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Interferon beta-1a (intramuscular)

Classification: A

Drug products: Avonex®, AVONEX®

ATC code: L03AB07

Summary

There are conflicting data regarding sex differences in effect of interferon beta-1a i.m. While some studies show a better effect in men with longer time to relapse other studies find no difference between men and women in effect. Depression as adverse effect that has been found to be more common in women than in men treated with i.m. interferon beta-1a. In an observational study, women reported more injection site reactions compared to men.

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

Effects

A registry study from Italy on prospectively followed interferon beta-treated patients with relapsing remitting MS (796 men, 1774 women) found that  men had a lower risk to first relapse than women [10]. A retrospective study analyzing the difference in effect, measured as annualized relapse rate (ARR), between men and women found ARR to be 0.29 and 0.44 in interferon beta-1a i.m. treated men and women, respectively [11]. In contrast, a study on pooled data from five RCTs on interferon beta-1a i.m. in relapsing remitting MS (the efficacy analysis included 251 men, 655 women) found no difference in effect [12].

Adverse effects

In the study on pooled data from five RCTs on interferon beta-1a i.m. in relapsing remitting MS (the safety analysis included 326 men, 850 women) women were found to report more headache regardless of treatment or placebo. Depression was more often reported in interferon beta-1a i.m. treated patients (19% in women and 14%, in men) than in the placebo groups (15%  in women and 9 % in men ) [12]. If persons with depression at baseline were excluded, 12% of women with interferon beta-1a treatment and 10 % with placebo reported depression compared to 9%  of men with interferon beta-1a i.m. treatment and 3 % with placebo [12]. Transient low hemoglobin was more frequently observed in interferon-beta 1a i.m. treated women compared to men while alanine transaminase (ALT) was higher in interferon-beta treated men than in women [12]. There was no difference in incidence of neutralizing antibodies [12].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 the Drugs and Birth Defects Database (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: 2019-02-26

Date of litterature search: 2017-12-07

References

  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. Avonex (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/000102/WC500029423.pdf. European Medicines Agency (EMA). 2011. [cited 2017-12-11]
  10. Trojano M, Pellegrini F, Paolicelli D, Fuiani A, Zimatore GB, Tortorella C et al. Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment. J Neurol Sci. 2009;286:109-13. PubMed
  11. Derfuss T, Ontaneda D, Nicholas J, Meng X, Hawker K. Relapse rates in patients with multiple sclerosis treated with fingolimod: Subgroup analyses of pooled data from three phase 3 trials. Mult Scler Relat Disord. 2016;8:124-30. PubMed
  12. Rudick RA, Kappos L, Kinkel R, Clanet M, Phillips JT, Herndon RM et al. Gender effects on intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis: analysis of 1406 patients. Mult Scler. 2011;17:353-60. 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