Table 10Summary of Findings of the Primary Studies

Main Study FindingsAuthors’ Conclusion
De Stefano et al., 201419,a

Clinical effectiveness @ 24 months (REFLEX trial) IFN β-1a 44 mcg SC thrice weekly (n = 171) vs. IFN β-1a 30 mcg SC weekly (n = 175) vs. placebo (n = 171)

Study completion rates: 146 (85.4%) vs. 156 (89.1%) vs. 146 (85.4%), respectively; P = NR

Mean number of lesion per patient per scanb

Mean (±SD) number of CUA lesions: 0.6±1.15 vs. 1.23±4.26 vs. 2.70±5.23, respectively; indicating that both regimen were more effective than placebo

Relative reduction in the number of CUA lesions compared to placebo: 2.10 vs. 1.47; P = 0.002; indicating that the thrice weekly regimen is more effective than the weekly regimen

Analysis using an adjusted negative binomial model (P = NR)

CUA lesions: 0.50 vs. 0.95 vs. 2.58, respectively

New T2 non-enhancing lesions: 0.17 vs. 0.24 vs. 0.55, respectively

New T1 Gd+ lesions: 0.06 vs. 0.17 vs. 0.72, respectively

New T1 non-enhancing lesions: 0.18 vs. 0.26 vs. 0.41, respectively

All results favour active therapy (statistical significance of the effect size was not reported)

IFN β-1a 44 mcg SC thrice weekly vs. placebob

RR of CUA lesions: 0.19 (CI, 0.14 to 0.26); P <0.001

RR of new T2 non-enhancing lesions: 0.30 (0.23 to 0.40); P <0.001

RR of new T1 Gd+ lesions: 0.08 (CI, 0.05 to 0.13); P <0.001

RR of new T1 non-enhancing lesions: 0.43 (CI, 0.33 to 0.57); P <0.001

All results favour active therapy

IFN β-1a 30 mcg SC weekly vs. placebob

RR of CUA lesions: 0.37 (CI, 0.27 to 0.50); P <0.001

RR of new T2 non-enhancing lesions: 0.43 (CI, 0.32 to 0.57); P <0.001

RR of new T1 Gd+ lesions: 0.24 (CI, 0.16 to 0.35); P <0.001

RR of new T1 non-enhancing lesions: 0.63 (CI, 0.48 to 0.81); P 0.004

All results favour active therapy

IFN β-1a 44 mcg SC thrice weekly vs. IFN β-1a 30 mcg SC weeklyb

RR of CUA lesions: 0.52 (CI, 0.38 to 0.71); P = 0.002

RR of new T2 non-enhancing lesions: 0.71 (CI, 0.53 to 0.95); P = 0.012

RR of new T1 Gd+ lesions: 0.35 (CI, 0.23 to 0.54); P <0.001

RR of new T1 non-enhancing lesions: 0.69 (CI, 0.53 to 0.91); P = 0.008

All results favour higher dose (statistical significance of the effect size was not reported)

Subgroup analysis

HR for age <30 years vs ≥30 years: 1.69 (CI, 1.31 to 2.18); favouring the older group

HR for ≥1 vs 0 Gd+ lesions: 2.67 (CI, 2.05 to 3.47); favouring those with no lesions

HR for ≥9 vs <9 T2 non-enhancing lesions: 4.93 (CI, 3.66 to 6.63); favouring those with fewer than 9 lesions

There was no significant effect of monofocal versus multifocal presentation, use of steroids during the first event or patient sex.

Median (IQR) change in volume from baselineb (P = NR)

T2 non-enhancing lesions: −128.7 mm3(−721.0 to 42.5) vs. −37.9 mm3(−609.3 to 177.4) vs. +51.5 mm3 (−194.6 to 617.3), respectively; favouring active therapies over placebo T1 Gd+ lesions: 0 mm3 (−88.7 to 0.0) vs. 0 mm3 (−71.55 to 0.00) vs. 0 mm3 (−54.40 to 11.40), respectively; slightly favouring active therapies over placebo

T1 non-enhancing lesions: No change vs. no change vs. +31.5 mm3, respectively; favouring active therapies over placebo

Safety

No new or unexpected safety signals were found

“This secondary analysis of REFLEX found improved MRI outcomes in patients treated with both dosing regimens compared with placebo, and also found additional benefit of the higher-dose regimen. Together, these data support the rationale for early subcutaneous IFN β-1a treatment of patients with CIS suggestive of MS; however, these potential benefits of early treatment have to be balanced against the risk of treatment.” (p 652)

CI = 95% confidence interval; CIS = clinically isolated syndrome; CUA = combined unique active; Gd+ = gadolinium-enhancing; IFN = interferon; HR = hazard ratio; IQR = interquartile range; MRI = magnetic resonance imaging; MS = multiple sclerosis; NR = not reported; REFLEX = Rebif flexible dosing in early MS; RR = relative risk; SC = subcutaneously; SD = standard deviation

a

Reported on a subset of patients included in the systematic review18

b

It is unclear how many patients were enrolled at the time that measurements were recorded. The authors indicate in their text that 146, 156, and 146 patients, respectively completed the study in the 44 mcg SC IFN β-1a thrice weekly, 30 mcg SC IFN β-1a weekly, and placebo groups. Meanwhile, figure 1 suggests that at 24 months, the number of patients were 113, 119, and 88, respectively.

From: Glatiramer Acetate and Interferon Beta 1a and 1b for Clinically Isolated Syndrome: A Review of Clinical Effectiveness and Guidelines

Cover of Glatiramer Acetate and Interferon Beta 1a and 1b for Clinically Isolated Syndrome: A Review of Clinical Effectiveness and Guidelines
Glatiramer Acetate and Interferon Beta 1a and 1b for Clinically Isolated Syndrome: A Review of Clinical Effectiveness and Guidelines [Internet].
Williams D, Butcher R.
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