Laquinimod, an oral quinolone-3-carboxamide, was shown to slow the progression of disability and reduce rates of relapse in patients with relapsing-remitting multiple sclerosis (RRMS), according to results of a recent phase 3 study [N Engl J Med. 2012;366(11):1000-1009].
ALLEGRO (Assessment of Oral Laquinimod in Preventing Progression in Multiple Sclerosis) was a 24-month, double-blind, randomized, placebo-controlled, multicenter trial of 1106 patients with RRMS that evaluated the safety, efficacy, and tolerability of oral laquinimod. In addition to a relapsing-remitting course of at least 6 months, patients had to be between 18 and 55 years of age, with a score of no more than 5.5 on the Kurtzke Expanded Disability Status Scale (EDSS) for study eligibility.
The primary end point was the number of confirmed relapses (the appearance of ≥1 new, or reappearance of neurologic abnormalities lasting for at least 48 hours after an improved neurologic state for at least 30 days). Secondary end points were disability progression according to EDSS and Multiple Sclerosis Functional Composite (MSFC) scores.
Patients were randomized to either oral laquinimod at a dose of 0.6 mg once daily or a matching placebo capsule, and were assessed at screening, baseline, and at months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24. EDSS scores were evaluated every 3 months and MSFC scores every 6 months. Patients also underwent magnetic resonance imaging (MRI) annually. The researchers used Poisson regression in their analysis to determine relapse rates.
A total of 437 patients in the laquinimod group and 427 patients in the placebo group completed the entire study. Results showed the mean (±) annualized relapse rate for the 24-month treatment period was significantly reduced for patients given laquinimod compared with those given placebo (0.30±0.02 vs 0.39±0.03, P=.002). Results also showed that 62.9% of patients in the laquinimod group were relapse-free compared with 52.2% of patients given placebo (P<.001).
The time to first relapse was longer for patients receiving laquinimod compared with those given placebo, and the risk of relapse was significantly reduced for patients given laquinimod (hazard ratio, 0.72; 95% CI, 0.59-0.87; P<.001). The researchers also found the annualized rate of relapse requiring hospitalization or intravenous treatment with glucocorticoids was significantly lower for patients in the laquinimod group versus those who received placebo (0.24 vs 0.33, P<.001).
The risk of disability progression, as assessed by EDSS scores, was also significantly reduced for the laquinimod group compared with the placebo group (11.1% vs 15.7%; hazard ratio, 0.64; P=.01). Confirmed disability progression at the last study assessment was also lower for patients given laquinimod (9.8% vs 14% of the placebo group; P=.04). Mean EDSS scores at the last assessment were 2.68 and 2.79 for the laquinimod and placebo groups, respectively (P=.05). MSFC scores between the groups did not differ significantly throughout the study. MRI findings showed patients given laquinimod had a reduction in gadolinium-enhancing lesions, as well as reductions in new or enlarged lesions on T2-weighted images, and less brain-volume loss compared with the patients given placebo (P<.001 for all).
There were a total of 122 serious adverse events (11.1% and 9.5% of the laquinimod and placebo groups, respectively). Among a total of 3309 adverse events, 87% and 81% of patients given laquinimod and placebo, respectively, reported at least 1 event. The 3 most common events associated with laquinimod included abdominal pain (5.8% vs 2.9% for placebo), back pain (16.4% vs 9% for placebo), and cough (7.5% vs 4.5% for placebo).