g!! Multiple Sclerosis (1996) 1, 317-320 0 1996 Stockton Press All rights reserved 1352-4585/96 $12.00 Interferon beta treatment in multiple sclerosis: the European clinical trials G Comi, V Marfinelli and M Filippi S Raffaele MS Centre, Department of Neurology, University of Milan Keywords: multiple sderosis; interferon beto; dinicol fiols; MN introduction T~VO large multicentre clinical trials performed in North Ameri~a~.~,'' demonstrated that Interferons beta (IFNS~) reduce both clinical and Magnetic Resonance haging (MRI) activities in patients with relapsing- remitting multiple sclerosis (RR-MS). Positive effects on disability were shown in the IFNP-la trial: while no significant effects on this parameter emerged in the IFNP-lb trial." In contrast a significant reduction of the T, lesion load accumulated during the trial in the treated group compared to the placebo group was observed with IFNP-lb but not with IFNP-la. In both studies clinical benefits were modest but the con- comitant effects on MRI parameters supported the efficacy of IFNP in MS since some recent transversal and longitudinal ~tudies,4.'**'~ demonstrated a correla- tion between clinical and h4RI parameters. The Food and Drug Administration in USA and the Agency for the Evaluation of Medicinal Products in European Community approved the IFNP-lb (Betaseron, Berlex- Schering) for the treatment of patients with RR-MS and are actually evaluating the documentation concerning safety and efficacy of IFNP-la (Avonex, Biogen) in MS. There is a general consensus among neurologists that IFNP is a relevant step in the therapy of MS but many questions are still opened. To answer some of these questions new clinical trials are ongoing in North America and Europe. This review concerns the clinical trials planned, in progress or recently completed in European countries, focusing on design, status and objectives of the studies. In addition, the results of the already completed trials will be shortly discussed. Four different types of IFNsP are actually available as listed in Table 1. There are differences among these molecules in structure and methods of production and purification which might determine differences in specific activity, tolerability, antibody formation and route of administration. All these molecules have been or are utilized in clinical trials performed in order to assess their efficacy in MS patients. These trials are listed in Table 2. Two trials have been completed and results have been presented at scientific meetings;zJ both have not been published yet. Five multicentre international studies are ongoing: the inclusion phase have been completed in four and just started in the fifth. One other multicentre international study have been planned and the inclusion phase will start at the Correspondence: Giancarlo Comi beginning of 1996. Other national studies will be probably performed in some European countries (Italy, Sweden, UK) under the control of local health autho- rities. Completed studies Fernandez et aL2 evaluated the efficacy and safety of natural IFNP (Frone, Ares-Serono) in a multicentre, prospective, randomized, phase II trial. Sixty RR-MS patients were randomized into two equal groups: one group was treated with natural IFNP, 9 MIU three times a week, subcutaneously, the other group was Table 1 Beta interferons Commercial Pharmaceutical Molecule name company human IFNP Frone Ares-Serono recombinant IFNP-la Rebif Ares-Serono recombinant IFNP-la Avonex Biogen recombinant IFNP-lb Betaseron Berlex-Schering Table 2 European clinical trials testing the efficacy of IFNsP in MS Molecule Drug Type of MS Status nIFNV rIFNp-lab rIFNP-la rIFNP-la rIFNP-la rIFNP-la rIFNP-lb rIFNP-la Frone (Ares- Serono) Rebif (Ares- Serono) Rebif (Ares- Serono) Rebif (Ares- Serono) (Biogen) Rebif [Ares- Serono) Betaseron (Schering) Rebif [Ares- Serono) Avonex RR" RR RR RR RR SPd SP Early" Completed Completed Accrual closed Accrual closed Planned Accrual closed Accrual closed Accrual on- going WFNP: natural interferon beta; brIFNP: recombinant inter- feron beta; "RR: relapsing remitting; dSP: secondary pro- gressive; "Early patients with a first attack suggestive of MS.