Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study

Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting...

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Vydané v:	Lancet neurology Ročník 20; číslo 9; s. 709 - 720
Hlavní autori:	Brown, J William L, Cunniffe, Nick G, Prados, Ferran, Kanber, Baris, Jones, Joanne L, Needham, Edward, Georgieva, Zoya, Rog, David, Pearson, Owen R, Overell, James, MacManus, David, Samson, Rebecca S, Stutters, Jonathan, ffrench-Constant, Charles, Gandini Wheeler-Kingshott, Claudia A M, Moran, Carla, Flynn, Paul D, Michell, Andrew W, Franklin, Robin J M, Chandran, Siddharthan, Altmann, Daniel R, Chard, Declan T, Connick, Peter, Coles, Alasdair J
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England Elsevier Ltd 01.09.2021 Elsevier Limited
Predmet:	Acids Adult Adverse events Agonists Axons Bexarotene - administration & dosage Bexarotene - adverse effects Bexarotene - pharmacology Cholecystitis Clinical trials Demyelination Disability Double-Blind Method Double-blind studies Drug-Related Side Effects and Adverse Reactions Evoked Potentials, Visual - physiology Female Humans Hypothyroidism Licenses Magnetic Resonance Imaging Male Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - physiopathology Myelination Neutropenia Outcome Assessment, Health Care Patients Placebos Remyelination - drug effects Retinoid X receptors Retinoid X Receptors - agonists Safety Statistical analysis United Kingdom > UK
ISSN:	1474-4422, 1474-4465, 1474-4465
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Abstract	Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55). We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Multiple Sclerosis Society of the United Kingdom.
AbstractList	Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55). We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Multiple Sclerosis Society of the United Kingdom. Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18-50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene-placebo difference 0·16 pu, 95% CI -0·39 to 0·71; p=0·55). We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Multiple Sclerosis Society of the United Kingdom. Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.BACKGROUNDProgressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18-50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed.METHODSThis randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18-50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed.Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene-placebo difference 0·16 pu, 95% CI -0·39 to 0·71; p=0·55).FINDINGSBetween Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene-placebo difference 0·16 pu, 95% CI -0·39 to 0·71; p=0·55).We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies.INTERPRETATIONWe do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies.Multiple Sclerosis Society of the United Kingdom.FUNDINGMultiple Sclerosis Society of the United Kingdom. Summary Background Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. Methods This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Findings Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55). Interpretation We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Funding Multiple Sclerosis Society of the United Kingdom.
Author	Stutters, Jonathan Brown, J William L Kanber, Baris Franklin, Robin J M Altmann, Daniel R Georgieva, Zoya Needham, Edward Samson, Rebecca S Rog, David Chard, Declan T Flynn, Paul D Cunniffe, Nick G Gandini Wheeler-Kingshott, Claudia A M Jones, Joanne L Pearson, Owen R Overell, James ffrench-Constant, Charles MacManus, David Michell, Andrew W Chandran, Siddharthan Connick, Peter Prados, Ferran Moran, Carla Coles, Alasdair J
Author_xml	– sequence: 1 givenname: J William L orcidid: 0000-0002-7737-5834 surname: Brown fullname: Brown, J William L organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 2 givenname: Nick G orcidid: 0000-0002-7562-2838 surname: Cunniffe fullname: Cunniffe, Nick G email: ngc26@cam.ac.uk organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 3 givenname: Ferran orcidid: 0000-0002-7872-0142 surname: Prados fullname: Prados, Ferran organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 4 givenname: Baris orcidid: 0000-0003-2443-8800 surname: Kanber fullname: Kanber, Baris organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 5 givenname: Joanne L orcidid: 0000-0003-4974-1371 surname: Jones fullname: Jones, Joanne L organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 6 givenname: Edward orcidid: 0000-0001-7042-7462 surname: Needham fullname: Needham, Edward organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 7 givenname: Zoya orcidid: 0000-0002-9531-8884 surname: Georgieva fullname: Georgieva, Zoya organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 8 givenname: David orcidid: 0000-0002-7262-4248 surname: Rog fullname: Rog, David organization: Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK – sequence: 9 givenname: Owen R orcidid: 0000-0002-2712-0200 surname: Pearson fullname: Pearson, Owen R organization: Department of Neurology, Swansea Bay University Health Board, Swansea, UK – sequence: 10 givenname: James orcidid: 0000-0002-3998-9819 surname: Overell fullname: Overell, James organization: Product Development Neuroscience, F Hoffmann-La Roche, Basel, Switzerland – sequence: 11 givenname: David orcidid: 0000-0002-0902-977X surname: MacManus fullname: MacManus, David organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 12 givenname: Rebecca S orcidid: 0000-0002-0197-702X surname: Samson fullname: Samson, Rebecca S organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 13 givenname: Jonathan orcidid: 0000-0002-9151-0844 surname: Stutters fullname: Stutters, Jonathan organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 14 givenname: Charles orcidid: 0000-0002-5621-3377 surname: ffrench-Constant fullname: ffrench-Constant, Charles organization: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK – sequence: 15 givenname: Claudia A M orcidid: 0000-0002-4832-1300 surname: Gandini Wheeler-Kingshott fullname: Gandini Wheeler-Kingshott, Claudia A M organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 16 givenname: Carla orcidid: 0000-0002-7318-7166 surname: Moran fullname: Moran, Carla organization: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK – sequence: 17 givenname: Paul D surname: Flynn fullname: Flynn, Paul D organization: Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK – sequence: 18 givenname: Andrew W surname: Michell fullname: Michell, Andrew W organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 19 givenname: Robin J M orcidid: 0000-0001-6522-2104 surname: Franklin fullname: Franklin, Robin J M organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK – sequence: 20 givenname: Siddharthan orcidid: 0000-0001-6827-1593 surname: Chandran fullname: Chandran, Siddharthan organization: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK – sequence: 21 givenname: Daniel R surname: Altmann fullname: Altmann, Daniel R organization: Medical Statistics Department, London School of Hygiene & Tropical Medicine, London, UK – sequence: 22 givenname: Declan T orcidid: 0000-0003-3076-2682 surname: Chard fullname: Chard, Declan T organization: NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK – sequence: 23 givenname: Peter orcidid: 0000-0002-3892-8037 surname: Connick fullname: Connick, Peter organization: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK – sequence: 24 givenname: Alasdair J orcidid: 0000-0003-4738-0760 surname: Coles fullname: Coles, Alasdair J organization: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/34418398$$D View this record in MEDLINE/PubMed
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Snippet	Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor... Summary Background Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals,...
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SubjectTerms	Acids Adult Adverse events Agonists Axons Bexarotene - administration & dosage Bexarotene - adverse effects Bexarotene - pharmacology Cholecystitis Clinical trials Demyelination Disability Double-Blind Method Double-blind studies Drug-Related Side Effects and Adverse Reactions Evoked Potentials, Visual - physiology Female Humans Hypothyroidism Licenses Magnetic Resonance Imaging Male Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - physiopathology Myelination Neutropenia Outcome Assessment, Health Care Patients Placebos Remyelination - drug effects Retinoid X receptors Retinoid X Receptors - agonists Safety Statistical analysis
Title	Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study
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