Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial
IMPORTANCE: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. OBJECTIVE: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. DESIGN, SETTING, AN...
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| creator | Banerji, Aleena Riedl, Marc A Bernstein, Jonathan A Cicardi, Marco Longhurst, Hilary J Zuraw, Bruce L Busse, Paula J Anderson, John Magerl, Markus Martinez-Saguer, Inmaculada Davis-Lorton, Mark Zanichelli, Andrea Li, H. Henry Craig, Timothy Jacobs, Joshua Johnston, Douglas T Shapiro, Ralph Yang, William H Lumry, William R Manning, Michael E Schwartz, Lawrence B Shennak, Mustafa Soteres, Daniel Zaragoza-Urdaz, Rafael H Gierer, Selina Smith, Andrew M Tachdjian, Raffi Wedner, H. James Hebert, Jacques Rehman, Syed M Staubach, Petra Schranz, Jennifer Baptista, Jovanna Nothaft, Wolfram Maurer, Marcus |
| description | IMPORTANCE: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. OBJECTIVE: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. INTERVENTIONS: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. MAIN OUTCOME AND MEASURES: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. RESULTS: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were −1.49 (95% CI, −1.90 to −1.08; P |
| doi_str_mv | 10.1001/jama.2018.16773 |
| format | Article |
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Henry ; Craig, Timothy ; Jacobs, Joshua ; Johnston, Douglas T ; Shapiro, Ralph ; Yang, William H ; Lumry, William R ; Manning, Michael E ; Schwartz, Lawrence B ; Shennak, Mustafa ; Soteres, Daniel ; Zaragoza-Urdaz, Rafael H ; Gierer, Selina ; Smith, Andrew M ; Tachdjian, Raffi ; Wedner, H. James ; Hebert, Jacques ; Rehman, Syed M ; Staubach, Petra ; Schranz, Jennifer ; Baptista, Jovanna ; Nothaft, Wolfram ; Maurer, Marcus</creator><creatorcontrib>Banerji, Aleena ; Riedl, Marc A ; Bernstein, Jonathan A ; Cicardi, Marco ; Longhurst, Hilary J ; Zuraw, Bruce L ; Busse, Paula J ; Anderson, John ; Magerl, Markus ; Martinez-Saguer, Inmaculada ; Davis-Lorton, Mark ; Zanichelli, Andrea ; Li, H. Henry ; Craig, Timothy ; Jacobs, Joshua ; Johnston, Douglas T ; Shapiro, Ralph ; Yang, William H ; Lumry, William R ; Manning, Michael E ; Schwartz, Lawrence B ; Shennak, Mustafa ; Soteres, Daniel ; Zaragoza-Urdaz, Rafael H ; Gierer, Selina ; Smith, Andrew M ; Tachdjian, Raffi ; Wedner, H. James ; Hebert, Jacques ; Rehman, Syed M ; Staubach, Petra ; Schranz, Jennifer ; Baptista, Jovanna ; Nothaft, Wolfram ; Maurer, Marcus ; HELP Investigators ; for the HELP Investigators</creatorcontrib><description>IMPORTANCE: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. OBJECTIVE: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. INTERVENTIONS: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. MAIN OUTCOME AND MEASURES: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. RESULTS: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were −1.49 (95% CI, −1.90 to −1.08; P < .001); −1.44 (95% CI, −1.84 to −1.04; P < .001); and −1.71 (95% CI, −2.09 to −1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). CONCLUSIONS AND RELEVANCE: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. TRIAL REGISTRATION: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805</description><identifier>ISSN: 0098-7484</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.2018.16773</identifier><identifier>PMID: 30480729</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adolescent ; Adult ; Aged ; Angioedema ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Child ; Clinical trials ; Disease prevention ; Double-Blind Method ; Edema ; Effectiveness ; Female ; Females ; Hereditary Angioedema Types I and II - classification ; Hereditary Angioedema Types I and II - prevention & control ; Humans ; Impact analysis ; Injections, Subcutaneous - adverse effects ; Kallikrein ; Male ; Middle Aged ; Monoclonal antibodies ; Original Investigation ; Patients ; Placebo effect ; Plasma kallikrein ; Plasma Kallikrein - antagonists & inhibitors ; Prophylaxis ; Quality of Life ; Young Adult</subject><ispartof>JAMA : the journal of the American Medical Association, 2018-11, Vol.320 (20), p.2108-2121</ispartof><rights>Copyright American Medical Association Nov 27, 2018</rights><rights>Copyright 2018 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a353t-d2cc5577c6e509519b3a99b9cd538b510e3419162b169c0d958e002fc30734fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.2018.16773$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2018.16773$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,777,781,882,3327,27905,27906,76238,76241</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30480729$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Banerji, Aleena</creatorcontrib><creatorcontrib>Riedl, Marc A</creatorcontrib><creatorcontrib>Bernstein, Jonathan A</creatorcontrib><creatorcontrib>Cicardi, Marco</creatorcontrib><creatorcontrib>Longhurst, Hilary J</creatorcontrib><creatorcontrib>Zuraw, Bruce L</creatorcontrib><creatorcontrib>Busse, Paula J</creatorcontrib><creatorcontrib>Anderson, John</creatorcontrib><creatorcontrib>Magerl, Markus</creatorcontrib><creatorcontrib>Martinez-Saguer, Inmaculada</creatorcontrib><creatorcontrib>Davis-Lorton, Mark</creatorcontrib><creatorcontrib>Zanichelli, Andrea</creatorcontrib><creatorcontrib>Li, H. Henry</creatorcontrib><creatorcontrib>Craig, Timothy</creatorcontrib><creatorcontrib>Jacobs, Joshua</creatorcontrib><creatorcontrib>Johnston, Douglas T</creatorcontrib><creatorcontrib>Shapiro, Ralph</creatorcontrib><creatorcontrib>Yang, William H</creatorcontrib><creatorcontrib>Lumry, William R</creatorcontrib><creatorcontrib>Manning, Michael E</creatorcontrib><creatorcontrib>Schwartz, Lawrence B</creatorcontrib><creatorcontrib>Shennak, Mustafa</creatorcontrib><creatorcontrib>Soteres, Daniel</creatorcontrib><creatorcontrib>Zaragoza-Urdaz, Rafael H</creatorcontrib><creatorcontrib>Gierer, Selina</creatorcontrib><creatorcontrib>Smith, Andrew M</creatorcontrib><creatorcontrib>Tachdjian, Raffi</creatorcontrib><creatorcontrib>Wedner, H. James</creatorcontrib><creatorcontrib>Hebert, Jacques</creatorcontrib><creatorcontrib>Rehman, Syed M</creatorcontrib><creatorcontrib>Staubach, Petra</creatorcontrib><creatorcontrib>Schranz, Jennifer</creatorcontrib><creatorcontrib>Baptista, Jovanna</creatorcontrib><creatorcontrib>Nothaft, Wolfram</creatorcontrib><creatorcontrib>Maurer, Marcus</creatorcontrib><creatorcontrib>HELP Investigators</creatorcontrib><creatorcontrib>for the HELP Investigators</creatorcontrib><title>Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>IMPORTANCE: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. OBJECTIVE: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. INTERVENTIONS: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. MAIN OUTCOME AND MEASURES: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. RESULTS: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were −1.49 (95% CI, −1.90 to −1.08; P < .001); −1.44 (95% CI, −1.84 to −1.04; P < .001); and −1.71 (95% CI, −2.09 to −1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). CONCLUSIONS AND RELEVANCE: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. 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Henry</creatorcontrib><creatorcontrib>Craig, Timothy</creatorcontrib><creatorcontrib>Jacobs, Joshua</creatorcontrib><creatorcontrib>Johnston, Douglas T</creatorcontrib><creatorcontrib>Shapiro, Ralph</creatorcontrib><creatorcontrib>Yang, William H</creatorcontrib><creatorcontrib>Lumry, William R</creatorcontrib><creatorcontrib>Manning, Michael E</creatorcontrib><creatorcontrib>Schwartz, Lawrence B</creatorcontrib><creatorcontrib>Shennak, Mustafa</creatorcontrib><creatorcontrib>Soteres, Daniel</creatorcontrib><creatorcontrib>Zaragoza-Urdaz, Rafael H</creatorcontrib><creatorcontrib>Gierer, Selina</creatorcontrib><creatorcontrib>Smith, Andrew M</creatorcontrib><creatorcontrib>Tachdjian, Raffi</creatorcontrib><creatorcontrib>Wedner, H. James</creatorcontrib><creatorcontrib>Hebert, Jacques</creatorcontrib><creatorcontrib>Rehman, Syed M</creatorcontrib><creatorcontrib>Staubach, Petra</creatorcontrib><creatorcontrib>Schranz, Jennifer</creatorcontrib><creatorcontrib>Baptista, Jovanna</creatorcontrib><creatorcontrib>Nothaft, Wolfram</creatorcontrib><creatorcontrib>Maurer, Marcus</creatorcontrib><creatorcontrib>HELP Investigators</creatorcontrib><creatorcontrib>for the HELP Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Banerji, Aleena</au><au>Riedl, Marc A</au><au>Bernstein, Jonathan A</au><au>Cicardi, Marco</au><au>Longhurst, Hilary J</au><au>Zuraw, Bruce L</au><au>Busse, Paula J</au><au>Anderson, John</au><au>Magerl, Markus</au><au>Martinez-Saguer, Inmaculada</au><au>Davis-Lorton, Mark</au><au>Zanichelli, Andrea</au><au>Li, H. Henry</au><au>Craig, Timothy</au><au>Jacobs, Joshua</au><au>Johnston, Douglas T</au><au>Shapiro, Ralph</au><au>Yang, William H</au><au>Lumry, William R</au><au>Manning, Michael E</au><au>Schwartz, Lawrence B</au><au>Shennak, Mustafa</au><au>Soteres, Daniel</au><au>Zaragoza-Urdaz, Rafael H</au><au>Gierer, Selina</au><au>Smith, Andrew M</au><au>Tachdjian, Raffi</au><au>Wedner, H. James</au><au>Hebert, Jacques</au><au>Rehman, Syed M</au><au>Staubach, Petra</au><au>Schranz, Jennifer</au><au>Baptista, Jovanna</au><au>Nothaft, Wolfram</au><au>Maurer, Marcus</au><aucorp>HELP Investigators</aucorp><aucorp>for the HELP Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>2018-11-27</date><risdate>2018</risdate><volume>320</volume><issue>20</issue><spage>2108</spage><epage>2121</epage><pages>2108-2121</pages><issn>0098-7484</issn><eissn>1538-3598</eissn><abstract>IMPORTANCE: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. OBJECTIVE: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. INTERVENTIONS: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. MAIN OUTCOME AND MEASURES: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. RESULTS: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were −1.49 (95% CI, −1.90 to −1.08; P < .001); −1.44 (95% CI, −1.84 to −1.04; P < .001); and −1.71 (95% CI, −2.09 to −1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). CONCLUSIONS AND RELEVANCE: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. TRIAL REGISTRATION: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>30480729</pmid><doi>10.1001/jama.2018.16773</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0098-7484 |
| ispartof | JAMA : the journal of the American Medical Association, 2018-11, Vol.320 (20), p.2108-2121 |
| issn | 0098-7484 1538-3598 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6583584 |
| source | MEDLINE; American Medical Association Journals |
| subjects | Adolescent Adult Aged Angioedema Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Child Clinical trials Disease prevention Double-Blind Method Edema Effectiveness Female Females Hereditary Angioedema Types I and II - classification Hereditary Angioedema Types I and II - prevention & control Humans Impact analysis Injections, Subcutaneous - adverse effects Kallikrein Male Middle Aged Monoclonal antibodies Original Investigation Patients Placebo effect Plasma kallikrein Plasma Kallikrein - antagonists & inhibitors Prophylaxis Quality of Life Young Adult |
| title | Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T15%3A22%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20Lanadelumab%20Compared%20With%20Placebo%20on%20Prevention%20of%20Hereditary%20Angioedema%20Attacks:%20A%20Randomized%20Clinical%20Trial&rft.jtitle=JAMA%20:%20the%20journal%20of%20the%20American%20Medical%20Association&rft.au=Banerji,%20Aleena&rft.aucorp=HELP%20Investigators&rft.date=2018-11-27&rft.volume=320&rft.issue=20&rft.spage=2108&rft.epage=2121&rft.pages=2108-2121&rft.issn=0098-7484&rft.eissn=1538-3598&rft_id=info:doi/10.1001/jama.2018.16773&rft_dat=%3Cproquest_pubme%3E2154217313%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2154217313&rft_id=info:pmid/30480729&rft_ama_id=2716564&rfr_iscdi=true |