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Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials

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Tarp, Simon ; Furst, Daniel E ; Dossing, Anna ; Østergaard, Mikkel ; Lorenzen, Tove ; Hansen, Michael S ; Singh, Jasvinder A ; Choy, Ernest H ; Boers, Maarten ; Suarez-Almazor, Maria E ; Kristensen, Lars E ; Bliddal, Henning ; Christensen, Robin. / Defining the optimal biological monotherapy in rheumatoid arthritis : A systematic review and meta-analysis of randomised trials. In: Seminars in Arthritis and Rheumatism. 2017 ; Vol. 46, No. 6. pp. 699-708.

Bibtex

@article{587c60102bea4460b29babefaa928828,
title = "Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials",
abstract = "OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included {"}DMARD-na{\"i}ve{"}, and 20 {"}DMARD-Inadequate responder{"} (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.",
keywords = "Journal Article",
author = "Simon Tarp and Furst, {Daniel E} and Anna Dossing and Mikkel {\O}stergaard and Tove Lorenzen and Hansen, {Michael S} and Singh, {Jasvinder A} and Choy, {Ernest H} and Maarten Boers and Suarez-Almazor, {Maria E} and Kristensen, {Lars E} and Henning Bliddal and Robin Christensen",
note = "COPECARE",
year = "2017",
month = "6",
doi = "10.1016/j.semarthrit.2016.09.003",
language = "English",
volume = "46",
pages = "699--708",
journal = "Seminars in Arthritis and Rheumatism",
issn = "0049-0172",
publisher = "W.B./Saunders Co",
number = "6",

}

RIS

TY - JOUR

T1 - Defining the optimal biological monotherapy in rheumatoid arthritis

T2 - A systematic review and meta-analysis of randomised trials

AU - Tarp, Simon

AU - Furst, Daniel E

AU - Dossing, Anna

AU - Østergaard, Mikkel

AU - Lorenzen, Tove

AU - Hansen, Michael S

AU - Singh, Jasvinder A

AU - Choy, Ernest H

AU - Boers, Maarten

AU - Suarez-Almazor, Maria E

AU - Kristensen, Lars E

AU - Bliddal, Henning

AU - Christensen, Robin

N1 - COPECARE

PY - 2017/6

Y1 - 2017/6

N2 - OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.

AB - OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.

KW - Journal Article

U2 - 10.1016/j.semarthrit.2016.09.003

DO - 10.1016/j.semarthrit.2016.09.003

M3 - Journal article

VL - 46

SP - 699

EP - 708

JO - Seminars in Arthritis and Rheumatism

JF - Seminars in Arthritis and Rheumatism

SN - 0049-0172

IS - 6

ER -

ID: 50633777