Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients

A systematic review and meta-analysis of randomised trials

Simon Tarp, Tanja S Jørgensen, Daniel E Furst, Anna Dossing, Peter C Taylor, Ernest H Choy, Maria E Suarez-Almazor, Anne Lyddiatt, Lars E Kristensen, Henning Bliddal, Robin Christensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).

METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.

RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.

CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

Original languageEnglish
JournalSeminars in Arthritis and Rheumatism
Volume48
Issue number6
Pages (from-to)958-966
ISSN0049-0172
DOIs
Publication statusPublished - 1. Jun 2019
Externally publishedYes

Fingerprint

Methotrexate
Meta-Analysis
Interleukin 1 Receptor Antagonist Protein
MEDLINE
Odds Ratio
Confidence Intervals
Safety

Keywords

  • GRADE
  • JAK inhibitors
  • biological agents
  • biological monotherapy
  • meta-analysis
  • methotrexate
  • rheumatoid arthritis
  • systematic review

Cite this

Tarp, Simon ; Jørgensen, Tanja S ; Furst, Daniel E ; Dossing, Anna ; Taylor, Peter C ; Choy, Ernest H ; Suarez-Almazor, Maria E ; Lyddiatt, Anne ; Kristensen, Lars E ; Bliddal, Henning ; Christensen, Robin. / Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients : A systematic review and meta-analysis of randomised trials. In: Seminars in Arthritis and Rheumatism. 2019 ; Vol. 48, No. 6. pp. 958-966.
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title = "Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials",
abstract = "OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95{\%} confidence intervals and the GRADE approach was used to assess confidence in the estimates.RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32{\%} better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20{\%} increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.",
keywords = "GRADE, JAK inhibitors, biological agents, biological monotherapy, meta-analysis, methotrexate, rheumatoid arthritis, systematic review",
author = "Simon Tarp and J{\o}rgensen, {Tanja S} and Furst, {Daniel E} and Anna Dossing and Taylor, {Peter C} and Choy, {Ernest H} and Suarez-Almazor, {Maria E} and Anne Lyddiatt and Kristensen, {Lars E} and Henning Bliddal and Robin Christensen",
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Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients : A systematic review and meta-analysis of randomised trials. / Tarp, Simon; Jørgensen, Tanja S; Furst, Daniel E; Dossing, Anna; Taylor, Peter C; Choy, Ernest H; Suarez-Almazor, Maria E; Lyddiatt, Anne; Kristensen, Lars E; Bliddal, Henning; Christensen, Robin.

In: Seminars in Arthritis and Rheumatism, Vol. 48, No. 6, 01.06.2019, p. 958-966.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients

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

AU - Tarp, Simon

AU - Jørgensen, Tanja S

AU - Furst, Daniel E

AU - Dossing, Anna

AU - Taylor, Peter C

AU - Choy, Ernest H

AU - Suarez-Almazor, Maria E

AU - Lyddiatt, Anne

AU - Kristensen, Lars E

AU - Bliddal, Henning

AU - Christensen, Robin

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

AB - OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

KW - GRADE

KW - JAK inhibitors

KW - biological agents

KW - biological monotherapy

KW - meta-analysis

KW - methotrexate

KW - rheumatoid arthritis

KW - systematic review

U2 - 10.1016/j.semarthrit.2018.10.002

DO - 10.1016/j.semarthrit.2018.10.002

M3 - Journal article

VL - 48

SP - 958

EP - 966

JO - Seminars in Arthritis and Rheumatism

JF - Seminars in Arthritis and Rheumatism

SN - 0049-0172

IS - 6

ER -