Larazotide acetate in inflammatory bowel disease and mucosal barrier disorders: effect on the anchor outcome
In the population defined for inflammatory bowel disease and mucosal barrier disorders, what is the effect of Larazotide acetate compared with the comparator used in its contributing trials on the anchor outcome for this indication?
Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.
§1Abstract
§1.1Review question
In the population defined for inflammatory bowel disease and mucosal barrier disorders, what is the effect of Larazotide acetate compared with the comparator used in its contributing trials on the anchor outcome for this indication?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Chronic immune-mediated inflammation of the intestinal tract, or disorders of intestinal permeability including coeliac disease. |
| Intervention | Larazotide acetate administered as oral, before meals. |
| Comparator | The comparator used in each contributing trial, reported per trial rather than pooled across comparator types. |
| Outcomes | Anchor outcome for this indication: Clinical remission. Additional outcomes: Endoscopic healing; Faecal calprotectin; Intestinal permeability by lactulose–mannitol ratio. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 14 September 2024 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1,2]
§1.4Conclusion
Moderate certainty evidence from 2 contributing trials bears on the effect of Larazotide acetate on the anchor outcome for inflammatory bowel disease and mucosal barrier disorders. The estimate the Institute carries in the monograph is: A phase 2b trial met its primary endpoint on symptom scores at the 0.5 mg dose; the subsequent phase 3 trial was discontinued for futility at interim analysis. The Institute rates this moderate certainty for the conclusion that larazotide does not provide clinically meaningful benefit in coeliac disease at the doses studied. A positive phase 2b followed by a phase 3 futility stop is a textbook illustration of why phase 2 results should not be treated as conclusive, and the Institute cites this programme in its methodology documentation for that reason.
The conclusion rests on 2 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
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- Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. doi:10.1136/bmj.l4898 · PMID 31462531
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