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WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.
,” investigators said.
The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.
“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
TRAP-MS Trial
The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.
Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.
Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).
An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.
Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
Worsening Symptoms
The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.
These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”
“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.
None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”
Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
‘Undesirable’ or ‘Premature’?
Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.
“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”
In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”
Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.
Dr. Green, who was not involved in the new study, said he is skeptical of the findings.
“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”
Dr. Bielekova disagreed, and said she stands by the findings.
The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.
“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.
Regardless, Dr. Green urged caution when considering whether to use the drug.
“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”
NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
A version of this article appeared on Medscape.com.
WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.
,” investigators said.
The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.
“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
TRAP-MS Trial
The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.
Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.
Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).
An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.
Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
Worsening Symptoms
The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.
These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”
“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.
None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”
Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
‘Undesirable’ or ‘Premature’?
Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.
“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”
In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”
Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.
Dr. Green, who was not involved in the new study, said he is skeptical of the findings.
“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”
Dr. Bielekova disagreed, and said she stands by the findings.
The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.
“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.
Regardless, Dr. Green urged caution when considering whether to use the drug.
“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”
NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
A version of this article appeared on Medscape.com.
WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.
,” investigators said.
The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.
“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
TRAP-MS Trial
The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.
Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.
Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).
An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.
Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
Worsening Symptoms
The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.
These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”
“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.
None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”
Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
‘Undesirable’ or ‘Premature’?
Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.
“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”
In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”
Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.
Dr. Green, who was not involved in the new study, said he is skeptical of the findings.
“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”
Dr. Bielekova disagreed, and said she stands by the findings.
The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.
“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.
Regardless, Dr. Green urged caution when considering whether to use the drug.
“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”
NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
A version of this article appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>167305</fileName> <TBEID>0C04F06F.SIG</TBEID> <TBUniqueIdentifier>MD_0C04F06F</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>ACTRIMS Clemastine</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240318T110240</QCDate> <firstPublished>20240318T114813</firstPublished> <LastPublished>20240318T114813</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240318T114813</CMSDate> <articleSource>FROM ACTRIMS FORUM 2024</articleSource> <facebookInfo/> <meetingNumber>5304-24</meetingNumber> <byline>Randy Dotinga</byline> <bylineText>RANDY DOTINGA</bylineText> <bylineFull>RANDY DOTINGA</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Researchers halted an arm of a clinical trial of clemastine fumarate for MS after a fivefold increase in disease progression was reported in three participants,</metaDescription> <articlePDF/> <teaserImage/> <teaser>Three patients demonstrated increased disability five times faster than their 18-month baseline, which triggered stoppage of the trial. </teaser> <title>In Unexpected Finding, Clemastine Fumarate Linked to Worsening Symptoms in MS</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2024</pubPubdateYear> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName>January 2021</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>msrc</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">22</term> <term>59347</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">251</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>In Unexpected Finding, Clemastine Fumarate Linked to Worsening Symptoms in MS</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">WEST PALM BEACH, FLORIDA</span> — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.</p> <p><span class="tag metaDescription">Researchers halted an arm of a clinical trial of <span class="Hyperlink">clemastine</span> fumarate for MS after a fivefold increase in disease progression was reported in three participants, triggering “stoppage criteria</span>,” investigators said.<br/><br/>The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.<br/><br/>“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”<br/><br/>The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).<br/><br/></p> <h2>TRAP-MS Trial</h2> <p>The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a <span class="Hyperlink"><a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32346-2/abstract">small clinical trial</a></span> reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.</p> <p>Clemastine fumarate is one of four drugs in the ongoing <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT03109288">TRAP-MS</a></span> phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.<br/><br/>Other drugs in the study include the diabetes drug <span class="Hyperlink">pioglitazone</span> (Actos), the muscle relaxant <span class="Hyperlink">dantrolene</span> (Ryanodex, Revonto, and Dantrium), and the <span class="Hyperlink">idiopathic pulmonary fibrosis</span> drug <span class="Hyperlink">pirfenidone</span> (Pirespa).<br/><br/>An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.<br/><br/>Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.<br/><br/></p> <h2>Worsening Symptoms</h2> <p>The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.</p> <p>These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”<br/><br/>“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.<br/><br/>None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”<br/><br/>Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.<br/><br/></p> <h2>‘Undesirable’ or ‘Premature’?</h2> <p>Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.</p> <p>“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”<br/><br/>In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”<br/><br/>Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.<br/><br/>Dr. Green, who was not involved in the new study, said he is skeptical of the findings.<br/><br/>“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”<br/><br/>Dr. Bielekova disagreed, and said she stands by the findings.<br/><br/>The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.<br/><br/>“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.<br/><br/>Regardless, Dr. Green urged caution when considering whether to use the drug.<br/><br/>“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”<br/><br/>NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/unexpected-finding-clemastine-fumarate-linked-worsening-2024a10004ss">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ACTRIMS FORUM 2024