Interferon-Beta Injection in Multiple Sclerosis Patients Related to the Induction of Headache and Flu-Like Pain Symptoms: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory, and autoimmune disease characterised by the demyelination of the central nervous system. One of the main approaches for treating MS is the use of disease-modifying therapies (DMTs). Among the DMTs are interferons (IFNs), which are cytokines responsible for controlling the activity of the immune system while exerting immunomodulatory, antiviral, and antiproliferative activities. IFN-beta (IFN-β) is the first-choice drug used to treat relapsing-remitting MS. However, the administration of IFN-β causes numerous painful adverse effects, resulting in lower adherence to the treatment. Therefore, this study aimed to investigate the headache and flu-like pain symptoms observed after IFNβ injection in MS patients using a systematic review and meta-analysis of randomised controlled trials. A total of 2370 articles were identified through research databases. Nine articles were included (three involving IFNβ-1b and six involving IFNβ-1a). All studies included in the meta-analysis had a low risk of bias. The odds ratio of headache and flu-like pain symptoms increased in MS patients treated with IFN-β. Thus, the adverse effects of headache and flu-like pain symptoms appear to be linked to IFN-β treatment in MS. The protocol of the study was registered in the Prospective International Registry of Systematic Reviews (registration number CRD42021227593).