Antibodies to Commercially Available Interferon–Beta Molecules in Multiple Sclerosis Patients Treated with Natural Interferon–Beta

Mayorga, Cristobalina; Luque, Gloria M.; Romero, Francisco Aguilar; Guerrero, R.; Blanca, Miguel; Fernández, Óscar

doi:10.1159/000024139

Cited by 6 publications

(7 citation statements)

References 3 publications

(3 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…It is a regulatory protein with anti-inflammatory, antitumor, antiviral, and cell-growth regulatory effects (4,5). Chronic administration of human IFNb (hIFNb) is an effective treatment in relapsingremitting multiple sclerosis (MS) patients (5). Three recombinant hIFNb (rhIFNb) formulations are currently on the market for the treatment of MS: Betaseron/Betaferon (rhIFNb-1b; Betaseron, Berlex Laboratories, Montville, NJ, USA; Betaferon, Schering, Berlin, Germany), Avonex (rhIFNb-1a; Biogen-Idec, Cambridge, MA, USA), and Rebif (rhIFNb-1a; Serono, Inc., Rockland, MA, USA).…”

Section: Introductionmentioning

confidence: 99%

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Development of a Transgenic Mouse Model Immune Tolerant for Human Interferon Beta

et al. 2005

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a Transgenic Mouse Model Immune Tolerant for Human Interferon Beta

et al. 2005

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“…The assay was made as previously described [17], which is a modification of the assay described by Kawade's et al [13]. Briefly, plates (Nunc, Roskilde, Denmark) were seeded with 100 µl of a line of human epidermal cells (HEP-2) at 1.5x10 5 cells/ml incubated for 24 h at 37°C, 5 % CO 2 in medium RPMI 1940 (Bio-Whittaker, Md., US) with 1 % fetal calf serum.…”

Section: Materials and Methods S Patientsmentioning

confidence: 99%

“…These NABs are the antibodies that bind to the portion of the IFN-β molecule which interacts with its receptor in the target cells, preventing the biological activity of IFN-β [19,22]. NABs have been demonstrated in 10 % of MS patients treated with human natural IFN-β [17]. Studies on antibody production during treatment with recombinant IFN-β 1a [1,3,24] or IFN-β 1b [7,14,23,28] show differences in percentage; however, because these studies have used varying methods, it is not possible to compare the immunogenic capacities of the two in treating MS.…”

mentioning

confidence: 99%

Study of binding and neutralising antibodies to interferon-? in two groups of relapsing-remitting multiple sclerosis patients

Fernández¹,

Mayorga

Luque³

et al. 2001

Journal of Neurology

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Interferon (IFN)-beta is generally considered an effective treatment for multiple sclerosis (MS); however, some patients do not respond to this therapy, possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-beta. We compared the two types of IFN-beta, the glycosylated IFN-beta1a and the non-glycosylated IFN-beta1b, as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-beta1a and 31 treated with IFN-beta1b for 1 year, using the same assay and criteria, to compare the two types of IFN-beta in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-beta1a and IFN-beta1b were determined by enzyme-linked immunosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-beta, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-beta1a and in 52 % of those treated with IFN-beta1b; NABs were found in 14% and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-beta1b molecule is more immunogenic than the IFN-beta1a molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients.

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“…Neutralizing antibodies (NAB) were measured using the assay described by Kawade [24] with modifications as reported previously [10,30]. The NAB measurements were performed at baseline and at 1, 2, 3, 6, 9, 12, 18 and 24 months.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with interferon Beta-1b and azathioprine in secondary progressive multiple sclerosis

Fernández¹,

Guerrero

Mayorga

et al. 2002

Journal of Neurology

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Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients. Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months ( p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy.

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Antibodies to Commercially Available Interferon–Beta Molecules in Multiple Sclerosis Patients Treated with Natural Interferon–Beta

Cited by 6 publications

References 3 publications

Development of a Transgenic Mouse Model Immune Tolerant for Human Interferon Beta

Development of a Transgenic Mouse Model Immune Tolerant for Human Interferon Beta

Study of binding and neutralising antibodies to interferon-? in two groups of relapsing-remitting multiple sclerosis patients

Combination therapy with interferon Beta-1b and azathioprine in secondary progressive multiple sclerosis

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