Therapy - immunomodulation - Part IIFriday, September 30, 2005, 15:30 - 17:00
48-week open safety study with a high-dose oral laquinimod in MS patientsM. Sandberg-Wollheim, T. Nederman, A. Linde (Lund, S)
Background: Laquinimod is a novel oral immunomodulatory substance developed for disease modifying treatment in multiple sclerosis (MS). In a 24-week, randomized, placebo controlled phase II study, laquinimod at 0.3 mg/day was shown to significantly reduce the number of active lesions in relapsing MS patients (Polman et al. Neurology 2005;64:987-991). Safety evaluation showed that laquinimod was well tolerated.
Goal: The aim of this study was to investigate the safety of laquinimod at a dose higher than the dose previously shown to be effective in reducing the number of active lesions.
Methods: Patients with confirmed MS (EDSS 0-6.5) were enrolled in this 48-week study of laquinimod at 0.9 mg/day given orally. The protocol allowed temporary dose interruptions as well as dose reduction to 0.6 mg/day.
Results: Twenty-two patients, aged 23 to 61 years, representing a broad spectrum of MS patients with EDSS scores 0-6.5 (mean EDSS=4.27) were included in the study. All patients except one (Eurasian) were Caucasian; 77% were female.
Seventeen patients (77%) completed the 48-week treatment period on the original dose of 0.9 mg/day. Two patients were treated at the reduced dose level of 0.6 mg/day and three patients discontinued treatment during the course of the study. The majority of observed adverse events (AEs) were mild to moderate and transient. The most common AEs were headache, nasopharyngitis, arthralgia, back pain, abdominal pain, influenza, myalgia and abnormal laboratory values. There were two serious AEs (hospitalization due to urinary tract infection and influenza) both regarded as unrelated to study drug.
Four patients improved during the treatment period; in one the EDSS score decreased from 5.5 to 3.5; in three patients the EDSS score was reduced with 0.5 points. In one patient the EDSS score increased from 6.5 to 7. The remaining patients were stable. Seventeen patients (77%) remained relapse free during the study.
Conclusions: Treatment with laquinimod at 0.9 mg/day given orally was well tolerated in most patients, although the incidence of potentially treatment related AEs, in some cases resulting in drug holiday or dose reduction was higher than experienced at 0.3 mg/day in the previous phase II study. Patients remained clinically stable or improved in disability. The majority of patients remained relapse free during the treatment period.