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2016 ; 16
(ä): 176
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Laquinimod efficacy in relapsing-remitting multiple sclerosis: how to understand
why and if studies disagree
#MMPMID27639853
Cutter GR
; Knappertz V
; Sasson N
; Ladkani D
BMC Neurol
2016[Sep]; 16
(ä): 176
PMID27639853
show ga
BACKGROUND: The results of two randomized phase 3 trials that investigated the
use of laquinimod in patients with relapsing-remitting multiple sclerosis were
analyzed using a propensity score model. METHODS: The propensity score in each
study was defined as the probability of an individual patient being assigned to
either the laquinimod or placebo study arm. The analysis included two main
stages: (1) calculation of a propensity score for each patient, given a broad set
of baseline covariates that included second-degree interactions, and (2)
incorporation of the propensity score as another covariate into the predefined
primary analysis model to test the treatment effect of laquinimod (0.6 mg/d) vs
placebo on the annualized relapse rate (ARR). RESULTS: The BRAVO study showed
baseline imbalances for T2 volume and the proportion of patients with gadolinium
(Gd)-enhancing lesions, both parameters known to correlate with risk of relapse.
Adjustment using the propensity score as a categorical variable showed that the
estimated difference in ARR between laquinimod and placebo was 0.078, in favor of
laquinimod. In ALLEGRO, the baseline Gd-enhancing lesion mean score was higher
for placebo vs laquinimod. When the primary analysis model was adjusted for the
propensity score as a categorical variable, the covariate adjusted difference in
mean ARR between laquinimod and placebo was 0.084, in favor of laquinimod.
CONCLUSIONS: Propensity scores addressing differences in baseline characteristics
may be helpful to better understand whether observed treatment effect differences
in randomized controlled trials are accurate results or result from inherent
differences between patients with multiple sclerosis.