Gender differences in safety issues during Fingolimod therapy: Evidence from a real‐life Relapsing Multiple Sclerosis cohort

Abstract

ObjectiveBenefits and risks of new therapies in Multiple Sclerosis (MS) must be balanced carefully and tailored to patients. We aimed to describe our experience with Fingolimod (FTY), correlating demographics, clinical and hematological features of the Relapsing MS (RMS) cohort with the occurring Adverse Events (AEs).Material and MethodsPretreatment screening tests, cardiological observation, and safety follow‐up data were analyzed in 225 RMS patients. Changes in continuous data were analyzed post hoc with Wilcoxon ranks test; categorical variables were examined using McNemar test. Two‐way repeated‐measures analysis of variance (ANOVA) was used to analyze differences between baseline characteristic of the cohorts and Liver Function Tests (LFT) alterations. Binary logistic regression models were used to identify which of the baseline factors influenced LFT alterations and the occurrence of infections.ResultsDuring 2 years of follow‐up 24 patients (10%) interrupted FTY. Discontinuation most often was due to AEs (n = 14) or breakthrough disease (n = 5). The most frequently AEs were infections (10.6%). After the first year patients showing an infectious episode were mostly female (p = .04). The infections did not correlate with the decrease in white blood cells or to lymphocyte count. AST and ALT alterations ​​were observed mostly in males (p = .002 and p = .01, respectively), and increase in GGT ​​was reported in subjects older at FTY beginning (p < .05).ConclusionsFor a patient‐centered safety monitoring of FTY, we may apply gender‐specific warnings, for the detection of transaminases abnormalities and infectious episodes.

Antioxidative effects of silymarin on the reduction of liver complications of fingolimod in patients with relapsing–remitting multiple sclerosis: A clinical trial study

“…Numerous studies confirm the results of the present study, and it has also been proven that by stopping the use of FTY720, the levels of hepatic transaminase are normalized. [ 24–27 ] In a study performed by Gordo et al, [ 28 ] silymarin had a significant effect on ALT enzyme in patients with chronic hepatitis C. Also, in Hajaghamohammadi et al's [ 29 ] study, they demonstrated a significant decrease in liver enzymes (ALT and AST) after silymarin use in nonalcoholic fatty liver disease. In our study, results demonstrated that the silymarin treatment for 6 months had an effective impact in decreasing the level of oxidative stress such as MDA and increase in antioxidant levels like TAC and TTG.…”

Adherence to laboratory monitoring among people taking oral drugs for multiple sclerosis: A Canadian population-based study

“…An observational study conducted in Italy found that ALT and AST abnormalities were detected mostly in men, rather than women, receiving fingolimod, and that a sex-specific approach may be useful for the monitoring of liver enzymes. 35 The factors that might explain such sex-related differences in adherence to laboratory monitoring, and the long-term consequences of them, remain to be explored.…”

The Effect of Fingolimod (FTY720) Treatment on Liver Enzyme Levels in Relapsing-Remitting Multiple Sclerosis Patients

“…It has been reported that ALT and AST levels can change significantly among different populations (15,16). Despite limited studies concerning confounder effects of demographic features on liver enzyme levels after FT, in general, increased ALT levels were observed 15% more frequently in male patients than in females (22,23).…”