@article{discovery10107080,
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
           month = {August},
           pages = {e1027--e1040},
         journal = {Neurology},
            year = {2020},
          volume = {95},
          number = {8},
           title = {A randomized, placebo-controlled phase 2 trial of laquinimod in primary progressive multiple sclerosis},
        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 PPMS patients 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: 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 versus 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\%) versus 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.},
             url = {https://doi.org/10.1212/WNL.0000000000010284},
          author = {Giovannoni, G and Knappertz, V and Steinerman, JR and Tansy, AP and Li, T and Krieger, S and Uccelli, A and Uitdehaag, BMJ and Montalban, X and Hartung, H-P and Sormani, MP and Cree, BAC and Lublin, F and Barkhof, F}
}