# Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study.

- **DOI:** [10.1007/s12325-025-03226-3](https://doi.org/10.1007/s12325-025-03226-3)
- **Rating:** Sound (3.0 out of 5)
- **Verdict:** EMPOWER adds useful long-term real-world confirmation of lanadelumab’s effectiveness, but its uncontrolled, asymmetrically measured before-after comparison limits causal certainty.
- **Framework version:** v5.9
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-09-18
- **Evaluation page:** https://www.nabu.science/paper/10.1007%2Fs12325-025-03226-3

## Key claims

1. In patients newly treated with lanadelumab, the mean observed attack rate decreased by 85% after lanadelumab initiation
   - Support: Tentative
   - Type: Primary finding
   - Basis: uncontrolled before-after comparison with retrospective baseline ascertainment and prospective post-treatment diaries
   - Location: Abstract, Results; Results, HAE Attack Rate
2. Patients established on lanadelumab had an observed attack rate of 0.20 during 36 months' follow-up
   - Support: Well-supported
   - Type: Secondary
   - Basis: direct descriptive estimate from the 91-patient established-treatment cohort
   - Location: Abstract, Results; Results, Patients Established on Lanadelumab
3. No new safety signals were identified.
   - Support: Tentative
   - Type: Secondary
   - Basis: descriptive safety surveillance without special monitoring for injection-site reactions
   - Location: Abstract, Conclusion; Discussion, Safety

## Strengths

- **Longer multicenter real-world follow-up** The 109-patient full analysis set was drawn from 30 sites and followed for up to 36 months, extending the scale and duration of earlier real-world reports.
  - Dimension: contribution
  - Location: Methods, Study Design and Population; Results, Patient Disposition; Discussion, paragraph 4
- **Transparent longitudinal attack-rate reporting** The paper reports pre-treatment, early-state, steady-state, and cumulative attack rates, alongside incidence-rate ratios and an age- and sex-adjusted sensitivity model.
  - Dimension: methodological rigour
  - Location: Methods, Statistical Analysis; Results, Figs. 3–4
- **Quantitative connection to prior evidence** The Discussion directly compares EMPOWER attack rates with HELP, HELP OLE, and smaller Canadian and French observational studies rather than merely listing prior work.
  - Dimension: positioning
  - Location: Discussion, paragraphs 2–3

## Limitations

- **Asymmetric before-after outcome measurement** Pre-enrollment attacks were reconstructed through physician eCRFs and recall or medical history, whereas study-period attacks were captured prospectively in patient diaries. This difference directly affects confidence in the reported 85% reduction.
  - Dimension: methodological rigour
  - Location: Methods, Study Assessments; Statistical Analysis; Fig. 1 footnote
- **Causal wording exceeds observational identification** The Discussion states that lanadelumab “effectively reduced” attacks despite the absence of a concurrent comparator and limited control of time-varying confounding or regression to the mean.
  - Dimension: reporting
  - Location: Discussion, opening paragraph; Conclusion
- **Early stopping truncates long-term evidence** The sponsor ended the study early based on consistency with phase 3 data, leaving incomplete follow-up for some participants and narrowing the basis for the long-term-persistence narrative.
  - Dimension: methodological rigour
  - Location: Results, Patient Disposition; Discussion, Limitations

## Reliability checks

Caveats (4 of 4 checks).

- **Internal coherence:** Noted. The main effectiveness comparison has asymmetric outcome ascertainment across periods, and sponsor-initiated early termination truncated follow-up for some participants. These disclosed features affect confidence in the magnitude and long-term persistence of the findings without contradicting the reported numerical results.
- **Research conduct:** Clean. The article declares ethics review, written informed consent, trial registration, and industry sponsorship. No supplied-text concern meets the threshold for a conduct notation.
- **Reference integrity:** Clean. 24 of 24 checkable references verified
  - 28 references in manuscript
  - 4 are books, websites or datasets — counted, but not index-checkable
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Clean
- **Summary:** No retraction or expression of concern found in Crossref (includes Retraction Watch).
- **Last checked:** 2026-10-17