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N Engl J Med. 2012 Mar 15;366(11):1000-9. doi: 10.1056/NEJMoa1104318.

Placebo-controlled trial of oral laquinimod for multiple sclerosis.

Collaborators (167)

Comi G, Boiko A, Filippi M, Jeffery D, Kappos L, Montalban X, McFarland H, Bauer K, Galay N, Larrey D, Metz L, White W, Filippi M, Absinta M, Longoni G, Pagani E, Rocca M, Weber J, Franta C, Lampi C, Shotekov P, Bozhinov S, Deleva N, Haralanov L, Hristova SI, Petrov I, Milanov I, Kremenchutzky M, Rabinovitch H, Ayotte C, GrandMaison F, Lamontagne A, Leckey R, Lee L, Hradilek P, Kanovsky P, Gross-Paju K, Taba P, Vermersch P, Rumbach L, Clavelou P, Confavreux C, Pelletier J, Edan G, Shakarishvili R, Tsiskaridze A, Becker E, Chan A, Eggers J, Haas J, Heesen C, Heidenreich F, Koehler J, Koelmel HW, Linker R, Oschmann P, Rauer S, Maschke M, Mueller M, Reifschneider G, Wildemann B, Steinbrecher A, Tumani H, Ziebold U, Ziemssen T, Kanya J, Jakab G, Valikovics A, Bartos L, Karussis D, Rawashdeh H, Karni A, Chapman J, Comi G, Caputo D, Centonze D, Cottone S, Ghezzi A, Maimone D, Montanari E, Plewnia K, Scarpini E, Metra M, Rastenyte D, Sceponaviciute S, De Jong B, Frequin S, Visser L, Zwanikken C, Selmaj K, Blaszczyk B, Wajgt A, Nowak R, Jasinska E, Brola W, Sobkowiak-Osinska M, Kapustecki J, Zaborski J, Panea CA, Simu M, Bulboaca AC, Balasa RI, Carciumaru N, Boyko A, Skoromets A, Stolyarov I, Perfilyev S, Odinak M, Amelina O, Malkova N, Gustov A, Volkova L, Shutov A, Drulovic J, Vojinovic S, Montalban X, Arroyo R, Saiz Hinarejos A, Brieva L, Ramio L, Meca Lallana J, Amigo Jorrin Md, Prieto JM, Munoz Gracia D, Aladro Y, Coret F, Escartin A, Diez Tejedor E, Hillert J, Olddon T, Martin C, Idiman E, Sharrack B, Giovannoni G, Young C, Nehrych T, Moskovko S, Kobys T, Ipatov A, Loganovskyi K, Abou Zeid N, Jeffery D, Dihenia B, Carpenter A, Flitman S, Gazda S, Goodman A, Green B, Gupta A, Herbert J, Hughes B, Jacobs A, Khatri B, Lynch S, Miller T, Markowitz C, Murray R, Pardo G, Parry G, Gottschalk G, Rossman H, Scaberry S, Thomas F, Turel A, Anderson G, Twyman C, Wynn D.

Author information

Department of Neurology and Institute of Experimental Neurology, Università Vita-Salute San Raffaele, Milan, Italy.



Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis.


We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging.


Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (±SE) annualized relapse rate (0.30±0.02 vs. 0.39±0.03, P=0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07, respectively; P<0.001 for both comparisons). Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod (5%) and 8 receiving placebo (2%).


In this phase 3 study, oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by Teva Pharmaceutical Industries; number, NCT00509145.).

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