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Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study

Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active F...

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Autores principales: Henes, Joerg C., Saur, Sebastian, Kofler, David M., Kedor, Claudia, Meisner, Christoph, Schuett, Marion, Krusche, Martin, Koetter, Ina, Xenitidis, Theodoros, Schulze-Koops, Hendrik, Feist, Eugen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500594/
https://www.ncbi.nlm.nih.gov/pubmed/36143006
http://dx.doi.org/10.3390/jcm11185360
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author Henes, Joerg C.
Saur, Sebastian
Kofler, David M.
Kedor, Claudia
Meisner, Christoph
Schuett, Marion
Krusche, Martin
Koetter, Ina
Xenitidis, Theodoros
Schulze-Koops, Hendrik
Feist, Eugen
author_facet Henes, Joerg C.
Saur, Sebastian
Kofler, David M.
Kedor, Claudia
Meisner, Christoph
Schuett, Marion
Krusche, Martin
Koetter, Ina
Xenitidis, Theodoros
Schulze-Koops, Hendrik
Feist, Eugen
author_sort Henes, Joerg C.
collection PubMed
description Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be >2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial.
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spelling pubmed-95005942022-09-24 Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study Henes, Joerg C. Saur, Sebastian Kofler, David M. Kedor, Claudia Meisner, Christoph Schuett, Marion Krusche, Martin Koetter, Ina Xenitidis, Theodoros Schulze-Koops, Hendrik Feist, Eugen J Clin Med Article Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be >2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial. MDPI 2022-09-13 /pmc/articles/PMC9500594/ /pubmed/36143006 http://dx.doi.org/10.3390/jcm11185360 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Henes, Joerg C.
Saur, Sebastian
Kofler, David M.
Kedor, Claudia
Meisner, Christoph
Schuett, Marion
Krusche, Martin
Koetter, Ina
Xenitidis, Theodoros
Schulze-Koops, Hendrik
Feist, Eugen
Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title_full Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title_fullStr Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title_full_unstemmed Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title_short Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study
title_sort tocilizumab for the treatment of familial mediterranean fever—a randomized, double-blind, placebo-controlled phase ii study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500594/
https://www.ncbi.nlm.nih.gov/pubmed/36143006
http://dx.doi.org/10.3390/jcm11185360
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