Background: There is a scarcity of reports comparing efficacy and tolerability of the multiple sclerosis (MS) disease-modifying therapies [DMTs; intramuscular interferon-β1a (IM IFNβ-1a), subcutaneous (SC) IFNβ-1a, SC IFNβ-1b, SC glatiramer acetate (GA)] in a real-world setting. Methods: This multicenter, non-interventional, retrospective cohort study analyzed data from 546 patients with clinically isolated or relapsing-remitting MS constantly treated with one DMT for 2 years. Annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and DMT tolerability were assessed. Results: Demographic data were comparable across DMTs. There were no significant differences between DMT groups in ARR during study year 1 (p = 0.277) or study year 2 (p = 0.670), or in EDSS change between years 1 and 2 (p = 0.624). Adverse events were frequent (39-56%) in all groups. Flu-like symptoms were less frequent with GA treatment (2.3% vs. IM IFNβ-1a, 46.7%; SC IFNβ-1a, 39.8%; SC IFNβ-1b, 25.8%; p < 0.05). Injection site reactions were less often reported with IM IFNβ-1a (10.5% vs. SC IFNβ-1a, 33.9%; SC IFNβ-1b, 38.3%; GA, 26.1%; p < 0.05). Conclusions: All DMTs showed comparable effects on MS relapse rate and EDSS change, with IM IFNβ-1a and GA being more tolerable with respect to injection site reactions and flu-like symptoms, respectively.

Keywords:
Multiple sclerosis, Disease-modifying therapies, Swiss Analysis of Multiple Sclerosis study, Efficacy, Safety
1.
IFNB Multiple Sclerosis Study Group: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993;43:655-661.
2.
Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE 3rd, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH: Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996;39:285-294.
3.
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB: Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995;45:1268-1276.
4.
PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group: Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998;352:1498-1504.
5.
Paty DW, Li DK: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology 1993;43:662-667.
6.
Comi G, Filippi M, Wolinsky JS: European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging - measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann Neurol 2001;49:290-297.
7.
O'Connor P, Filippi M, Arnason B, Comi G, Cook S, Goodin D, Hartung HP, Jeffery D, Kappos L, Boateng F, Filippov V, Groth M, Knappertz V, Kraus C, Sandbrink R, Pohl C, Bogumil T, BEYOND Study Group, O'Connor P, Filippi M, Arnason B, Cook S, Goodin D, Harung HP, Kappos L, Jeffery D, Comi G: 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol 2009;8:889-897.
8.
Mikol DD, Barkhof F, Chang P, Coyle PK, Jeffery DR, Schwid SR, Stubinski B, Uitdehaag BM, REGARD study Group: Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 2008;7:903-914.
9.
Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O'Connor P, Monaghan E, Li D, Weinshenker B, EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) Study Group, University of British Columbia MS/MRI Research Group: Randomized, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE Trial. Neurology 2002;59:1496-506.
10.
Durelli L, Verdun E, Barbero P, Ricci A, Zhong JJ, Ferrero B, Clerico M, Pipieri A, Verdun E, Giordano L, Durelli L, INCOMIN Trial Study Group: Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 2002;359:1453-1460.
11.
Milanese C, La Mantia L, Palumbo R, Martinelli V, Murialdo A, Zaffaroni M, Caputo D, Capra R, Bergamaschi R, North Italy Multiple Sclerosis Group: A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients. J Neurol Neurosurg Psychiatry 2003;74:1689-1692.
12.
Miralles AA, Fuentes B, Barreiro P, Diez-Tejedor E: Comparative clinical efficacy analysis between interferon beta 1-b and interferon beta 1-a (abstract). J Neurol 2000;247:III139..
13.
Öztekin N, Öztekin MF: An open-label trial comparing the effects of IFNβ-1a (Rebif), (Avonex), and IFNβ-1b (Betaferon) on the relapse rate, lesion load on MRI and disease progression in patients with relapsing-remitting multiple sclerosis: results of 24 months of therapy (abstract P312). Mult Scler 2001;7(suppl 1):S96.
14.
Pakdaman H: Response to beta-interferon in Iranian multiple sclerosis patients (abstract P146). Mult Scler 2001;7(suppl 1):S54.
15.
Río J, Tintoré M, Nos C, Téllez N, Galán I, Montalban X: Interferon beta in relapsing-remitting multiple sclerosis: an eight years experience in a specialist multiple sclerosis centre. J Neurol 2005;252:795-800.
16.
Seijo-Martinez M, Amigo MC, Arias M, et al: Experience of interferon beta (INF-β) treatment in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) in Galicia (Spain) (abstract P144). Mult Scler 2001;7(suppl 1):S54.
17.
Trojano M, Liguori M, Paolicelli D, Zimatore GB, De Robertis F, Avolio C, Giuliani F, Fuiani A, Livrea P, Southern Italy MS Group: Interferon beta in relapsing-remitting multiple sclerosis: an independent postmarketing study in southern Italy. Mult Scler 2003;9:451-457.
18.
Patti F, Pappalardo A, Florio C, Politi G, Fiorilla T, Reggio E, Reggio A: Effects of interferon beta-1a and -1b over time: 6-year results of an observational head-to-head study. Acta Neurol Scand 2006;113:241-247.
19.
Limmroth V, Malessa R, Zettl UK, Koehler J, Japp G, Haller P, Elias W, Obhof W, Viehöver A, Meier U, Brosig A, Hasford J, Putzki N, Kalski G, Wernsdörfer C, QUASIMS Study Group: Quality Assessment in Multiple Sclerosis Therapy (QUASIMS): a comparison of interferon beta therapies for relapsing-remitting multiple sclerosis. J Neurol 2007;254:67-77.
20.
Khan OA, Tselis AC, Kamholz JA, Garbern JY, Lewis RA, Lisak RP: A prospective, open-label treatment trial to compare the effect of IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis: results after 18 months of therapy. Mult Scler 2001;7:349-353.
21.
Haas J, Firzlaff M: Twenty-four-month comparison of immunomodulatory treatments - a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone). Eur J Neurol 2005;12:425-431.
22.
Sorensen PS, Koch-Henriksen N, Ravnborg M, Frederiksen JL, Jensen K, Heltberg A, Schaldemose H, Deth S, Kristensen O, Worm M, Stenager E, Hansen HJ, Sivertsen B, Torring J, Danish Multiple Sclerosis Study Group: Immunomodulatory treatment of multiple sclerosis in Denmark: a prospective nationwide survey. Mult Scler 2006;12:253-264.
23.
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS: Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria'. Ann Neurol 2005;58:840-846.
24.
Derwenskus J: Current disease-modifying treatment of multiple sclerosis. Mt Sinai J Med 2011;78:161-175.
25.
Wingerchuk DM, Noseworthy JH: Randomized controlled trials to assess therapies for multiple sclerosis. Neurology 2002;58(suppl 4):S40-S48.
26.
Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000;342:1878-1886.
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2013
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