MSFIRST - utilising a longitudinal, prospective, comparative drug safety module for use in everyday MS clinical practice to evaluate and track incidence and characteristics of safety outcomes in MS patients on therapy over the long term

Introduction: MSFIRST, a sub-study of the MSBase registry, is an Australian multi-centre study to implement a user-friendly safety module to track incidence and characteristics of safety outcomes in MS patients. The comparative long term safety profile of disease-modifying drugs (DMD) in MS treatment is unknown and incidence and trends over time in serious adverse events (SAEs) are less well reported in real world practice.

Objective: MSFIRST is a prospective, longitudinal study, enrolling since 1 January 2012. The primary objective of this study is to track and compare the incidence of safety outcomes in MS patients who either receive DMD or no treatment.

Methods: Rates of SAE’s by treatment group including fingolimod (FTY), natalizumab (NAT) and combined group of interferon and glatiramer acetate (IFN/GA) were calculated as no. of eventsper 100 person-years of follow-up. The relative risk of SAE by treatment group was estimated using a longitudinal Poisson regression model offset by DMD exposure time and adjusted for age, sex and disease duration.

Results: At 6 April 2016 there were 3115 patients enrolled contributing 4590.8 person-years of follow-up at a mean (SD) of 17.4 months (14.2) per patient. 1303 adverse events have been observed. A total of 79 immunosuppression related or severe infection events, 75 herpes zoster, 56 non-melanoma skin cancer (NMSC) and 53 malignancy events observed at an incidence rate of 0.27, 0.33, 0.31 and 0.44 events per 100 person-years respectively. Natalizumab (NAT) was associated with 3.14 times the risk of infections (aRR 3.14; 95% CI 1.04, 9.46) relative to IFN/GA, whilst there was no difference between FTY and IFN/GA (aRR 2.06; 95% CI 0.72, 5.88). There was no difference in the risk of herpes zoster between FTY (aRR 1.00; 95% CI 0.44, 2.29) or NAT (aRR 1.37; 95% CI 0.54, 3.49) relative to IFN/GA group. Similarly, there was no difference in the risk of NMSC between IFN/GA and either FTY (aRR 0.79; 95% CI 0.28, 2.24) or NAT (aRR 0.79; 95% CI 0.21, 2.93). No difference in the risk of malignancy was observed between FTY (aRR 1.47; 95% CI 0.50, 4.30) or NAT (aRR 2.57; 95% CI 0.76, 8.70) compared with IFN/GA.

Conclusions: The establishment of a large, prospective multidrug safety module for use in routine practice has been successfulto date in Australia. Long term monitoring in clinical practice could provide important insights into both the incidence and timing of treatment-associated SAE’s.