Vol.:(0123456789) 1 3 Journal of Neurology https://doi.org/10.1007/s00415-020-09771-x ORIGINAL COMMUNICATION Administration of subcutaneous interferon beta 1a in the evening: data from RELIEF study Francesco Patti 1  · Giovanni Bosco Zimatore 2  · Vincenzo Brescia Morra 3  · Umberto Aguglia 4  · Roberto Bruno Bossio 5  · Roberto Marziolo 6  · Paola Valentino 7  · Clara Grazia Chisari 1  · Antonio Capacchione 8  · Mario Zappia 1  on behalf of RELIEF Study Group Received: 3 February 2020 / Revised: 18 February 2020 / Accepted: 20 February 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Background Subcutaneous recombinant interferon-beta 1a (IFN-β1a SC) is indicated for treatment of relapsing multiple sclerosis (RMS); however, it is associated with development of fu-like syndrome (FLS) in 75% of patients. No recommenda- tions are available on whether evening or morning administration could induce better or worse FLS. Objective Primary objective was to investigate whether morning administration of IFN-β1a 44 µg (Rebif) would afect the severity of FLS versus evening administration, in patients with RMS. Secondary objectives were to investigate whether tim- ing of administration could lead to a better quality of life. Methods Multicenter, open-label, 12-week, randomized, controlled, parallel-group, phase 4 study. Results Of 217 patients screened at 29 Italian sites, 200 were included in the study. Among these, 104 patients were ran- domized to IFN-β1a SC administration in the morning and 96 in the evening. Morning administration resulted in higher FLS scores, as measured by the Multiple Sclerosis Treatment Concern Questionnaire, at week 4 (p = 0.0083) and week 8 (p = 0.0079); however, the diference was no longer signifcant at the end of 12 weeks. Conclusion IFN-β1a evening injections in the frst 8 weeks of treatment led to an improvement in FLS; when continuing therapy, time of administration could be decided according to patient’s lifestyle and preference. Keywords Multiple Sclerosis · Interferon beta · Flu-like syndrome · Time of administration · Self-injection · Quality of life Introduction Multiple Sclerosis (MS) is a chronic, infammatory, and degenerative, demyelinating disease of the central nervous system and is one of the most common causes of neurologic disability in young adults. It is characterized by multifocal recurrent events of neurologic symptoms and signs with variable recovery. There is currently no cure for MS; it is treated primarily with established disease-modifying drugs aimed at reducing relapses and slowing the progression to disability. Current frst-line injectable disease-modifying drugs include recom- binant beta interferons (IFN-β1a and IFN-β1b) and glati- ramer acetate, which represent the gold standard in modify- ing the course of MS [1, 2] Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00415-020-09771-x) contains supplementary material, which is available to authorized users. * Francesco Patti patti@unict.it 1 Department G. F. Ingrassia, Neuroscience Section, University of Catania, Via Santa Sofa, 78, 95123 Catania, Italy 2 U.O.C. Neurology, Ospedale Generale Regionale “F. Miulli”, Acquaviva delle Fonti, BA, Italy 3 Department of Neuroscience (NSRO), University of Naples Federico II, Napoli, Italy 4 Neurology Department, Hospital “Bianchi Melacrino Morelli”, Reggio Calabria, Italy 5 Multiple Sclerosis Center, Provincial Health Company of Cosenza, Cosenza, Italy 6 Neurology Department, Emergency Hospital “Cannizzaro”, Catania, Italy 7 Neurology Department, University Hospital “Località Germaneto”, Catanzaro, Italy 8 Medical Afairs Department, Merck Serono S.p.A., Rome, Italy