Real‐world off‐label use of icatibant for acute management of non‐hereditary angioedema

Abstract

We retrospectively examined the indications and efficacy of off‐label use of the bradykinin B2 receptor antagonist icatibant. The clinical heterogeneity, variability of response to icatibant and lack of efficacy of adrenaline described in this audit highlights both the need for biomarkers that can rapidly distinguish between histaminergic and non‐histaminergic angioedema, and for guidelines to improve the utility of icatibant in the non‐hereditary angioedema setting.

Large Predominance of Off‐Label Prescriptions of C1‐Inhibitor Concentrates and Icatibant in a Real‐Life Setting: A Retrospective Clinical Study

“…We noted an underprescription of epinephrine in treating angioedema attacks of unknown origin with a prior epinephrine administration in only one third of first swelling episodes. Our results are far below those from a recent Australian study on off‐label use of icatibant 18 . In that study, epinephrine was provided before icatibant in 15 of the 18 prescriptions, while most cases were also for drug‐induced angioedema.…”

“…Our results are far below those from a recent Australian study on off-label use of icatibant. 18 In that study, epinephrine was provided before icatibant in 15 of the 18 prescriptions, while most cases were also for drug-induced angioedema. By contrast, Cai et al 17 reported a proportion of about 30% of prior administration of epinephrine in real-life prescriptions of icatibant, which is comparable to our findings.…”

“…Our retrospective clinical trial found that the therapeutic indications were explicitly mentioned for most inpatient prescriptions of C1INH concentrates and icatibant in our referral center. Although several observational and retrospective studies have evaluated the use of hereditary angioedema–specific drugs in various off‐label indications, few studies have assessed the prescribing of these medications in routine medical practice, with the only two existing reports examining icatibant prescriptions only 17,18 . In comparison to these studies, our aim was less to assess the effectiveness of these medications in potentially off‐label indications than to determine how and why they were prescribed.…”

“…Moreover, resistance to epinephrine has never been a diagnosis criterion of ACEi‐related angioedema in RCT, suggesting no requirement for prior epinephrine when this condition is suspected 11–13 . Yet one needs to recall that bradykinin‐mediated angioedema is less common than histaminergic angioedema, and it should not be assumed that angioedema occurring in a patient taking ACEis is always bradykinin mediated 18 . The prior administration of epinephrine, a readily available, rapidly effective, and inexpensive medication, seems reasonable in all cases of angioedema of uncertain origin before prescribing these costly drugs, especially since failure with epinephrine argues against a histaminergic pathomechanism 8…”

Angioedema and Fatty Acids

“…Although bradykinin-targeted therapy is useful for hereditary angioedema, it might also be useful for the treatment of drug-induced angioedema. Icatibant is effective for ACE inhibitor-triggered angioedema, which is also involved in the enhancement of bradykinin production, suggesting that treatment based on etiology is essential for the treatment of angioedema [27].…”