Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

Abstract

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.

Fig. 1

Analysis of the time to McDonald 2005 MS according to prespecified subgroups of a patient demographics and steroid treatment, and b MRI findings at the first clinical demyelinating event (ITT population; n = 517). Footnote a p value calculated by a multivariate Cox proportional hazards model. CI confidence interval, Gd+ gadolinium-enhancing, IFN interferon, ITT intent-to-treat, KM Kaplan–Meier, MRI magnetic resonance imaging, MS multiple sclerosis, qw once weekly, sc subcutaneous, tiw three times weekly

Fig. 2

Analysis of the time to CDMS according to prespecified subgroups of a patient demographics and steroid treatment, and b MRI findings at the first clinical demyelinating event (ITT population; n = 517). Footnote a p value calculated by a multivariate Cox proportional hazards model. CI confidence interval, CDMS clinically definite multiple sclerosis, Gd+ gadolinium-enhancing, IFN interferon, ITT intent-to-treat, KM Kaplan–Meier, MRI magnetic resonance imaging, qw once weekly, sc subcutaneous, tiw three times weekly

Fig. 3

Kaplan–Meier cumulative incidence curves for time to conversion to McDonald 2005 MS in patients negative (a) and positive (b) for McDonald 2010 MS at baseline. IFN interferon, MS multiple sclerosis, qw once weekly, sc subcutaneously, tiw three times weekly

Fig. 4

Conversion to McDonald 2005 MS, by McDonald 2010 MS status at baseline. Footnote a p value calculated by a Cox proportional hazards model, with treatment and MS status (McDonald or clinically definite MS: yes or no) as covariates. CI confidence interval, IFN interferon, MS multiple sclerosis, qw once weekly, sc subcutaneously, tiw three times weekly

Fig. 5

Kaplan–Meier cumulative incidence curves for time to conversion to CDMS in patients negative (a) and positive (b) for McDonald 2010 MS at baseline. CDMS clinically definite multiple sclerosis, IFN interferon, qw once weekly, sc subcutaneously, tiw three times weekly

Fig. 6

Conversion to CDMS, by McDonald 2010 MS status at baseline. Footnote a p value calculated by a Cox proportional hazards model, with treatment as a covariate. CDMS clinically definite multiple sclerosis, CI confidence interval, IFN interferon, qw once weekly, sc subcutaneously, tiw three times weekly