Effectiveness of glatiramer acetate in neutralizing antibody-positive patients previously treated with interferon-β.

Effectiveness Glatiramer acetate Multiple sclerosis Neutralizing antibodies Real-world evidence

Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Apr 2020
Historique:
received: 15 10 2019
revised: 30 11 2019
accepted: 14 12 2019
medline: 31 12 2019
pubmed: 31 12 2019
entrez: 30 12 2019
Statut: ppublish

Résumé

Some patients with multiple sclerosis who are treated with interferon-β(IFNβ) develop neutralizing antibodies (NAbs), which reduce or abolish the therapeutic effects of the treatment. These patients are usually switched to a non-IFNβ treatment, such as glatiramer acetate (GA). It is unknown whether a patient's previous disease activity in combination with their NAb-status can provide further insights on their risk of future disease activity. Consequently, we investigated treatment outcomes in patients switching from IFNβ to GA according to NAb-status and clinical disease activity, while on IFNβ. We identified all patients switching from IFNβ to GA and having information on NAb-status from the Danish Multiple Sclerosis Registry and compared treatment outcomes while on GA according to previous disease activity and the presence of NAbs. We included 568 patients in the study: 107 NAb-negative patients switched due to adverse events (group 1), 24 NAb-negative patients switched with disease activity (group 2), 397 NAb-positive patients switched without disease activity (group 3) and 40 NAb-positive patients switched with disease activity (group 4). Compared to the reference (group 1), group 2 had an increased risk of future relapses (HR 1.79 95% Confidence interval (CI): 1.00-3.19). Group 3 showed a trend of a lower risk of future relapses (HR 0.74, 95%CI: 0.53-1.04). Group 4 had, on average, a similar risk of future relapses (HR 1.15 95% CI: 0.69-1.92). Similarly, group 2 had a higher probability of treatment discontinuation due to disease activity compared to the other groups. While on GA, patients switched from IFNβ in the context of disease activity and no NAbs had the highest risk of future disease activity, while NAb positive patients without previous activity had the lowest. We did not find any average difference between NAb-positive patients switching in a context of disease activity and NAb-negative patients switched due to adverse events, although carefulness in the interpretation of this result is advised.

Sections du résumé

BACKGROUND BACKGROUND
Some patients with multiple sclerosis who are treated with interferon-β(IFNβ) develop neutralizing antibodies (NAbs), which reduce or abolish the therapeutic effects of the treatment. These patients are usually switched to a non-IFNβ treatment, such as glatiramer acetate (GA). It is unknown whether a patient's previous disease activity in combination with their NAb-status can provide further insights on their risk of future disease activity. Consequently, we investigated treatment outcomes in patients switching from IFNβ to GA according to NAb-status and clinical disease activity, while on IFNβ.
METHODS METHODS
We identified all patients switching from IFNβ to GA and having information on NAb-status from the Danish Multiple Sclerosis Registry and compared treatment outcomes while on GA according to previous disease activity and the presence of NAbs.
RESULTS RESULTS
We included 568 patients in the study: 107 NAb-negative patients switched due to adverse events (group 1), 24 NAb-negative patients switched with disease activity (group 2), 397 NAb-positive patients switched without disease activity (group 3) and 40 NAb-positive patients switched with disease activity (group 4). Compared to the reference (group 1), group 2 had an increased risk of future relapses (HR 1.79 95% Confidence interval (CI): 1.00-3.19). Group 3 showed a trend of a lower risk of future relapses (HR 0.74, 95%CI: 0.53-1.04). Group 4 had, on average, a similar risk of future relapses (HR 1.15 95% CI: 0.69-1.92). Similarly, group 2 had a higher probability of treatment discontinuation due to disease activity compared to the other groups.
CONCLUSION CONCLUSIONS
While on GA, patients switched from IFNβ in the context of disease activity and no NAbs had the highest risk of future disease activity, while NAb positive patients without previous activity had the lowest. We did not find any average difference between NAb-positive patients switching in a context of disease activity and NAb-negative patients switched due to adverse events, although carefulness in the interpretation of this result is advised.

Identifiants

DOI: 10.1016/j.msard.2019.101894 PMID: 31884382
pubmed: 31884382
pii: S2211-0348(19)30965-4
doi: 10.1016/j.msard.2019.101894
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101894

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Buron has received support for congress participation from Roche. Dr. Magyari has served on scientific advisory board for Biogen, Sanofi, Teva, Roche,  Novartis, Merck, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, has received support for congress participation from Biogen, Genzyme, Teva, Roche. Dr. Chalmer has received support for congress participation from Merck, Novartis, Biogen, and Roche. Dr. Sorensen has received personal compensation for serving on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; and has received speaker honoraria from Biogen, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. Dr. Sellebjerg has served on scientific advisory boards, been on the steering committees of clinical trials, served as a consultant, received support for congress participation, received speaker honoraria, or received research support for his laboratory from Biogen, EMD Serono, Merck, Novartis, Roche, Sanofi Genzyme, and Teva.

Auteurs

Mathias Due Buron (MD)

Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, 2600 Glostrup, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Valdemar Hansens Vej 2, 2600 Glostrup, Denmark. Electronic address: mathias.buron@regionh.dk.

Melinda Magyari (M)

Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, 2600 Glostrup, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Valdemar Hansens Vej 2, 2600 Glostrup, Denmark. Electronic address: melinda.magyari.01@regionh.dk.

Thor Ameri Chalmer (TA)

Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, 2600 Glostrup, Denmark; Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Valdemar Hansens Vej 2, 2600 Glostrup, Denmark. Electronic address: thor.ameri.chalmer.01@regionh.dk.

Per Soelberg Sørensen (PS)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Valdemar Hansens Vej 2, 2600 Glostrup, Denmark. Electronic address: Per.Soelberg.Soerensen@regionh.dk.

Finn Sellebjerg (F)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Valdemar Hansens Vej 2, 2600 Glostrup, Denmark. Electronic address: finn.thorup.sellebjerg@regionh.dk.

Classifications MeSH