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 language | English |
|---|---|
| Journal | Seminars in Arthritis and Rheumatism |
| Volume | 48 |
| Issue number | 6 |
| Pages (from-to) | 958-966 |
| ISSN | 0049-0172 |
| DOIs | |
| Publication status | Published - 1. Jun 2019 |
| Externally published | Yes |
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Keywords
- GRADE
- JAK inhibitors
- biological agents
- biological monotherapy
- meta-analysis
- methotrexate
- rheumatoid arthritis
- systematic review
Cite this
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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 journal › Journal article › Research › peer-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 -