Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance
Identifieur interne : 000784 ( Pmc/Checkpoint ); précédent : 000783; suivant : 000785Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance
Auteurs : Ruth Keogh ; Chris Frost ; Gail Owen ; Rhian M. Daniel ; Doug R. Langbehn ; Blair Leavitt ; Alexandra Durr ; Raymund A. C. Roos ; G. Bernhard Landwehrmeyer ; Ralf Reilmann ; Beth Borowsky ; Julie Stout ; David Craufurd ; Sarah J. TabriziSource :
- PLoS Currents [ 2157-3999 ] ; 2016.
Abstract
Insufficient evidence exists to guide the long-term pharmacological management of Huntington’s disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such “inverse” associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
Url:
DOI: 10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb
PubMed: 26819833
PubMed Central: 4718719
Affiliations:
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<front><div type="abstract" xml:lang="en"><p> Insufficient evidence exists to guide the long-term pharmacological management of Huntington’s disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such “inverse” associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</p>
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<issn pub-type="epub">2157-3999</issn>
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<publisher-loc>San Francisco, USA</publisher-loc>
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<article-id pub-id-type="pmc">4718719</article-id>
<article-id pub-id-type="doi">10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
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<title-group><article-title>Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Keogh</surname>
<given-names>Ruth</given-names>
</name>
<aff>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Frost</surname>
<given-names>Chris</given-names>
</name>
<aff>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Owen</surname>
<given-names>Gail</given-names>
</name>
<aff>UCL Institute of Neurology, University College London, Queen Square, London, UK</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Daniel</surname>
<given-names>Rhian M.</given-names>
</name>
<aff>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Langbehn</surname>
<given-names>Doug R.</given-names>
</name>
<aff>Psychiatry, University of Iowa, Iowa City, Iowa, USA</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Leavitt</surname>
<given-names>Blair</given-names>
</name>
<aff>Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Durr</surname>
<given-names>Alexandra</given-names>
</name>
<aff>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Roos</surname>
<given-names>Raymund A.C.</given-names>
</name>
<aff>Neurology, Leiden University Medical Centre, Leiden, Netherlands</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Landwehrmeyer</surname>
<given-names>G. Bernhard</given-names>
</name>
<aff>Neurology, Ulm University, Ulm, Germany</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Reilmann</surname>
<given-names>Ralf</given-names>
</name>
<aff>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Borowsky</surname>
<given-names>Beth</given-names>
</name>
<aff>CHDI Management/CHDI Foundation, Princeton, NJ, USA</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Stout</surname>
<given-names>Julie</given-names>
</name>
<aff>School of Psychological Sciences, Monash University, VIC, Australia</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Craufurd</surname>
<given-names>David</given-names>
</name>
<aff>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Tabrizi</surname>
<given-names>Sarah J.</given-names>
</name>
<aff>Neurodegenerative Disease, UCL Institute of Neurology, London, UK</aff>
</contrib>
</contrib-group>
<pub-date pub-type="epub"><day>11</day>
<month>1</month>
<year>2016</year>
</pub-date>
<volume>8</volume>
<elocation-id>ecurrents.hd.8060298fac1801b01ccea6acc00f97cb</elocation-id>
<permissions><copyright-statement>© 2016 Keogh, Frost, Owen, Daniel, Langbehn, Leavitt, Durr, Roos, Landwehrmeyer, Reilmann, Borowsky, Stout, Craufurd, Tabrizi, et al</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Keogh, Frost, Owen, Daniel, Langbehn, Leavitt, Durr, Roos, Landwehrmeyer, Reilmann, Borowsky, Stout, Craufurd, Tabrizi, et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract><p> Insufficient evidence exists to guide the long-term pharmacological management of Huntington’s disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such “inverse” associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</p>
</abstract>
<funding-group><funding-statement>TRACK-HD is supported by the CHDI Foundation, Inc., a not for profit organization dedicated to finding treatments for Huntington’s disease. The authors have declared that no competing interests exist.</funding-statement>
</funding-group>
</article-meta>
</front>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name>
<name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name>
<name sortKey="Daniel, Rhian M" sort="Daniel, Rhian M" uniqKey="Daniel R" first="Rhian M." last="Daniel">Rhian M. Daniel</name>
<name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name>
<name sortKey="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name>
<name sortKey="Keogh, Ruth" sort="Keogh, Ruth" uniqKey="Keogh R" first="Ruth" last="Keogh">Ruth Keogh</name>
<name sortKey="Landwehrmeyer, G Bernhard" sort="Landwehrmeyer, G Bernhard" uniqKey="Landwehrmeyer G" first="G. Bernhard" last="Landwehrmeyer">G. Bernhard Landwehrmeyer</name>
<name sortKey="Langbehn, Doug R" sort="Langbehn, Doug R" uniqKey="Langbehn D" first="Doug R." last="Langbehn">Doug R. Langbehn</name>
<name sortKey="Leavitt, Blair" sort="Leavitt, Blair" uniqKey="Leavitt B" first="Blair" last="Leavitt">Blair Leavitt</name>
<name sortKey="Owen, Gail" sort="Owen, Gail" uniqKey="Owen G" first="Gail" last="Owen">Gail Owen</name>
<name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name>
<name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A. C." last="Roos">Raymund A. C. Roos</name>
<name sortKey="Stout, Julie" sort="Stout, Julie" uniqKey="Stout J" first="Julie" last="Stout">Julie Stout</name>
<name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J." last="Tabrizi">Sarah J. Tabrizi</name>
</noCountry>
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</affiliations>
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