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Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials

OBJECTIVE: Anti–tumor necrosis factor (anti‐TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti‐TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA pa...

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Autores principales: Combe, Bernard, Furst, Daniel E., Keystone, Edward C., van der Heijde, Désirée, Luijtens, Kristel, Ionescu, Lucian, Goel, Niti, Emery, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067694/
https://www.ncbi.nlm.nih.gov/pubmed/26238672
http://dx.doi.org/10.1002/acr.22676
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author Combe, Bernard
Furst, Daniel E.
Keystone, Edward C.
van der Heijde, Désirée
Luijtens, Kristel
Ionescu, Lucian
Goel, Niti
Emery, Paul
author_facet Combe, Bernard
Furst, Daniel E.
Keystone, Edward C.
van der Heijde, Désirée
Luijtens, Kristel
Ionescu, Lucian
Goel, Niti
Emery, Paul
author_sort Combe, Bernard
collection PubMed
description OBJECTIVE: Anti–tumor necrosis factor (anti‐TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti‐TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. METHODS: A pre‐specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment‐emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week. RESULTS: A total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28‐ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups. CONCLUSION: CZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy.
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spelling pubmed-50676942016-11-01 Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials Combe, Bernard Furst, Daniel E. Keystone, Edward C. van der Heijde, Désirée Luijtens, Kristel Ionescu, Lucian Goel, Niti Emery, Paul Arthritis Care Res (Hoboken) Rheumatoid Arthritis OBJECTIVE: Anti–tumor necrosis factor (anti‐TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti‐TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. METHODS: A pre‐specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment‐emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week. RESULTS: A total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28‐ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups. CONCLUSION: CZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy. John Wiley and Sons Inc. 2016-02-23 2016-03 /pmc/articles/PMC5067694/ /pubmed/26238672 http://dx.doi.org/10.1002/acr.22676 Text en © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Rheumatoid Arthritis
Combe, Bernard
Furst, Daniel E.
Keystone, Edward C.
van der Heijde, Désirée
Luijtens, Kristel
Ionescu, Lucian
Goel, Niti
Emery, Paul
Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title_full Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title_fullStr Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title_full_unstemmed Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title_short Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
title_sort certolizumab pegol efficacy across methotrexate regimens: a pre‐specified analysis of two phase iii trials
topic Rheumatoid Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067694/
https://www.ncbi.nlm.nih.gov/pubmed/26238672
http://dx.doi.org/10.1002/acr.22676
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