Z Gastroenterol 2018; 56(07): 738-744
DOI: 10.1055/s-0043-124875
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in a real‑world setting – results from a German noninterventional study

Wirksamkeit und Verträglichkeit von Linaclotid bei der Behandlung des Obstipations-prädominanten Reizdarmsyndroms – Ergebnisse einer nicht-interventionellen Studie in Deutschland
Viola Andresen
1   Israelitisches Krankenhaus, Hamburg, Germany
,
Stephan Miehlke
2   Facharztzentrum Eppendorf, Hamburg, Germany
,
Elmar Beck
3   Anfomed, Möhrendorf, Germany
,
Gwen Wiseman
4   Former employee of Allergan plc, Marlow, United Kingdom
,
Peter Layer
1   Israelitisches Krankenhaus, Hamburg, Germany
› Author Affiliations
Further Information

Publication History

15 September 2017

11 December 2017

Publication Date:
09 May 2018 (online)

Abstract

Background Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist approved for the treatment of irritable bowel syndrome with constipation (IBS-C). This study assessed the efficacy and tolerability of linaclotide in IBS-C in routine clinical practice in Germany.

Methods This was a 52-week, noninterventional study of linaclotide in patients aged ≥ 18 years with moderate to severe IBS-C. Severity of abdominal pain and bloating and frequency of bowel movements were assessed over 5 study visits. Treatment-related adverse events were recorded.

Results The study enrolled 375 patients; the mean observation duration was 4.4 months. Linaclotide marketing was halted during the study period for economic reasons, accounting for low patient numbers and short observation duration. Linaclotide significantly reduced mean (standard deviation [SD]) scores between treatment start (visit 1) and study end (visit 5) for abdominal pain intensity (visit 1: 4.87 [2.63] vs. visit 5: 2.40 [2.20], p < 0.0001), mean [SD] bloating intensity (visit 1: 5.30 [2.70] vs. visit 5: 2.86 [2.34], p < 0.0001), and increased mean [SD] bowel movement frequency (visit 1: 2.71 [1.80] vs. 4.38 [1.86], p < 0.0001). Diarrhea, occurring in 5.1 % of patients, was the most common adverse event.

Conclusion Linaclotide is effective in improving the major symptoms of IBS-C and demonstrates a favorable safety profile in the real-world environment of routine clinical practice. DRKS (www.drks.de/): DRKS00005088.

Zusammenfassung

Einleitung Linaclotid ist ein nur minimal absorbierbarer Guanylatcyclase-C-Agonist, der für die Behandlung des Obstipations-prädominanten Reizdarmsyndroms (IBS-C) zugelassen ist. Es war das Ziel der vorliegenden Studie, Wirksamkeit und Verträglichkeit von Linaclotid in der praktischen Routineanwendung in Deutschland zu untersuchen.

Methodik In einer nicht-interventionellen Studie wurden die Effekte einer Linaclotid-Medikation bei Patienten (≥ 18 Jahre) mit mäßiggradig bis schwer ausgeprägtem IBS-C bei einem 52-Wochen Zeitraum analysiert. An 5 sequentiellen Studienvisiten wurden die Schwere von Bauchschmerzen und Blähungen, die Stuhlfrequenz und therapiebedingte Nebenwirkungen dokumentiert.

Ergebnisse Die Studie wurde an 375 prospektiv eingeschlossenen Patienten über eine mittlere Beobachtungsdauer von 4,4 Monaten durchgeführt. Da während der Studienperiode die Vermarktung von Linaclotid aus wirtschaftlichen Gründen beendet wurde, konnten weder die vorgesehenen Fallzahlen noch die geplante Beobachtungsdauer realisiert werden. Die Einnahme von Linaclotid war mit einer signifikanten Abnahme der abdominalen Beschwerden sowie einer Zunahme der Stuhlfrequenz (jeweils Mittelwerte [Standardabweichung]) assoziiert: zwischen Visite 1 (vor Behandlungsbeginn) und Visite 5 (gegen Ende der Behandlungsperiode) veränderten sich die abdominalen Schmerzscores von 4,9 [2,6] auf 2,4* [2,2], die Blähungsscores von 5,3 [2,7] auf 2,9* [2,3], und die wöchentliche Stuhlfrequenz von 2,7 [1,8] auf 4,4* [1,9] (alle: *p < 0,0001). Als häufigste Nebenwirkung wurde Diarrhoe in 5,1 % der Patienten dokumentiert.

Folgerung Linaclotid bessert unter „real life“-Bedingungen effektiv und mit guter Verträglichkeit sämtliche Kardinalsymptome des IBS-C. DRKS (www.drks.de/): DRKS00005088.

 
  • References

  • 1 Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA 2015; 313: 949-958
  • 2 Longstreth GF, Thompson WG, Chey WD. et al. Functional bowel disorders. Gastroenterology 2006; 130: 1480-1491
  • 3 Hungin APS, Chang L, Locke GR. et al. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther 2005; 21: 1365-1375
  • 4 Hungin APS, Whorwell PJ, Tack J. et al. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40 000 subjects. Aliment Pharmacol Ther 2003; 17: 643-650
  • 5 Drossman DA, Camilleri M, Mayer EA. et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002; 123: 2108-2131
  • 6 Dibonaventura M, Sun SX, Bolge SC. et al. Health-related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome. Curr Med Res Opin 2011; 27: 2213-2222
  • 7 Doshi JA, Cai Q, Buono JL. et al. Economic burden of irritable bowel syndrome with constipation: a retrospective analysis of health care costs in a commercially insured population. J Manag Care Pharm 2014; 20: 382-390
  • 8 Hulisz D. The burden of illness of irritable bowel syndrome: current challenges and hope for the future. J Manag Care Pharm 2004; 10: 299-309
  • 9 Guerin A, Carson RT, Lewis B. et al. The economic burden of treatment failure amongst patients with irritable bowel syndrome with constipation or chronic constipation: a retrospective analysis of a Medicaid population. J Med Econ 2014; 17: 577-586
  • 10 Bryant AP, Busby RW, Bartolini WP. et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci 2010; 86: 760-765
  • 11 Castro J, Martin C, Hughes PA. et al. A novel role of cyclic GMP in colonic sensory neurotransmission in healthy and TNBS-treated mice. Gastroenterology 2011; 140: S538
  • 12 European Medicines Agency. Summary of product characteristics: Constella. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002490/WC500135622.pdf . Accessed February 2, 2017
  • 13 Rey E, Mearin F, Alcedo J. et al. Optimizing the use of linaclotide in patients with constipation-predominant irritable bowel syndrome: an expert consensus report. Adv Ther 2017; 34: 587-598
  • 14 Chey WD, Lembo AJ, Lavins BJ. et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012; 107: 1702-1712
  • 15 Rao S, Lembo AJ, Shiff SJ. et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 2012; 107: 1714-1724
  • 16 Institute for Quality and Efficiency in Healthcare. Linaclotide in irritable bowel syndrome: added benefit not proven. Available at https://www.iqwig.de/en/press/press-releases/press-releases/linaclotide-in-irritable-bowel-syndrome-added-benefit-not-proven.3693.html . Accessed February 2, 2017
  • 17 Almirall stoppt vorerst Vertrieb von Linaclotid in Deutschland: Kein Konsens bei Preisverhandlungen mit GKV-SV. Available at https://www.journalmed.de/news/anzeigen/?id=42908 . Accessed February 2, 2017
  • 18 Spiegel B, Strickland A, Naliboff BD. et al. Predictors of patient-assessed illness severity in irritable bowel syndrome. Am J Gastroenterol 2008; 103: 2536-2543
  • 19 Spiegel B, Bolus R, Harris LA. et al. Measuring irritable bowel syndrome patient-reported outcomes with an abdominal pain numeric rating scale. Aliment Pharmacol Ther 2009; 30: 1159-1170