Introduction
Up to 30% of the under 18 years age group suffer from functional constipation with significant impact on health-related quality of life. In addition to lifestyle and dietary modifications, the currently available medication (e.g. polyethylene glycol, lactulose, stimulant laxatives) have low response rates, frequent side-effects, and non-sustained effects. Lubiprostone is an oral chloride channel-2 activator that stimulates gastrointestinal fluid secretion, softens stools, and facilitates bowel movements. It is approved in the United States for the treatment of chronic idiopathic constipation in adults. The evidence about the effectiveness and safety of lubiprostone in pediatric age group is still limited, representing a gap in clinical practice.
Aims & Methods
Aim: To evaluation of the effectiveness and safety of lubiprostone in children and adolescents with functional constipation.
Patients and Methods: In an open label, randomized, controlled trial, we included 277 patients in the age group 8-18 years diagnosed as functional constipation (FC). The diagnosis of FC was dependent on ROME IV criteria. After physical evaluation, patients were randomly (Simple randomization) assigned to one of 2 arms. First arm (n =137): patients received lubiprostone at doses of 24 mcg/day on divided doses or 24 mcg BID if weighing < 50 kg or ≥ 50 kg, respectively. Second arm (control, n = 140): patients received Bisacodyl, lactulose, or Sodium Picosulfate in appropriate doses. Treatment extended for 12 weeks followed by 4 weeks follow-up after treatment cessation (week 16). Evaluation during the study was done at baseline, weeks 2, 8, 12, and 16 of the study. The primary endpoint was spontaneous bowel movements (SBM) at week 12 and 16 compared to baseline. Improvement in the constipation was defined as increased SBM ≥ 1 SBM/week in frequency compared with baseline and maintaining ≥ 3 SBMs/week for at least 8 weeks (including the last 4 study weeks and the 4 weeks of follow-up). Safety assessment was done at clinic visits and by telephone as well as recording of patient-reported AEs.
Results
The two arms were matched as regards the mean ± SD of SBM at baseline (1.23 ± 0.37 motions/week for lubiprostone vs. 1.19 ± 0.28 motions/ week for control, P = 0.24). the primary endpoint was achieved in 128 (93.4%) patients of lubiprostone group, and in 48 (34.3%) patients of the control group (p < 0.001, ꭓ2 = 105.42). In subgroup analysis, lubiprostone was superior to different laxatives in the control arm (p< 0.001, F = 95.6). At 12 weeks, the mean SMB in lubiprostone arm was (4.78 ± 0.99 motion/week) vs. (2.70 ± 1.04 /week) for control group (P <0.001). This difference was sustained for 4 weeks follow-up in lubiprostone group only. The overall side-effects occurred among 46% of lubiprostone group, and 48% in control group (p = 0.99). The most common adverse event in lubiprostone group were colicky abdominal pain (26%), and headache (14%), There was no life-threatening drug-related adverse events.
| Lubiprostone, n = 137 | control, n = 140 | P |
Spontaneous bowel motion baseline
| 1.23 ± 0.37
| 1.19 ± 0.28
| 0.24 |
Spontaneous bowel motion 2 weeks
| 3.05 ± 0.94
| 2.64 ± 1.58
| 0.008 |
Spontaneous bowel motion 8 weeks
| 4.24 ± 0.97
| 2.97 ± 1.32
| < 0.001 |
Spontaneous bowel motion 12 weeks
| 4.78 ± 0.99 | 2.70 ± 1.04
| < 0.001
|
Spontaneous bowel motion 16 weeks
| 4.73 ± 1.14 | 2.25 ± 1.01
| < 0.001
|
Conclusion
Lubiprostone is superior to conventional laxatives, and well tolerated treatment for functional constipation in pediatric and adolescent age groups.
References
van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroentero 2006;101:2401–9.
Hyams, J. S., Di Lorenzo, C., Saps, M., Shulman, R. J., Staiano, A., & van Tilburg, M. Childhood Functional Gastrointestinal Disorders: Child/Adolescent. Gastroenterology 2016; 150(6), 1456–1468.e2.
Levy EI, Lemmens R, Vandenplas Y, Devreker T. Functional constipation in children: challenges and solutions. Pediatric Health Med Ther. 2017 Mar 9;8:19-27. doi: 10.2147/PHMT.S110940.
Benninga, M. A., Hussain, S. Z., Sood, M. R., Nurko, S., Hyman, P., Clifford, R. A., et al. Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2022; 20(3), 602–610.e5.
Disclosure
Nothing to declare
