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

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.

Schlüsselwörter

Funktionelle GI Erkrankungen - Reizdarmsyndrom - Bauchschmerzen - Obstipation - Linaclotid

Key words

functional GI diseases - irritable bowel syndrome - abdominal pain - constipation - linaclotide

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