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Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis?: An analysis of the British Society for Rheumatology Biologics Register.

Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis?: An analysis of the British Society for Rheumatology Biologics Register.
Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis?: An analysis of the British Society for Rheumatology Biologics Register.
Objective To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults. Methods Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination. Results The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06–1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05–1.17) vs ≥75 [HR 1.13 (0.90–1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43–0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02–1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses. Conclusion TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.
1462-0324
2563 - 2571
Bechman, Katie
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Oke, Anuoluwapo
fac1b28e-b80a-41d7-aa35-e322f7f73f97
Yates, Mark
c2aaab7c-fbc0-479d-a8f2-ec6649d60656
Norton, Sam
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Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Cope, Andrew P.
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Galloway, James B.
0ae0c78a-af28-4692-8fce-5d988305eec0
Bechman, Katie
9c3687a5-cf12-49c0-883e-7ee7456f31e6
Oke, Anuoluwapo
fac1b28e-b80a-41d7-aa35-e322f7f73f97
Yates, Mark
c2aaab7c-fbc0-479d-a8f2-ec6649d60656
Norton, Sam
e6b46b72-037d-4225-a71f-119973d37a23
Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Cope, Andrew P.
73f1ca2c-9c60-43b2-988d-115cfb0e02ab
Galloway, James B.
0ae0c78a-af28-4692-8fce-5d988305eec0

Bechman, Katie, Oke, Anuoluwapo, Yates, Mark, Norton, Sam, Dennison, Elaine, Cope, Andrew P. and Galloway, James B. (2020) Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis?: An analysis of the British Society for Rheumatology Biologics Register. Rheumatology, 2563 - 2571.

Record type: Article

Abstract

Objective To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults. Methods Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination. Results The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06–1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05–1.17) vs ≥75 [HR 1.13 (0.90–1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43–0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02–1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses. Conclusion TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.

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REDO amended Monotherapy in elderly final 3 - Accepted Manuscript
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Accepted/In Press date: 9 December 2019
Published date: 29 January 2020

Identifiers

Local EPrints ID: 450262
URI: http://eprints.soton.ac.uk/id/eprint/450262
ISSN: 1462-0324
PURE UUID: b1192f80-013e-41f3-8f51-8ec431610f4a
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961

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Date deposited: 19 Jul 2021 16:37
Last modified: 28 Apr 2022 04:57

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Contributors

Author: Katie Bechman
Author: Anuoluwapo Oke
Author: Mark Yates
Author: Sam Norton
Author: Elaine Dennison ORCID iD
Author: Andrew P. Cope
Author: James B. Galloway

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