Research Article| Volume 3, ISSUE 6, P670-677, November 2014

Socio-economic aspects of the testing for antibodies in MS-patients under interferon therapy in Austria: A cost of illness study

Published:September 14, 2014DOI:


      • We analyse the cost effectiveness of routine NAb testing versus no testing in MS patients.
      • We develop a Markov model over five years, which reconstructs the clinical pathway and includes disease progression, relapse, treatment switch, etc.
      • Austrian cost data were used.
      • Model results suggest that NAb testing avoids ineffective treatment, reduces relapses and associated costs.



      According to EU-guidelines testing patients on interferon-beta (IFNb) for the presence of neutralising antibodies (NAb) is recommended; IFNb treatment efficacy of NAb-positive patients equals that of placebo-treated patients. Economic impact of NAb testing in MS patients has not been explored yet. The aim of this analysis is to estimate the impact of NAb testing in RRMS-patients on Austria׳s health-care-system.


      A decision-analytic model over 5 years was performed. The cost effectiveness of NAb testing versus no testing was evaluated. The model considers switching after relapse and withdrawal. All direct costs are based on Austrian data from 2013 and were discounted at 5% per year. The efficacy outcome measure was “relapse free”. Clinical data and resource use were determined by literature.


      Total costs for all Austrian MS-patients on IFNb-therapy with testing amount to 187,554,021€ over 5 years; without testing is 175,091,300 €. Costs per relapse avoided over 5 years were 90,075€ in the NAb testing arm, and 99,535€ in the no NAb test arm, resulting in a difference of 9460€ in favour of routine NAb testing. Considering all 3590 IFNb-treated patients 2082 relapses can be avoided in the NAb testing arm versus 1759 in the no-testing arm within 5 years. Testing for NAb leads to costs per relapse avoided of 18,015€ per year versus 19,907€ when no tests are done.


      The results suggest that NAb testing reduces relapses and associated costs.


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        • Bell C.
        • Graham J.
        • Earnshaw S.
        • Oleen-Burkey M.
        • Castelli-Haley J.
        • Johnson K.
        Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on long-term clinical data.
        J Manag Care Pharm. 2007; 13: 245-261
        • Bucher H.C.
        • Guyatt G.H.
        • Griffith L.E.
        • Walter S.D.
        The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.
        J Clin Epidemiol. 1997; 50: 683-691
      1. Bundesministerium für Gesundheit und Frauen (BMGF). Austrian DRG System (LKF); 2013.

        • Calabresi P.A.
        • Giovannoni G.
        • Confavreux C.
        • Galetta S.L.
        • Havrdova E.
        • Hutchinson M.
        • et al.
        The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL.
        Neurology. 2007; 69: 1391-1403
        • Cohen J.A.
        • Coles A.J.
        • Arnold D.L.
        • Confavreux C.
        • Fox E.J.
        • Hartung H.P.
        • et al.
        Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.
        Lancet. 2012; 380: 1819-1828
        • Coles A.J.
        • Twyman C.L.
        • Arnold D.L.
        • Cohen J.A.
        • Confavreux C.
        • Fox E.J.
        • et al.
        Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial.
        Lancet. 2012; 380: 1829-1839
        • Deisenhammer F.
        Neutralising antibodies to immunological treatments for multiple sclerosis: prevalence and impact on outcomes.
        CNS Drugs. 2009; 23: 379-396
        • Ebers C.B.
        • PRISMS Study Group
        Randomised double-blind placebo-controlled study of interferon ß-1a in relapsing/remitting multiple sclerosis.
        Lancet. 1998; 352: 1498-1504
        • Farrell R.
        • Kapoor R.
        • Leary S.
        • Rudge P.
        • Thompson A.
        • Miller D.
        • et al.
        Neutralizing anti-interferon beta antibodies are associated with reduced side effects and delayed impact on efficacy of interferon-beta.
        Mult Scler. 2008; 14: 212-218
        • Gneiss C.
        • Tripp P.
        • Reichartseder F.
        • Egg R.
        • Ehling R.
        • Lutterotti A.
        • et al.
        Differing immogenic potenal of interferon beta preparation of multiple sclerosis patients.
        Mult Scler. 2006; 12: 731-737
        • Hartung H.P.
        • Gonsette R.
        • König N.
        • Kwiecinski H.
        • Guseo A.
        • Morrissey S.P.
        • et al.
        Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
        Lancet. 2002; 360
        • Hegen H.
        • Schleiser M.
        • Gneiss C.
        • Di Pauli F.
        • Ehling R.
        • Kuenz B.
        • et al.
        Persistency of neutralizing antibodies depends on titer and interferon-beta preparation.
        Mult Scler. 2012; 18: 610-615
        • Jacobs L.D.
        • Cookfair D.L.
        • Rudick R.A.
        • Herndon R.M.
        • Richert J.R.
        • Salazar A.M.
        • et al.
        Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis.
        Ann Neurol. 1996; 39
        • Johnson K.P.
        • Brooks B.R.
        • Cohen J.A.
        • Ford C.C.
        • Goldstein J.
        • Lisak R.P.
        • et al.
        Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial.
        Neurology. 1995; 45
        • Kappos L.
        • Radue E.W.
        • O'Connor P.
        • Polman C.
        • Hohlfeld R.
        • Peter Calabresi P.
        • et al.
        A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis.
        N Engl J Med. 2010; 362: 387-401
        • Kobelt G.
        • Berg J.
        • Lindgren P.
        • Plesnilla C.
        • Baumhackl U.
        • Berger T.
        • et al.
        Costs and quality of life of multiple sclerosis in Austria.
        Eur J Health Econ. 2006; 7: S14-S23
        • Krieckaert C.L.
        • Nurmohamed M.T.
        • Wolbink G.J.
        Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner.
        Ann Rheum Dis. 2012; 71: 1914-1915
      2. NICE. Assessment of interferon-beta and glatiramer for the treatment of multiple sclerosis. 〈〉; 2000

        • Oberösterreichische Gebietskrankenkasse (OÖGKK)
        Arbeitsbehelf Honorarordnung für Ärzte für Allgemeinmedizin und Fachärzte. Oberösterreichische Gebietskrankenkasse (OÖGKK), Linz2010
        • Petkau A.J.
        • White R.A.
        • Ebers G.C.
        • Reder A.T.
        • Sibley W.A.
        • Lublin F.D.
        • et al.
        Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis.
        Mult Scler. 2004; 10: 126-138
        • Plasencia C.
        • Pascual-Salcedo D.
        • Nuño L.
        • Bonilla G.
        • Villalba A.
        • Peiteado D.
        • et al.
        Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab.
        Ann Rheum Dis. 2012; 71: 1955-1960
        • Polman C.H.
        • OConnor P.W.
        • Havrdova E.
        • Hutchinson M.
        • Kappos L.
        • Miller D.H.
        • et al.
        A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.
        N Engl J Med. 2006; 354
        • Polman C.H.
        • Bertolotto A.
        • Deisenhammer F.
        • Giovannoni G.
        • Hartung H.P.
        • Hemmer B.
        • et al.
        Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis.
        Lancet Neurol. 2010; 9: 740-750
        • Pugliatti M.
        • Rosati G.
        • Carton H.
        • Riise T.
        • Drulovic J.
        • Vécsei L.
        • et al.
        The epidemiology of multiple sclerosis in Europe.
        Eur J Neurol. 2006; 13: 700-722
      3. PVA. Österreichische Pensionsversicherungsanstalt, oral communication; 2006

        • Rio J.
        • Lee J.C.
        • Simon J.
        • Ransohoff R.M.
        • Fisher E.
        Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients.
        Ann Neurol. 2006; 59: 344-352
      4. Selbstzahlerkatalog Tirol. Leistungs-und Gebührenkatalog über die Ambulanzgebühren in den öffentlichen Krankenanstalten; 2006.

      5. Selbstzahlerkatalog Wien. Festsetzung der Ambulatoriumsbeiträge für die Wiener städtischen Krankenanstalten; 2006.

        • Sibley W.A.
        • Ebers G.
        • Panitch H.S.
        • Reder A.T.
        • The IFNB Multiple Sclerosis Study Group
        Interferon beta-1-b is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial.
        Neurology. 1993; 43: 655-661
        • Sorensen P.S.
        • Deisenhammer F.
        • Duda P.
        • Hohlfeld R.
        • Myhr K.M.
        • Palace J.
        • et al.
        Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS task force on IFN-beta antibodies in multiple sclerosis.
        Eur J Neurol. 2005; 12: 817-827
      6. Statistik Austria. Death causes; 2011.

      7. Steiermärkische Gebietskrankenkasse (STGKK). Satzung 2003 der Steiermärkischen Gebietskrankenkasse; 2011.

      8. Tiroler Gebietskrankenkasse (TGKK). Honorarordnung für Ärzte für Allgemeinmedizin und Fachärzte; 2010.

        • Walter
        Österreichische guidelines zur gesundheitsökonomischen evaluation.
        PharmacoEcon – Ger Res Artic. 2006; 4: 55-63
      9. Österreichischer Apothekerverlag. Warenverzeichnis I (Austrian Kodex of Pharmaceuticals), June 2013.

        • Wiendl H.
        • Toyka K.V.
        • Rieckmann P.
        • Gold R.
        Multiple Sclerosis Therapy Consensus Group (MSTCG). Basic and escalating immunomodulatory treatments in multiple sclerosis: current therapeutic recommendations.
        J Neurol. 2008; 255: 1449-1463
      10. Wiener Gebietskrankenkasse (WGKK). Tarife für Vertragsärzte, Wien. 2011.