A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis.
dc.contributor.author | Giovannoni, G | en_US |
dc.contributor.author | Knappertz, V | en_US |
dc.contributor.author | Steinerman, JR | en_US |
dc.contributor.author | Tansy, AP | en_US |
dc.contributor.author | Li, T | en_US |
dc.contributor.author | Krieger, S | en_US |
dc.contributor.author | Uccelli, A | en_US |
dc.contributor.author | Uitdehaag, BMJ | en_US |
dc.contributor.author | Montalban, X | en_US |
dc.contributor.author | Hartung, H-P | en_US |
dc.contributor.author | Pia Sormani, M | en_US |
dc.contributor.author | Cree, BAC | en_US |
dc.contributor.author | Lublin, F | en_US |
dc.contributor.author | Barkhof, F | en_US |
dc.date.accessioned | 2020-08-05T14:12:27Z | |
dc.date.available | 2020-02-20 | en_US |
dc.date.issued | 2020-08-25 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/66037 | |
dc.description.abstract | OBJECTIVE: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS). METHODS: In the randomized, double-blind, placebo-controlled, phase 2 study, ARPEGGIO (A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes), eligible patients with PPMS were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.5 mg or matching placebo. Percentage brain volume change (PBVC; primary endpoint) from baseline to week 48 was assessed by MRI. Secondary and exploratory endpoints included clinical and MRI measures. Efficacy endpoints were evaluated using a predefined, hierarchical statistical testing procedure. Safety was monitored throughout the study. The laquinimod 1.5 mg dose arm was discontinued on January 1, 2016, due to findings of cardiovascular events. RESULTS: A total of 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140). ARPEGGIO did not meet the primary endpoint of significant treatment effect with laquinimod 0.6 mg vs placebo on PBVC from baseline to week 48 (adjusted mean difference = 0.016%, p = 0.903). Laquinimod 0.6 mg reduced the number of new T2 brain lesions at week 48 (risk ratio 0.4; 95% confidence interval, 0.26-0.69; p = 0.001). Incidence of adverse events was higher among patients treated with laquinimod 0.6 mg (83%) vs laquinimod 1.5 mg (66%) and placebo (78%). CONCLUSIONS: Laquinimod 0.6 mg did not demonstrate a statistically significant effect on brain volume loss in PPMS at week 48. CLINICALTRIALSGOV IDENTIFIER: NCT02284568. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, although well tolerated, laquinimod 0.6 mg did not demonstrate a significant treatment effect on PBVC in patients with PPMS. | en_US |
dc.format.extent | e1027 - e1040 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Neurology | en_US |
dc.subject | Adult | en_US |
dc.subject | Atrophy | en_US |
dc.subject | Brain | en_US |
dc.subject | Disease Progression | en_US |
dc.subject | Double-Blind Method | en_US |
dc.subject | Female | en_US |
dc.subject | Humans | en_US |
dc.subject | Male | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Multiple Sclerosis, Chronic Progressive | en_US |
dc.subject | Quinolones | en_US |
dc.subject | Spinal Cord | en_US |
dc.subject | Treatment Outcome | en_US |
dc.title | A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1212/WNL.0000000000010284 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32651286 | en_US |
pubs.issue | 8 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 95 | en_US |
dcterms.dateAccepted | 2020-02-20 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |