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<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="38705943">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://dx.doi.org/10.1007/s12325-024-02845-6"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3055&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38705943&amp;db=pubmed&amp;nlmid=8611864"
title="See full text options at Springer"
data-ga-category="full_text"
data-ga-action="Springer"
data-ga-label="38705943"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif" alt="Springer full text link"><span class="text">
Springer
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/38705943/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38705943&amp;db=pubmed&amp;nlmid=8611864"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="38705943"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/38705943/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/38705943/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="38705943" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F38705943%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="OukSwNc26geVjMTJOcz1rGC9nfq2n1TB5h4X9DFoGR1pddZzrvc3VO8NVj8egCrV"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
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><sup class="key">2</sup> Visible Analytics, Oxford, UK.</li>
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><sup class="key">3</sup> Institute of Health &amp; Wellbeing, University of Glasgow, Glasgow, UK.</li>
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><sup class="key">5</sup> F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.</li>
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Abstract
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<p>
<strong class="sub-title">
Introduction:
</strong>
Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease characterized by a loss of motor neurons and progressive muscle weakness. Children with untreated type 1 SMA never sit independently and require increasing levels of ventilatory support as the disease progresses. Without intervention, and lacking ventilatory support, death typically occurs before the age of 2 years. There are currently no head-to-head trials comparing available treatments in SMA. Indirect treatment comparisons are therefore needed to provide information on the relative efficacy and safety of SMA treatments for healthcare decision-making.
</p>
<p>
<strong class="sub-title">
Methods:
</strong>
The long-term efficacy and safety of risdiplam versus nusinersen in children with type 1 SMA was evaluated using indirect treatment comparison methodology to adjust for differences between population baseline characteristics, to reduce any potential bias in the comparative analysis. An unanchored matching-adjusted indirect comparison was conducted using risdiplam data from 58 children in FIREFISH (<a href="http://clinicaltrials.gov/show/NCT02913482" title="See in ClinicalTrials.gov">NCT02913482</a>) and published aggregate nusinersen data from 81 children obtained from the ENDEAR (<a href="http://clinicaltrials.gov/show/NCT02193074" title="See in ClinicalTrials.gov">NCT02193074</a>) and SHINE (<a href="http://clinicaltrials.gov/show/NCT02594124" title="See in ClinicalTrials.gov">NCT02594124</a>) clinical trials with at least 36 months of follow-up.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
Children with type 1 SMA treated with risdiplam had a 78% reduction in the rate of death, an 81% reduction in the rate of death or permanent ventilation, and a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen. Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module 2 motor milestone response and a 186% higher rate of achieving a ≥ 4-point improvement in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders compared with children treated with nusinersen.
</p>
<p>
<strong class="sub-title">
Conclusion:
</strong>
Long-term data supported risdiplam as a superior alternative to nusinersen in children with type 1 SMA. Video abstract available for this article. Video abstract (MP4 184542 KB).
</p>
</div>
<p>
<strong class="sub-title">
Keywords:
</strong>
Clinical trial; Indirect treatment comparison; MAIC; Matching-adjusted indirect comparison; Neuromuscular disease; Nusinersen; Propensity score matching; Risdiplam; SMA; Spinal muscular atrophy.
</p>
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<h2 class="title">
Plain language summary
</h2>
<p>
Risdiplam and nusinersen are two approved treatments for patients with type 1 spinal muscular atrophy (SMA). There are currently no head-to-head trials that compare the outcomes of these treatments in patients. This study conducted a statistical comparison of the efficacy and safety of risdiplam and nusinersen in children with type 1 SMA who received treatment for at least 36 months. Risdiplam data were collected from 58 children who participated in the FIREFISH trial (<a href="http://clinicaltrials.gov/show/NCT02913482" title="See in ClinicalTrials.gov">NCT02913482</a>). Published combined data were collected from 81 children treated with nusinersen who participated in the ENDEAR (<a href="http://clinicaltrials.gov/show/NCT02193074" title="See in ClinicalTrials.gov">NCT02193074</a>) and SHINE (<a href="http://clinicaltrials.gov/show/NCT02594124" title="See in ClinicalTrials.gov">NCT02594124</a>) trials. Outcomes from the two studies were compared using matching-adjusted indirect comparison (MAIC) methodology. MAIC adjusts for differences in baseline characteristics between patients in two trials to make the populations more similar and reduce bias in the comparison. Results suggested that children with type 1 SMA treated with risdiplam had a 78% reduction in the rate of death and an 81% reduction in the rate of death or permanent ventilation compared with children treated with nusinersen. With risdiplam, children also had a higher rate of achieving motor function responses, and a longer time to the first serious adverse event compared with children treated with nusinersen. These results support risdiplam as a superior alternative to nusinersen in children with type 1 SMA over 36 months of follow-up. Access to long-term data beyond 36 months would allow for additional indirect comparisons between SMA treatments. These comparisons are key to guiding treatment decision-making in the absence of head-to-head trials.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The SLR and data extraction were conducted by Bridge Medical Consulting Ltd., London, UK and funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland. ITC analyses were designed by Visible Analytics, UK, funded by F. Hoffmann-La Roche Ltd. Christos Kokaliaris and Julian Nam are employees of F. Hoffmann-La Roche Ltd. Julian Nam owns stocks in Roche. Rachel Evans is a former employee of Visible Analytics Ltd., which designed the analysis and received consultancy fees and expenses from F. Hoffmann-La Roche Ltd. Neil Hawkins and David Alexander Scott are partners/employees of Visible Analytics Ltd., which designed the analysis and received consultancy fees and expenses from F. Hoffmann-La Roche Ltd. Anadi Mahajan is an employee of Bridge Medical Consulting Ltd., which conducted this SLR and received consultancy fees and expenses from F. Hoffmann-La Roche Ltd. C Simone Sutherland was employed by F. Hoffmann-La Roche Ltd and owns stocks in Roche. Gautam Sajeev is an employee of Analysis Group, Inc. which received consulting fees from Genentech Inc. (a member of the Roche group) for this research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.</p>
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<div class="figures" id="figures">
<h2 class="title">
Figures
</h2>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f83/11133132/45116c4d5aea/12325_2024_2845_Fig1_HTML.gif"
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<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Overall survival in patients with… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> Overall survival in patients with type 1 SMA treated with risdiplam and nusinersen… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Fig. 1
</strong>
<div class="figure-caption-contents">Overall survival in patients with type 1 SMA treated with risdiplam and nusinersen (primary analysis). Unadjusted survival data from the pooled FIREFISH cohort (orange line) were plotted alongside the data from SHINE-ENDEAR (blue line). Patient baseline characteristics in FIREFISH were matched to the mean values of the baseline characteristics of the nusinersen arm in SHINE-ENDEAR using MAIC methodology, thus generating risdiplam-adjusted data (purple line). Characteristics that were used as adjustment factors in the primary analysis were age at first dose, disease duration, and baseline CHOP-INTEND score. PH test: <i>p</i>=0.893, not rejecting the null hypothesis. <i>CHOP-INTEND</i> Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, <i>MAIC</i> matching-adjusted indirect comparison, <i>PH</i> proportional hazard, <i>SMA</i> spinal muscular atrophy</div>
</figcaption>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f83/11133132/fa9e5ec91fc5/12325_2024_2845_Fig2_HTML.gif"
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<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Event-free survival in patients with… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> Event-free survival in patients with type 1 SMA treated with nusinersen and risdiplam… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 2
</strong>
<div class="figure-caption-contents">Event-free survival in patients with type 1 SMA treated with nusinersen and risdiplam (primary analysis). Event-free survival is defined as alive without the need for permanent ventilation. In FIREFISH, permanent ventilation was defined as ≥16 h of NIV/day or intubation for >21 consecutive days in the absence of, or following the resolution of, an acute reversible event or tracheostomy. In SHINE-ENDEAR, permanent ventilation was defined as either tracheostomy or ≥16 h of ventilation/day continuously for >21 days in the absence of an acute reversible event. Unadjusted survival data from the pooled FIREFISH cohort (orange line) were plotted alongside the data from SHINE-ENDEAR (blue line). Patient baseline characteristics in FIREFISH were matched to the mean values of the baseline characteristics of the nusinersen arm in SHINE-ENDEAR using MAIC methodology, thus generating risdiplam-adjusted data (purple line). Characteristics that were used as adjustment factors in the primary analysis were age at first dose, disease duration, and baseline CHOP-INTEND score. PH test: <i>p</i>=0.415, not rejecting the null hypothesis. <i>CHOP-INTEND</i> Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, <i>MAIC</i> matching-adjusted indirect comparison, <i>NIV</i> non-invasive ventilation, <i>PH</i> proportional hazard, <i>SMA</i> spinal muscular atrophy</div>
</figcaption>
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<figure class="figure-item "
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data-figure-id="Fig3">
<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f83/11133132/59b18eb53acd/12325_2024_2845_Fig3_HTML.gif"
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<div class="caption-wrap">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Time to HINE-2 motor milestone… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> Time to HINE-2 motor milestone response in patients with type 1 SMA treated… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 3
</strong>
<div class="figure-caption-contents">Time to HINE-2 motor milestone response in patients with type 1 SMA treated with risdiplam and nusinersen (primary analysis). Children were classed as a HINE-2 responder if more motor milestones showed improvement than worsening. Improvement was defined as a ≥2-point increase in the ability to kick (or maximal score) or a ≥1-point increase in head control, rolling, sitting, crawling, standing, or walking. Worsening was defined as a2-point decrease in the ability to kick (or lowest score) or a1-point decrease in head control, rolling, sitting, crawling, standing, or walking. Unadjusted survival data from the pooled FIREFISH cohort (orange line) were plotted alongside the data from SHINE-ENDEAR (blue line). Patient baseline characteristics in FIREFISH were matched to the mean values of the baseline characteristics of the nusinersen arm in SHINE-ENDEAR using MAIC methodology, thus generating risdiplam-adjusted data (purple line). Characteristics that were used as adjustment factors in the primary analysis were age at first dose, disease duration, and baseline CHOP-INTEND score. PH test: <i>p</i>=0.003, rejecting the null hypothesis. <i>CHOP-INTEND</i> Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, <i>HINE-2</i> Hammersmith Infant Neurological Examination, Module 2, <i>MAIC</i> matching-adjusted indirect comparison <i>PH</i> proportional hazard, <i>SMA</i> spinal muscular atrophy</div>
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<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Time to CHOP-INTEND response in… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 4 </p>
</strong>
<div class="figure-caption-contents"><p> Time to CHOP-INTEND response in patients with type 1 SMA treated with risdiplam… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 4
</strong>
<div class="figure-caption-contents">Time to CHOP-INTEND response in patients with type 1 SMA treated with risdiplam and nusinersen (primary analysis). A CHOP-INTEND response was defined as a ≥4-point improvement in CHOP-INTEND score from baseline. Unadjusted survival data from the pooled FIREFISH cohort (orange line) were plotted alongside the data from SHINE-ENDEAR (blue line). Patient baseline characteristics in FIREFISH were matched to the mean values of the baseline characteristics of the nusinersen arm in SHINE-ENDEAR using MAIC methodology, thus generating risdiplam-adjusted data (purple line). Characteristics that were used as adjustment factors in the primary analysis were age at first dose, disease duration, and baseline CHOP-INTEND score. PH test: <i>p</i>=0.020, rejecting the null hypothesis. <i>CHOP-INTEND</i> Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, <i>MAIC</i> matching-adjusted indirect comparison, <i>PH</i> proportional hazard; <i>SMA</i> spinal muscular atrophy</div>
</figcaption>
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<p> Fig. 5 </p>
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<div class="figure-caption-contents"><p> Time to first SAE in… </p></div>
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<p> Fig. 5 </p>
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<div class="figure-caption-contents"><p> Time to first SAE in patients with type 1 SMA treated with nusinersen… </p></div>
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Fig. 5
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<div class="figure-caption-contents">Time to first SAE in patients with type 1 SMA treated with nusinersen and risdiplam (primary analysis). Unadjusted survival data from the pooled FIREFISH cohort (orange line) were plotted alongside the data from SHINE-ENDEAR (blue line). Patient baseline characteristics in FIREFISH were matched to the mean values of the baseline characteristics of the nusinersen arm in SHINE-ENDEAR using MAIC methodology, thus generating risdiplam-adjusted data (purple line). Characteristics that were used as adjustment factors in the primary analysis were age at first dose, disease duration, and baseline CHOP-INTEND score. PH test: <i>p</i>=0.263, not rejecting the null hypothesis. <i>CHOP-INTEND</i> Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, <i>MAIC</i> matching-adjusted indirect comparison, <i>PH</i> proportional hazard, <i>SAE</i> serious adverse event, <i>SMA</i> spinal muscular atrophy</div>
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