affected their sexual activity and desire. More female patients than male patients had baseline sexuality impairment. Overall, patients in two phase 3 IBS-C trials demonstrated a statistically significant improvement in overall QOL, as well as sexual subscale score, based on the IBS-QOL, comparing patients receiving linaclotide with those receiving placebo.”

They concluded by noting that, “These results indicate that linaclotide treatment improves IBS-QOL sexual subscale scores in female and male IBS-C patients compared with placebo in the overall population and a subpopulation of patients with impaired sexuality at baseline.”

This study was supported by Forest Laboratories, Inc. and Ironwood Pharmaceuticals, Inc.