Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment.
BACKGROUND
There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs.


OBJECTIVE
To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFNbeta) treatment response in a cohort of relapsing (RR) MS patients.


METHODS
A cohort of 2570 IFNbeta-treated RRMS was prospectively followed for up to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by 1 point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique.


RESULTS
The multivariate Cox Regression analyses showed that male patients had a significant (p=0.0097) lower risk for 1st relapse and a trend (p=0.0897) for a higher risk to reach 1 point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR=0.86; 95% CI=0.76-0.98; p=0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for 1 point EDSS progression (HR=1.33; 95% CI: 1.00-1.76; p<0.05) in the subgroup with a delayed treatment, but a still young age at the start of treatment.


CONCLUSIONS
The results of this exploratory analysis seem to suggest that male patients do not respond to IFNbeta treatment in the same way of females.
Trojano
M
M
Department of Neurological and Psychiatric Sciences University of Bari, Bari, Italy. mtrojano@neurol.uniba.it
Pellegrini
F
F
Paolicelli
D
D
Fuiani
A
A
Zimatore
G B
GB
Tortorella
C
C
Simone
I L
IL
Patti
F
F
Ghezzi
A
A
Portaccio
E
E
Rossi
P
P
Pozzilli
C
C
Salemi
G
G
Lugaresi
A
A
Bergamaschi
R
R
Millefiorini
E
E
Clerico
M
M
Lus
G
G
Vianello
M
M
Avolio
C
C
Cavalla
P
P
Iaffaldano
P
P
Direnzo
V
V
D'Onghia
M
M
Lepore
V
V
Livrea
P
P
Comi
G
G
Amato
M P
MP
D000328:Adult; D015331:Cohort Studies; D016001:Confidence Intervals; D004185:Disability Evaluation; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D007558:Italy; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D016017:Odds Ratio; D011358:Product Surveillance, Postmarketing; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
D007155:Immunologic Factors; D016899:Interferon-beta