Interferon ß-1b Treatment by Cyclical Administration

Summary

The therapy with Interferon-ß-1b reduces the inflammatory component of multiple sclerosis with positive effects on the disease course. The 8 MUI dose at alternate days is kept constant for years. About 1/3 of patients suspend treatment by three years due to side effects or suspected or accepted ineffectiveness. The main objective of the study is to verify the safety and effectiveness of a cyclical administration (a month of suspension after two of treatment) from the beginning of treatment. There is the possibility that a scheme envisaging therapy free intervals can reduce the onset of negative feedbacks (antagonising the drug therapeutic effect) compared to the standard administration protocol. This might also result in an increase of the drug effectiveness and/or in a longer duration of effectiveness itself. Finally, cyclical administration allows patients to spend actual periods of "therapeutic vacation", with positive psychological effects.

Timeline

Start

2005-11

Primary completion

2010-08

Completion

2011-01

Outcome

Met primary endpoint

paper allowing to significantly reject the null hypothesis of a ratio ≥1.2 and to meet the primary end-point of non-inferiority PMID 31379701 ↗

Publications

• Background Steinman L. Immunotherapy of multiple sclerosis: the end of the beginning. Curr Opin Immunol. 2001 Oct;13(5):597-600. doi: 10.1016/s0952-7915(00)00266-1.
• Background Calabresi PA, Stone LA, Bash CN, Frank JA, McFarland HF. Interferon beta results in immediate reduction of contrast-enhanced MRI lesions in multiple sclerosis patients followed by weekly MRI. Neurology. 1997 May;48(5):1446-8. doi: 10.1212/wnl.48.5.1446.
• Background Richert ND, Zierak MC, Bash CN, Lewis BK, McFarland HF, Frank JA. MRI and clinical activity in MS patients after terminating treatment with interferon beta-1b. Mult Scler. 2000 Apr;6(2):86-90. doi: 10.1177/135245850000600206.
• Background Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol. 2000 Oct;1(4):311-6. doi: 10.1038/79758.
• Background Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, de Waal Malefyt R, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation. Science. 1999 Feb 19;283(5405):1183-6. doi: 10.1126/science.283.5405.1183.
• Background Skok J, Poudrier J, Gray D. Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development. J Immunol. 1999 Oct 15;163(8):4284-91.
• Background McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7. doi: 10.1002/ana.1032.
• Background Pozzilli C, Bastianello S, Koudriavtseva T, Gasperini C, Bozzao A, Millefiorini E, Galgani S, Buttinelli C, Perciaccante G, Piazza G, Bozzao L, Fieschi C. Magnetic resonance imaging changes with recombinant human interferon-beta-1a: a short term study in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996 Sep;61(3):251-8. doi: 10.1136/jnnp.61.3.251.
• Romano S, Ferraldeschi M, Bagnato F, Mechelli R, Morena E, Caldano M, Buscarinu MC, Fornasiero A, Frontoni M, Nociti V, Mirabella M, Mayer F, Bertolotto A, Pozzilli C, Vanacore N, Salvetti M, Ristori G. Drug Holiday of Interferon Beta 1b in Multiple Sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority. Front Neurol. 2019 Jul 16;10:695. doi: 10.3389/fneur.2019.00695. eCollection 2019.

Drugs

Indications