Immunogenicity and tolerability of an investigational formulation of interferon-β1a: 24- and 48-week interim analyses of a 2-year, single-arm, historically controlled, phase IIIb study in adults with multiple sclerosis

Clinical Therapeutics

Volumn 29, Issue 6, 2007, Pages 1128-1145

  Giovannoni, Gavin ^a   Barbarash, Olga ^b   Casset Semanaz, Florence ^c   Jaber, Amer ^c   King, John ^d   Metz, Luanne ^e   Pardo, Gabriel ^f   Simsarian, James ^g   Sørensen, Per Soelberg ^h   Stubinski, Bettina ^c  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b KEMEROVO STATE MEDICAL UNIVERSITY   (Russian Federation)

^c MERCK SERONO S A   (Switzerland)

^d ROYAL MELBOURNE HOSPITAL   (Australia)

^e UNIVERSITY OF CALGARY   (Canada)

^f NeuroScience Institute   (United States)

^g Neurology Center of Fairfax   (United States)

^h Rigshospitalet   (Denmark)

Author keywords

immunogenicty; injection site reactions; interferon 1a; neutralizing antibodies; Rebif New Formulation

Indexed keywords

ACETYLSALICYLIC ACID; BETA1A INTERFERON; DICLOFENAC; IBUPROFEN; MEPREDNISONE; NEUTRALIZING ANTIBODY; PARACETAMOL; PIRACETAM;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; CHILL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOPENIA; DEMOGRAPHY; DEPRESSION; DIZZINESS; DOSE RESPONSE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG FATALITY; DRUG FORMULATION; DRUG TOLERABILITY; EDEMA; ERYTHEMA; EVIDENCE BASED PRACTICE; EXPANDED DISABILITY STATUS SCALE; FATIGUE; FEMALE; FEVER; FLU LIKE SYNDROME; HEADACHE; HUMAN; HYPERSENSITIVITY REACTION; IMMUNOGENICITY; INFLAMMATION; INJECTION SITE DESQUAMATION; INJECTION SITE PAIN; INJECTION SITE REACTION; INTERMETHOD COMPARISON; LIVER DISEASE; MAJOR CLINICAL STUDY; MALAISE; MALE; MULTICENTER STUDY; MULTIPLE SCLEROSIS; MYALGIA; NAUSEA; NEUTROPENIA; PHASE 3 CLINICAL TRIAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; SIDE EFFECT; SKIN INDURATION; SUICIDAL IDEATION; SWELLING; THYROID DISEASE; UPPER RESPIRATORY TRACT INFECTION;

ADOLESCENT; ADULT; BIOLOGICAL RESPONSE MODIFIERS; CHEMISTRY, PHARMACEUTICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; EUROPE; FEMALE; HUMANS; INTERFERON-BETA; MALE; MIDDLE AGED; MULTIPLE SCLEROSIS; NORTH AMERICA; PROSPECTIVE STUDIES; SINGLE-BLIND METHOD; TIME FACTORS; TREATMENT OUTCOME;

EID: 34547121717     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2007.06.002     Document Type: Article

References (68)

1. www.fda.gov/cder/foi/label/2003/ifnbser050203lb.pdf
2. Avonex (interferon beta-1a). Available at:. www.fda.gov/cder/foi/label/2003/ifnbbio052803lb.pdf Accessed February 22, 2007
3. www.fda.gov/cder/foi/label/2003/ifnbchi031403lb.pdf
4. Frohman E., Phillips T., Kokel K., et al. Disease-modifying therapy in multiple sclerosis: Strategies for optimizing management. Neurologist 8 (2002) 227-236
5. for the European Beta-1a IM Dose-Comparison Study Investigators. Kappos L., Clanet M., Sandberg-Wollheim M., et al. Neutralizing antibodies and efficacy of interferon beta-1a: A 4-year controlled study. Neurology 65 (2005) 40-47
6. Giovannoni G., and Goodman A. Neutralizing anti-IFN-beta antibodies: How much more evidence do we need to use them in practice?. Neurology 65 (2005) 6-8
7. for the Danish Multiple Sclerosis Study Group. Sorensen P., Ross C., Clemmesen K., et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 362 (2003) 1184-1191
8. for the EVIDENCE Study Group. Sandberg-Wollheim M., Bever C., Carter J., et al. Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis. The EVIDENCE study. J Neurol 252 (2005) 8-13
9. for the PRISMS Study Group. Francis G., Rice G., and Alsop J. Interferon beta-1a in MS: Results following development of neutralizing antibodies in PRISMS. Neurology 65 (2005) 48-55
10. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: Experience during the first three years. Neurology 47 (1996) 889-894
11. The PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group. PRISMS-4: Long-term efficacy of interferon-beta-1a in relapsing MS [published correction appears in Neurology. 2001;57:1146]. Neurology 56 (2001) 1628-1636
12. for the Multiple Sclerosis Collaborative Research Group (MSCRG). Rudick R., Simonian N., Alam J., et al. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Neurology 50 (1998) 1266-1272
13. for the European Study Group in Interferon Beta-1b in Secondary Progressive MS. Polman C., Kappos L., White R., et al. Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology 60 (2003) 37-43
14. for the IFNB Multiple Sclerosis Study Group. Petkau A., White R., Ebers G., et al. Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis. Mult Scler 10 (2004) 126-138
15. Perini P., Calabrese M., Biasi G., and Gallo P. The clinical impact of interferon beta antibodies in relapsing-remitting MS. J Neurol 251 (2004) 305-309
16. Mohr D., Goodkin D., Likosky W., et al. Therapeutic expectations of patients with multiple sclerosis upon initiating interferon beta-1b: Relationship to adherence to treatment. Mult Scler 2 (1996) 222-226
17. Mohr D., Likosky W., Boudewyn A., et al. Side effect profile and adherence to in the treatment of multiple sclerosis with interferon beta-1a. Mult Scler 4 (1998) 487-489
18. Durelli L., and Ricci A. Anti-interferon antibodies in multiple sclerosis. Molecular basis and their impact on clinical efficacy. Front Biosci 9 (2004) 2192-2204
19. for the Danish Multiple Sclerosis Study Group. Ross C., Clemmesen K., Svenson M., et al. Immunogenicity of interferon-beta in multiple sclerosis patients: Influence of preparation, dosage, dose frequency, and route of administration. Ann Neurol 48 (2000) 706-712
20. Schellekens H. How similar do 'biosimilars' need to be?. Nat Biotechnol 22 (2004) 1357-1359
21. Schellekens H. The immunogenicity of biopharmaceuticals. Neurology 61 Suppl 5 (2003) S11-S12
22. for the Independent Comparison of Interferon (INCOMIN) Trial Study Group. Durelli L., Verdun E., Barbero P., et al. 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 359 (2002) 1453-1460
23. 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 [published correction appears in Lancet. 1999;353:678]. Lancet 352 (1998) 1498-1504
24. Panitch H. Differences between IFN beta-1a 44μg TIW and 30 μg QW sustained to 16 months: Final EVIDENCE results. Int J MS Care 5 (2003) 80
25. for the European IFNbeta-1a (Avonex) Dose-Comparison Study Investigators. Clanet M., Radue E., Kappos L., et al. A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology 59 (2002) 1507-1517
26. for the EVIDENCE (EVidence of Interferon Dose-Response: European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group. Panitch H., Goodin D., Francis G., et al. Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: Final comparative results of the EVIDENCE trial. J Neurol Sci 239 (2005) 67-74
27. for the CHAMPS Study Group. Jacobs L., Beck R., Simon J., et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 343 (2000) 898-904
28. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS: Clinical results. Neurology 56 (2001) 1496-1504
29. Antonelli G., Bagnato F., and Dianzani F. Considerations on the development of serum antibodies to interferonbeta. New Microbiol 28 (2005) 183-192
30. for the EFNS Task Force on Anti-IFN-beta Antibodies in Multiple Sclerosis. Sorensen P., Deisenhammer F., Duda P., 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 12 (2005) 817-827
31. Bertolotto A., Malucchi S., Sala A., et al. Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: A follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry 73 (2002) 148-153
32. Bertolotto A., Gilli F., Sala A., et al. Persistent neutralizing antibodies abolish the interferon beta bioavailability in MS patients. Neurology 60 (2003) 634-639
33. Bellomi F., Scagnolan C., Tomassini V., et al. Fate of neutralizing and binding antibodies to IFN beta in MS patients treated with IFN beta for 6 years. J Neurol Sci 215 (2003) 3-8
34. for the Danish Multiple Sclerosis Study Group. Sorensen P., Koch-Henriksen N., Ross C., et al. Appearance and disappearance of neutralizing antibodies during interferon-beta therapy. Neurology 65 (2005) 33-39
35. Rice G., Paszner B., Oger J., et al. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b. Neurology 52 (1999) 1277-1279
36. for the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Goodin D., Frohman E., Garmany Jr. G., et al. Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. [published correction appears in Neurology. 2002;59:480]. Neurology 58 (2002) 169-178
37. for the EVIDENCE Study Group (EVidence of Interferon Dose-Response: European North American Comparative Efficacy) and the University of British Columbia MS/MRI Research Group. Panitch H., Goodin D., Francis G., et al. Randomized comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology 59 (2002) 1496-1506
38. for the International Working Group for Treatment Optimization in MS. Karussis D., Biermann L., Bohlega S., et al. A recommended treatment algorithm in relapsing multiple sclerosis: Report of an international consensus meeting. Eur J Neurol 13 (2006) 61-71
39. Gottberg K., Gardulf A., and Fredrikson S. Interferon-beta treatment for patients with multiple sclerosis: The patients' perceptions of the side-effects. Mult Scler 6 (2000) 349-354
40. Cramer J., Cuffel B., Divan V., et al. Patient satisfaction with an injection device for multiple sclerosis treatment. Acta Neurol Scand 113 (2006) 156-162
41. Reess J., Haas J., Gabriel K., et al. Both paracetamol and ibuprofen are equally effective in managing flu-like symptoms in relapsing-remitting multiple sclerosis patients during interferon beta-1a (AVONEX) therapy. Mult Scler 8 (2002) 15-18
42. Rio J., Nos C., Bonaventura I., et al. Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: A randomized trial. Neurology 63 (2004) 525-528
43. Denis L., Namey M., Costello K., et al. Long-term treatment optimization in individuals with multiple sclerosis using disease-modifying therapies: A nursing approach. J Neurosci Nurs 36 (2004) 10-22
44. Burks J. Interferon-beta1b for multiple sclerosis [published correction appears in Expert Rev Neurother. 2005;5:428]. Expert Rev Neurother 5 (2005) 153-164
45. Jaber A., and Baker M. Assessment of the immunogenicity of different interferon beta-1a formulations using ex vivo T-cell assays. J Pharm Biomed Anal 43 (2007) 1256-1261
46. Brearley C, Jaber A, Bertolino M, et al. Assessment of the safety, tolerability, and PK/PD properties of two new formulations of subcutaneously administered IFN-β1a: A double-blind, placebo-controlled comparison with the currently available formulation. Int J Clin Pharmacol Ther. In press.
47. Bellomi F, Muto A, Palmier G, et al. Immunogenicity comparison of interferon beta-1a preparations using the BALB/c mouse model: Assessment of a new formulation for use in multiple sclerosis. New Microbiol. In press.
48. www.fda.gov/cder/guidance/959fnl.pdf
49. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Available at. www.wma.net/e/policy/b3.htm Accessed February 23, 2007.
50. Kurtzke J. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 33 (1983) 1444-1452
51. McDonald W., Compston A., Edan G., et al. Recommended diagnostic criteria for multiple sclerosis: Guide-lines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50 (2001) 121-127
52. Casoni F., Merelli E., Bedin R., et al. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?. Acta Neurol Scand 109 (2004) 61-65
53. www.meddramsso.com/msoweb/index.htm
54. WHO Adverse Reaction Terminology. Available at:. www.umcproducts.com/dynpage.aspx?id=4918mn=1107 Accessed June 1 2007
55. www.fda.gov/cder/cancer/toxicityframe.htm
56. WHO Anatomical Therapeutic Chemical Index. Available at:. www.whocc.no/atcddd Accessed June 1 2007
57. www.umcproducts.com/dynpage.aspx?id=2829mn=1107
58. Poser C., Paty D., Scheinberg L., et al. New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 13 (1983) 227-231
59. Francis G. Benefit-risk assessment of interferon-beta therapy for relapsing multiple sclerosis [published correction appears in Expert Opin Drug Saf. 2004;3:505]. Expert Opin Drug Saf 3 (2004) 289-303
60. Phillips J., Rice G., Frohman E., et al. A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis. Clin Ther 26 (2004) 511-521
61. www.emro.who.int/ncd/publications/adherence_report.pdf
62. Rio J., Porcel J., Tellez N., et al. Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis. Mult Scler 11 (2005) 306-309
63. Daugherty K., Butler J., Mattingly M., and Ryan M. Factors leading patients to discontinue multiple sclerosis therapies. J Am Pharm Assoc (Wash DC) 45 (2005) 371-375
64. Frohman E., Brannon K., Alexander S., et al. Disease modifying agent related skin reactions in multiple sclerosis: Prevention, assessment, and management. Mult Scler 10 (2004) 302-307
65. for the Rebiject Study Group. Mikol D., Lopez-Bresnahan M., Taraskiewicz S., et al. A randomized, multicentre, open-label, parallel-group trial of the tolerability of interferon beta-1a (Rebif) administered by autoinjection or manual injection in relapsing-remitting multiple sclerosis. Mult Scler 11 (2005) 585-591
66. Herndon R., Rudick R., Munschauer III F., et al. Eight-year immunogenicity and safety of interferon beta-1a-Avonex treatment in patients with multiple sclerosis. Mult Scler 11 (2005) 409-419
67. Gneiss C., Reindl M., Lutterotti A., et al. Interferon-beta: The neutralizing antibody (NAb) titre predicts reversion to NAb negativity. Mult Scler 10 (2004) 507-510
68. Sorensen P., Koch-Henriksen N., and Bendtzen K. Are ex vivo neutralizing antibodies against IFN-beta always detrimental to therapeutic efficacy in multiple sclerosis?. Mult Scler 13 (2007) 616-621