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Interferon beta-1a (subcutaneous)

Classification: A

Drug products: Rebif, Rebif®

ATC code: L03AB07


Randomized controlled trials have shown a larger effect of s.c. interferon beta-1a in women regarding development of MS in patients with clinical isolated syndrome and in time to progression of MS in patients with progressive MS. A randomized trial found cognitive impairment to be more common in men with relapsing remitting MS. In an observational study, women reported more injection site reactions compared to men. However, all studies are relative small with fewer men than women included and low statistical power.

Additional information

Multiple Sclerosis (MS) is more common in women than in men [1, 2]. The gender gap in prevalence has been increasing and is today estimated to be two to three times more common in women than in men [1-3].

Several risk factors of MS have been suggested to have a larger impact on women. Sunlight deprivation, vitamin D deficiency, overweight, low urate levels, and smoking are such risk factors that increase the risk more in women than in men. Suggested mechanisms are that smoking yields increased levels of mature peripheral functioning T cells (OKT3+) in women [1]. Men have a worse prognosis and the role of sex hormones have been discussed [1, 2].

In a biomarker study of MS patients (30 men, 70 women) and healthy controls (24 men, 51 women), insulin growth factor binding protein1 (IGFBP1) was higher in women with MS compared to men [4]. The authors suggest this could reflect different MS progression pathways in men and women.

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis of the pharmacokinetics and dosing of s.c. interferon beta-1a have been found. However, no difference in dosing of interferon beta-1a in men and women have been suggested by the producer [9].


A randomized double-blind placebo controlled trial on the effect of interferon beta-1a s.c. in patients with secondary progressive MS (229 men, 389 women) with time to confirmed progression in disability as primary efficacy outcome found a significantly lower Hazard Ratio of 0.63 (95%CI 0.45-0.87) in women but not in men (Hazard Ratio 1.30 , 95%CI 0.85-2.01) [10].

A subgroup analysis of the REFLEX study on the effect on interferon beta-1a s.c. on development of clinically definite multiple sclerosis in patients with a first clinical demyelinating event suggestive of MS (185 men, 332 women) found a treatment effect of s.c. interferon beta-1a in women but not in men [11]. If this is indicative of a worse effect in men or a small sample size is difficult to say [11].

A prospective study in patients aged 18-50 years with relapsing remitting MS (86 men, 127 women) comparing the effect of two doses s.c. interferon beta-1a (22 µg and 44 µg) found a larger proportion of  cognitive impairment at year five in men but not in women [12].

Adverse effects

A retrospective registry study on self-reported injection site reactions after use of injectable MS modifying drugs ( 250 men, 946 women) found female sex, together with younger age to be associated with moderate injection site reactions for i.m. and s.c. interferon beta-1a and glatiramer acetate. Also, women using i.m. interferon beta-1a and glatiramer acetate reported more transient injection site reactions than men [7].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

In a US study based on questionnaires with a response rate of 44%, women with MS reported better awareness of disease symptoms and were found to express more positive perceptions of their ability to manage therapy with disease modifying drugs than men with MS [5].

In a survey study of patient risk tolerance in MS treatment 10 259 patients (response rate 53 %, resulting in 1196 men, 4250 women), women, elderly and those caring for dependents had a lower risk tolerance, while individuals with a more pronounced disability had a higher risk tolerance [6]. In a prospective multicenter study aiming to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome or early relapsing-remitting MS (355 men, 892 women) female sex was found to be associated with higher discontinuation rate for i.m. and s.c. interferon beta-1a [8].

Updated: 2020-08-28

Date of litterature search: 2017-12-07


  1. Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler. 2014;20:520-6. PubMed
  2. Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012;8:255-63. PubMed
  3. Johnson KM, Zhou H, Lin F, Ko JJ, Herrera V. Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year. J Manag Care Spec Pharm. 2017;23:844-852. PubMed
  4. Al-Temaimi R, AbuBaker J, Al-Khairi I, Alroughani R. Remyelination modulators in multiple sclerosis patients. Exp Mol Pathol. 2017;103(3):237-241. PubMed
  5. Vlahiotis A, Sedjo R, Cox ER, Burroughs TE, Rauchway A, Lich R. Gender differences in self-reported symptom awareness and perceived ability to manage therapy with disease-modifying medication among commercially insured multiple sclerosis patients. J Manag Care Pharm. 2010;16:206-16. PubMed
  6. Fox RJ, Salter A, Alster JM, Dawson NV, Kattan MW, Miller D et al. Risk tolerance to MS therapies: Survey results from the NARCOMS registry. Mult Scler Relat Disord. 2015;4(3):241-9. PubMed
  7. Stewart TM, Tran ZV. Injectable multiple sclerosis medications: a patient survey of factors associated with injection-site reactions. Int J MS Care. 2012;14:46-53. PubMed
  8. Meyniel C, Spelman T, Jokubaitis VG, Trojano M, Izquierdo G, Grand'Maison F et al. Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome. PLoS One. 2012;7:e38661. PubMed
  9. Rebif (interferon beta-1a). EPAR summary for the public. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000136/WC500048682.pdf. European Medicines Agency (EMA). 2011. [cited 2017-12-11]
  10. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: Clinical results. Neurology. 2001;56:1496-504. PubMed
  11. Freedman MS, De Stefano N, Barkhof F, Polman CH, Comi G, Uitdehaag BM et al. Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study. J Neurol. 2014;261:490-9. PubMed
  12. Patti F, Morra VB, Amato MP, Trojano M, Bastianello S, Tola MR et al. Subcutaneous interferon β-1a may protect against cognitive impairment in patients with relapsing-remitting multiple sclerosis: 5-year follow-up of the COGIMUS study. PLoS One. 2013;8:e74111. PubMed
  13. Concise. Stockholm: eHälsomyndigheten. 2016 [cited 2017-12-20.] länk

Authors: Mia von Euler

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson