title: Impact of linaclotide treatment on work productivity and activity impairment in adults with irritable bowel syndrome with constipation: results from 2 randomized, double-blind, placebo-controlled phase 3 trials.
abstract: BACKGROUND
  Irritable bowel syndrome with constipation (IBS-C), a chronic functional gastrointestinal disorder, has been shown to negatively affect work productivity and impair daily activity, resulting in a substantial burden for patients and employers. Linaclotide is a first-in-class guanylate cyclase-C agonist approved for the treatment of adults with IBS-C and chronic idiopathic constipation in the United States.
  
  
  OBJECTIVE
  To analyze the impact of treatment with linaclotide on work productivity and daily activity impairment in adults with IBS-C and estimate the indirect costs associated with this condition.
  
  
  METHODS
  This was a post-hoc analysis of data on IBS-C-related work time missed and work and activity impairment from 2 phase 3 clinical trials that assessed the efficacy and safety of linaclotide therapy in adults with IBS-C. The Work Productivity and Activity Impairment Questionnaire for IBS-C (WPAI:IBS-C) was self-administered at baseline and at weeks 4, 8, and 12 during the 12-week treatment periods in Trials 1 and 2 and at weeks 16, 20, and 26 during the extended treatment period in Trial 2. An analysis of covariance was conducted to assess changes from baseline to all study weeks for each WPAI:IBS-C measure. Indirect costs were calculated by converting overall work productivity losses into monetary values using the human capital cost approach.
  
  
  RESULTS
  Of the 1602 patients with IBS-C who were randomized in the 2 clinical trials, 1555 (97.1%) completed a baseline and at least 1 postbaseline WPAI:IBS-C assessment and were included in the analysis cohort; 1148 (71.7%) of these patients were employed. Once-daily treatment with linaclotide significantly reduced overall work productivity loss and daily activity impairment among patients with IBS-C at all study weeks. From baseline to week 12, compared with placebo, linaclotide significantly reduced presenteeism by 5.2%, overall work productivity loss by 6.1%, and daily activity impairment by 4.7% (all P <.01) and led to a numerically greater decrease in absenteeism. From baseline to week 26, compared with placebo, reductions with linaclotide were 5.9% for presenteeism, 7.5% for overall work productivity loss, and 6.7% for daily activity impairment (all P <.05). Reductions in overall work productivity loss from baseline to week 26 translate to 103 hours to 156 hours annually and correspond to an avoided overall work loss of $3209 to $4861 annually for an employee with IBS-C.
  
  
  CONCLUSIONS
  The results of this analysis indicate that appropriate treatment of IBS-C with medications such as linaclotide can reduce work-related impairment associated with IBS-C. In addition, IBS-C therapies that effectively manage this chronic condition and improve employees' quality of life and work productivity may represent significant cost-savings for employers in the form of avoided work productivity losses.
authors.affiliation: Manager, Health Economics and Outcomes Research, Forest Research Institute, LLC, a subsidiary of Actavis plc, Jersey City, NJ.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Buono
authors.affiliation: Director, Biostatistics, Forest Research Institute, LLC, a subsidiary of Actavis plc, Jersey City, NJ.
authors.forename: Stavros
authors.initials: S
authors.lastname: Tourkodimitris
authors.affiliation: Senior Director, Health Economics and Outcomes Research, Ironwood Pharmaceuticals, Cambridge, MA, during this study.
authors.forename: Phil
authors.initials: P
authors.lastname: Sarocco
authors.affiliation: Senior Principal Clinical Scientist, Clinical Affairs, Ironwood Pharmaceuticals, Cambridge, MA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Johnston
authors.affiliation: Director, Health Economics and Outcomes Research, Forest Research Institute, LLC, a subsidiary of Actavis plc, Jersey City, NJ.
authors.forename: Robyn T
authors.initials: RT
authors.lastname: Carson