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Efficacy and Safety of Donidalorsen for Hereditary Angioedema.
Riedl, Marc A; Tachdjian, Raffi; Lumry, William R; Craig, Timothy; Karakaya, Gül; Gelincik, Asli; Stobiecki, Marcin; Jacobs, Joshua S; Gokmen, Nihal M; Reshef, Avner; Gompels, Mark M; Manning, Michael E; Bordone, Laura; Newman, Kenneth B; Treadwell, Sabrina; Wang, Sophie; Yarlas, Aaron; Cohn, Danny M.
Afiliação
  • Riedl MA; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Tachdjian R; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Lumry WR; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Craig T; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Karakaya G; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Gelincik A; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Stobiecki M; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Jacobs JS; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Gokmen NM; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Reshef A; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Gompels MM; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Manning ME; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Bordone L; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Newman KB; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Treadwell S; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Wang S; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Yarlas A; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
  • Cohn DM; From the Division of Allergy and Immunology, University of California at San Diego, La Jolla (M.A.R.), the Division of Allergy, Immunology, and Rheumatology, University of California at Los Angeles, Los Angeles (R.T.), Allergy and Asthma Clinical Research, Walnut Creek (J.S.J.), and Ionis Pharmaceut
N Engl J Med ; 391(1): 21-31, 2024 Jul 04.
Article em En | MEDLINE | ID: mdl-38819395
ABSTRACT

BACKGROUND:

Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression.

METHODS:

In this phase 3, double-blind, randomized trial, we assigned patients with hereditary angioedema to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25.

RESULTS:

A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P = 0.004); the median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group. Donidalorsen administered every 4 weeks resulted in an improvement in the least-squares mean total score for the change at week 25 on the Angioedema Quality-of-Life Questionnaire (scores range from 0 to 100, with a score of 100 indicating the worst possible quality of life) that was 18.6 points (95% CI, 9.5 to 27.7) better than that with placebo (P<0.001). The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity.

CONCLUSIONS:

Donidalorsen treatment reduced the hereditary angioedema attack rate, a finding that supports potential prophylactic use for hereditary angioedema. (Funded by Ionis Pharmaceuticals; OASIS-HAE ClinicalTrials.gov number, NCT05139810.).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligonucleotídeos Antissenso / Angioedemas Hereditários Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligonucleotídeos Antissenso / Angioedemas Hereditários Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: N Engl J Med Ano de publicação: 2024 Tipo de documento: Article