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Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab

BACKGROUND: Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently s...

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Autores principales: van Rhee, Frits, Rothman, Margaret, Ho, Kai Fai, Fleming, Sarah, Wong, Raymond S., Fosså, Alexander, Dispenzieri, Angela, Cavet, James, Munshi, Nikhil, Vermeulen, Jessica, Casper, Corey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383814/
https://www.ncbi.nlm.nih.gov/pubmed/25736164
http://dx.doi.org/10.1007/s40271-015-0120-5
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author van Rhee, Frits
Rothman, Margaret
Ho, Kai Fai
Fleming, Sarah
Wong, Raymond S.
Fosså, Alexander
Dispenzieri, Angela
Cavet, James
Munshi, Nikhil
Vermeulen, Jessica
Casper, Corey
author_facet van Rhee, Frits
Rothman, Margaret
Ho, Kai Fai
Fleming, Sarah
Wong, Raymond S.
Fosså, Alexander
Dispenzieri, Angela
Cavet, James
Munshi, Nikhil
Vermeulen, Jessica
Casper, Corey
author_sort van Rhee, Frits
collection PubMed
description BACKGROUND: Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments. METHODS: We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD–Symptom Scale (MCD–SS), the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments. RESULTS: At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD–SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD–SS and FACIT–Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health. CONCLUSIONS: Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40271-015-0120-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-43838142015-04-08 Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab van Rhee, Frits Rothman, Margaret Ho, Kai Fai Fleming, Sarah Wong, Raymond S. Fosså, Alexander Dispenzieri, Angela Cavet, James Munshi, Nikhil Vermeulen, Jessica Casper, Corey Patient Original Research Article BACKGROUND: Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments. METHODS: We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD–Symptom Scale (MCD–SS), the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments. RESULTS: At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD–SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD–SS and FACIT–Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health. CONCLUSIONS: Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40271-015-0120-5) contains supplementary material, which is available to authorized users. Springer International Publishing 2015-03-04 2015 /pmc/articles/PMC4383814/ /pubmed/25736164 http://dx.doi.org/10.1007/s40271-015-0120-5 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by-nc/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Research Article
van Rhee, Frits
Rothman, Margaret
Ho, Kai Fai
Fleming, Sarah
Wong, Raymond S.
Fosså, Alexander
Dispenzieri, Angela
Cavet, James
Munshi, Nikhil
Vermeulen, Jessica
Casper, Corey
Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title_full Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title_fullStr Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title_full_unstemmed Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title_short Patient-reported Outcomes for Multicentric Castleman’s Disease in a Randomized, Placebo-controlled Study of Siltuximab
title_sort patient-reported outcomes for multicentric castleman’s disease in a randomized, placebo-controlled study of siltuximab
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383814/
https://www.ncbi.nlm.nih.gov/pubmed/25736164
http://dx.doi.org/10.1007/s40271-015-0120-5
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