A Comparison Study of Efficacy and Safety of a Biosimilar Form of Intramuscular Βeta-interferon I-a Versus the Reference Product: A Randomized Controlled Clinical Trial in Iran

Document Type : Short Comunication


1 Department of Brain and Cognitive Sciences, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran.

2 Department of Neurology, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.

3 Actoverco Pharmaceuticals, Tehran, Iran.

4 Clinical Trial Center, Tehran University of Medical Sciences, Tehran, Iran.

5 Shefa Neuroscience Research Center, Tehran, Iran.

6 Department of Radiology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran.

7 Department of Neurology, Faculty of Medical, Tehran University of Medical Sciences, Tehran, Iran.


We compared the efficacy and safety of a biosimilar form of beta-interferon-1a (Actovex) versus the reference product in the treatment of relapsing remitting multiple sclerosis (RRMS). In a double blind, randomized phase 3 clinical trial, we evaluated 138 patients with RRMS that were allocated to receive the biosimilar medication and the reference treatment (30 μg intramuscular, weekly for one year). We investigated changes in EDSS, relapse rate and MRI changes within one year.
In sixty-nine patients who were allocated to each arm and analyzed mean age and its standard deviation was 32.4 ± 8.8 and 31.5 ± 8 for the biosimilar medication and the reference arm respectively. One-year follow-up revealed a mean difference of 0.084 in EDSS (95% CI: 0.069-0.237) between the two groups in favor of the biosimilar medication. This value did not exceed the predefined non-inferiority margin of 0.1. There were no statistically significant differences in relapse rate and systemic and local adverse events of the two groups. The results show that the biosimilar interferon 1-a is non-inferior to the reference product in terms of efficacy while it demonstrates comparable safety. In conclusion the biosimilar interferon 1-a can be considered as an effective and safe alternative to the reference product due to lower cost and more availability.


Main Subjects

Compston A, Lassmann H and McDonald I .The Story
of Multiple Sclerosis. McAlpine’s Multiple Sclerosis. 4th
ed. Churchill Livingstone, London (2006) 3-68.
Deleu D, Mir D, Al Tabouki A, Mesraoua R, Mesraoua
B, Akhtar N, Al Hail H, D′souza A, Melikyan G, Imam
YZ, Osman Y, Elalamy O, Sokrab T, Kamran S, Ruiz
Miyares F and Ibrahim F. Prevalence, demographics
and clinical characteristics of multiple sclerosis in
Qatar. Mult. Scler. J. (2013) 19: 816–9.
Pakdaman H, Amini Harandi A, Gharagozli K, Abbasi
M, Tabassi A, Ashrafi F, Ghaffarpor M, Sharifi S,
Delavar Kasmae H, Assarzadegan F, Arabahmadi
M and Behnam B. Health-related quality of life in
patients with relapsing-remitting multiple sclerosis
treated with subcutaneous interferon β-1a in Iran. Int.
J. Neurosci. (2017) 127: 501–7.
Yamout B, Barada W, Tohme RA, Mehio-Sibai A,
Khalifeh R and El-Hajj T. Clinical characteristics of
multiple sclerosis in Lebanon. J. Neurol. Sci. (2008)
270: 88–93.
Alroughani R, Ahmed SF and Al-Hashel J.
Demographics and clinical characteristics of multiple
sclerosis in Kuwait. Eur. Neurol. (2014) 72: 181–5.
Akhtar N, Elsetouhy A, Deleu D, Kamran S, Alhail
H, Elalamy O, Mesraoua B, Sokrab T, Kamil H,
Melikyan G, D′souza A, Osman Y and Imam Y. Newly
diagnosed multiple sclerosis in state of Qatar. Clin.
Neurol. Neurosurg. (2013) 115: 1333–7.
Multiple sclerosis in adults: management. National
 Nabavi SM et al. / IJPR (2019), 18 (3): 1632-1638
Institute for Health and Care Excellence. 2014 Oct
[cited 2018 Sep 26]; Available from: URL: https://
Kleinschnitz C, Niemczyk G, Rehberg-Weber K and
Wernsdörfer C. Interferon Beta-1a (AVONEX®) as a
Treatment Option for Untreated Patients with Multiple
Sclerosis (AXIOM): A Prospective, Observational
Study. Int. J. Mol. Sci. (2015) 16: 15271-86.
Etemadifar M, Janghorbani M and Shaygannejad
V. Comparison of Betaferon, Avonex, and Rebif in
treatment of relapsing–remitting multiple sclerosis.
Acta. Neurol. Scand. (2006) 113: 283-7.
Nafissi S, Azimi A, Amini-Harandi A, Salami S and
Heshmat R. Comparing efficacy and side effects of a
weekly intramuscular biogeneric/biosimilar interferon
beta-1a with Avonex in relapsing remitting multiple
sclerosis: A double blind randomized clinical trial.
Clin. Neurol. Neurosurg. (2012) 114: 986-9.
Graziella Filippini, L. Interferons in relapsing remitting
multiple sclerosis: a systematic review. Lancet (2003)
361: 545-52.
De Stefano N, Sormani MP, Stubinski B, Blevins G,
Drulovic JS, Issard D, Shotekov P and Gasperini C.
Efficacy and safety of subcutaneous interferon beta1a in relapsing–remitting multiple sclerosis: Further
outcomes from the Improve study. J. Neurol. Sci.
(2012) 312: 97-101.
AVONEX® (interferon beta-1a) Intramuscular
Injection, Full Prescribing Information. Availble
from: URL: http://www.avonex.com/pdfs/Avonex_