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Hereditary Angioedema Attacks in Patients Receiving Long-Term Prophylaxis: A Systematic Review.

Hilary J Longhurst1, Mauro Cancian2, Vesna Grivcheva-Panovska3

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Summary

Long-term prophylaxis (LTP) reduces hereditary angioedema (HAE) attacks but does not eliminate them. Patients on LTP still experience attacks, including laryngeal ones, requiring on-demand therapy.

Keywords:
Attack-free rateHereditary angioedemaLong-term prophylaxisOn-demand therapySystematic review

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Area of Science:

  • Immunology
  • Genetics
  • Pharmacology

Background:

  • Long-term prophylaxis (LTP) is used to reduce hereditary angioedema (HAE) attack frequency.
  • Characterizing breakthrough attacks in patients on LTP is crucial for optimizing management.

Approach:

  • A systematic review of PubMed-identified studies evaluated LTP use in HAE-C1INH patients.
  • Included studies reported on plasma-derived C1 inhibitor (pdC1INH), lanadelumab, berotralstat, androgens, or antifibrinolytics.
  • Forty-five primary studies met the inclusion criteria for analysis.

Key Points:

  • Attack-free rates varied among LTP agents; lanadelumab showed higher rates during steady-state treatment.
  • Prophylactic effects were more significant for peripheral attacks than abdominal or laryngeal ones.
  • Laryngeal attacks occurred in 2-7% of cases, and on-demand therapy was used in 49-94% of breakthrough attacks.

Conclusions:

  • HAE-C1INH patients on LTP can experience attacks in all locations, including the larynx.
  • On-demand therapy remains essential for managing breakthrough HAE attacks, even with prophylaxis.
  • Outcomes of on-demand therapy use during LTP were not reported, highlighting a need for further research.