Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2016

Open Access 01-12-2016 | Research article

Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis

Authors: Soo-Kyung Cho, Yoon-Kyoung Sung, Dam Kim, Soyoung Won, Chan-Bum Choi, Tae-Hwan Kim, Jae-Bum Jun, Dae-Hyun Yoo, Sang-Cheol Bae

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

Login to get access

Abstract

Background

The concerns about the development of adverse events (AEs) in elderly RA patients as a result of age-related changes in drug metabolism and the presence of comorbid illnesses are emphasizing due to increasing prevalence of rheumatoid arthritis (RA) in old age. However, they tend to be inadequately represented in RA clinical trials because of the exclusion criteria that are commonly applied. The tolerability and safety of TNF inhibitors in elderly patients have not been also evaluated in clinical practice. This study aimed to evaluate the retention rate and safety of TNF inhibitors (TNFI) in elderly RA patients.

Methods

Total 429 RA patients (838 person-years [PYs]) treated with TNFI from a retrospective biologic DMARDs registry. Patients were divided into an elderly (age ≥60 years) and a younger group (<60 years). The drug retention rates of both groups were compared using Kaplan-Meier curves. Potential predictors of TNFI discontinuation in the elderly were examined using Cox regression analysis. The incidence rate (IR) of serious adverse events (SAEs) in the elderly group was compared to that of the young group.

Results

Of the patients, 24.9 % (n = 107, 212 PYs) were in the elderly group. Regarding the retention rates of TNFI in 3 years, there was no significant difference between the elderly and younger group (p = 0.33). The major cause of discontinuation in elderly patients was AE (34.3 %), whereas that was drug ineffectiveness (41.7 %) in younger patients. Age (HR 1.09, CI 1.02-1.16) was a predictor of discontinuation, while the presence of comorbidity (HR 0.37, CI 0.15-0.91) had a protective effect against drug discontinuation in the elderly. The IR of SAEs in the elderly (6.13/100 PYs) was higher than in the younger group (5.11/100 PYs).

Conclusions

The retention rate of TNFI in the elderly was comparable with that in younger patients. The major cause of discontinuation in the elderly patients was AEs, while it was drug ineffectiveness in younger patients. The IR of SAEs in the elderly was higher than in the younger patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum. 2003;48:917–26.CrossRefPubMed Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum. 2003;48:917–26.CrossRefPubMed
2.
go back to reference Terkeltaub R, Esdaile J, Décary F, Tannenbaum H. A clinical study of older age rheumatoid arthritis with comparison to a younger onset group. J Rheumatol. 1983;10:418–24.PubMed Terkeltaub R, Esdaile J, Décary F, Tannenbaum H. A clinical study of older age rheumatoid arthritis with comparison to a younger onset group. J Rheumatol. 1983;10:418–24.PubMed
3.
go back to reference Cho SK, Sung YK, Choi CB, et al. Do patients with elderly-onset rheumatoid arthritis have severe functional disability? Semin Arthritis Rheum. 2012;42:23–31.CrossRefPubMed Cho SK, Sung YK, Choi CB, et al. Do patients with elderly-onset rheumatoid arthritis have severe functional disability? Semin Arthritis Rheum. 2012;42:23–31.CrossRefPubMed
4.
go back to reference Kaipiainen-Seppänen O, Aho K, Isomäki H, et al. Shift in the incidence of rheumatoid arthritis toward elderly patients in Finland during 1975–1990. Clin Exp Rheumatol. 1996;14:537–42.PubMed Kaipiainen-Seppänen O, Aho K, Isomäki H, et al. Shift in the incidence of rheumatoid arthritis toward elderly patients in Finland during 1975–1990. Clin Exp Rheumatol. 1996;14:537–42.PubMed
5.
go back to reference Kaipiainen-Seppanen O, Kautiainen H. Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Finland 1980–2000. J Rheumatol. 2006;33(11):2132–8.PubMed Kaipiainen-Seppanen O, Kautiainen H. Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Finland 1980–2000. J Rheumatol. 2006;33(11):2132–8.PubMed
7.
go back to reference Boots AM, Maier AB, Stinissen P, Masson P, Lories RJ, De Keyser F. The influence of ageing on the development and management of rheumatoid arthritis. Nat Rev Rheumatol. 2013;9:604–13.CrossRefPubMed Boots AM, Maier AB, Stinissen P, Masson P, Lories RJ, De Keyser F. The influence of ageing on the development and management of rheumatoid arthritis. Nat Rev Rheumatol. 2013;9:604–13.CrossRefPubMed
8.
go back to reference Radovits BJ, Fransen J, Eijsbouts A, et al. Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology (Oxford). 2009;48:906–10.CrossRef Radovits BJ, Fransen J, Eijsbouts A, et al. Missed opportunities in the treatment of elderly patients with rheumatoid arthritis. Rheumatology (Oxford). 2009;48:906–10.CrossRef
9.
go back to reference Schneeweiss S, Setoguchi S, Weinblatt ME, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007;56(6):1754–64.CrossRefPubMed Schneeweiss S, Setoguchi S, Weinblatt ME, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007;56(6):1754–64.CrossRefPubMed
10.
go back to reference Bathon JM, Fleischmann RM, Van der Heijde D, et al. Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol. 2006;33:234–43.PubMed Bathon JM, Fleischmann RM, Van der Heijde D, et al. Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol. 2006;33:234–43.PubMed
11.
go back to reference Köller MD, Aletaha D, Funovits J, Pangan A, Baker D, Smolen JS. Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients. Rheumatology (Oxford). 2009;48:1575–80.CrossRef Köller MD, Aletaha D, Funovits J, Pangan A, Baker D, Smolen JS. Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients. Rheumatology (Oxford). 2009;48:1575–80.CrossRef
12.
go back to reference Zink A, Strangfeld A, Schneider M, et al. Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials. Arthritis Rheum. 2006;54:3399–407.CrossRefPubMed Zink A, Strangfeld A, Schneider M, et al. Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials. Arthritis Rheum. 2006;54:3399–407.CrossRefPubMed
13.
go back to reference Cho SK, Sakai R, Nanki T, et al. A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan. Mod Rheumatol. 2014;24:572–9.CrossRefPubMed Cho SK, Sakai R, Nanki T, et al. A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan. Mod Rheumatol. 2014;24:572–9.CrossRefPubMed
15.
go back to reference Radovits BJ, Kievit W, Fransen J, et al. Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68:1470–3.CrossRefPubMed Radovits BJ, Kievit W, Fransen J, et al. Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68:1470–3.CrossRefPubMed
16.
go back to reference Filippini M, Bazzani C, Favalli EG, et al. Efficacy and safety of anti-tumour necrosis factor in elderly patients with rheumatoid arthritis: an observational study. Clin Rev Allergy Immunol. 2010;38:90–6.CrossRefPubMed Filippini M, Bazzani C, Favalli EG, et al. Efficacy and safety of anti-tumour necrosis factor in elderly patients with rheumatoid arthritis: an observational study. Clin Rev Allergy Immunol. 2010;38:90–6.CrossRefPubMed
17.
go back to reference Hyrich KL, Watson KD, Silman AJ, et al. Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology. 2006;45:1558–65.CrossRefPubMed Hyrich KL, Watson KD, Silman AJ, et al. Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology. 2006;45:1558–65.CrossRefPubMed
18.
go back to reference Genevay S, Finckh A, Ciurea A, et al. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;57:679–85.CrossRefPubMed Genevay S, Finckh A, Ciurea A, et al. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;57:679–85.CrossRefPubMed
19.
go back to reference Ranganath VK, Maranian P, Elashoff DA, et al. Comorbidities are associated with poorer outcomes in community patients with rheumatoid arthritis. Rheumatology. 2013;52:1809–17.CrossRefPubMedPubMedCentral Ranganath VK, Maranian P, Elashoff DA, et al. Comorbidities are associated with poorer outcomes in community patients with rheumatoid arthritis. Rheumatology. 2013;52:1809–17.CrossRefPubMedPubMedCentral
20.
go back to reference Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther. 2009;11:229.CrossRefPubMedPubMedCentral Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther. 2009;11:229.CrossRefPubMedPubMedCentral
21.
go back to reference Acurcio FA, Machado MA, Moura CS, et al. Medication persistence of DMARDs and anti-TNF agents in a cohort of patients with rheumatoid arthritis in Brazil. Arthritis Care Res (Hoboken). 2016. doi:10.1002/acr.22840 [Epub ahead of print]. Acurcio FA, Machado MA, Moura CS, et al. Medication persistence of DMARDs and anti-TNF agents in a cohort of patients with rheumatoid arthritis in Brazil. Arthritis Care Res (Hoboken). 2016. doi:10.​1002/​acr.​22840 [Epub ahead of print].
23.
go back to reference Markenson JA, Gibofsky A, Palmer WR, et al. Persistence with anti-tumor necrosis factor therapies in patients with rheumatoid arthritis: observations from the RADIUS registry. J Rheumatol. 2011;38:1273–81.CrossRefPubMed Markenson JA, Gibofsky A, Palmer WR, et al. Persistence with anti-tumor necrosis factor therapies in patients with rheumatoid arthritis: observations from the RADIUS registry. J Rheumatol. 2011;38:1273–81.CrossRefPubMed
24.
go back to reference Neubauer S, Cifaldi M, Mittendorf T, et al. Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany. Health Econ Rev. 2014;4:32.CrossRefPubMedPubMedCentral Neubauer S, Cifaldi M, Mittendorf T, et al. Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany. Health Econ Rev. 2014;4:32.CrossRefPubMedPubMedCentral
25.
go back to reference Iannone F, Gremese E, Atzeni F, et al. Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol. 2012;39:1179–84.CrossRefPubMed Iannone F, Gremese E, Atzeni F, et al. Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol. 2012;39:1179–84.CrossRefPubMed
26.
go back to reference Hyrich K, Symmons D, Watson K, Silman A. Baseline comorbidity levels in biologic and standard DMARD treated patients with rheumatoid arthritis: results from a national patient register. Ann Rheum Dis. 2006;65:895–8.CrossRefPubMed Hyrich K, Symmons D, Watson K, Silman A. Baseline comorbidity levels in biologic and standard DMARD treated patients with rheumatoid arthritis: results from a national patient register. Ann Rheum Dis. 2006;65:895–8.CrossRefPubMed
27.
go back to reference Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011;50:124–31.CrossRefPubMed Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011;50:124–31.CrossRefPubMed
28.
go back to reference Lane MA, McDonald JR, Zeringue AL, et al. TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis. Medicine. 2011;90:139–45.CrossRefPubMedPubMedCentral Lane MA, McDonald JR, Zeringue AL, et al. TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis. Medicine. 2011;90:139–45.CrossRefPubMedPubMedCentral
29.
go back to reference Toh S, Li L, Harrold LR, et al. Comparative safety of infliximab and etanercept on the risk of serious infections: does the association vary by patient characteristics? Pharmacoepidemiol Drug Saf. 2012;21:524–34.CrossRefPubMedPubMedCentral Toh S, Li L, Harrold LR, et al. Comparative safety of infliximab and etanercept on the risk of serious infections: does the association vary by patient characteristics? Pharmacoepidemiol Drug Saf. 2012;21:524–34.CrossRefPubMedPubMedCentral
30.
go back to reference Schneeweiss S, Setoguchi S, Weinblatt ME, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007;56:1754–64.CrossRefPubMed Schneeweiss S, Setoguchi S, Weinblatt ME, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007;56:1754–64.CrossRefPubMed
31.
go back to reference Widdifield J, Bernatsky S, Paterson JM, et al. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res. 2013;65:353–61.CrossRef Widdifield J, Bernatsky S, Paterson JM, et al. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res. 2013;65:353–61.CrossRef
32.
go back to reference Dreyer L, Mellemkjær L, Andersen AR, et al. Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides – a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013;72:79–82.CrossRefPubMed Dreyer L, Mellemkjær L, Andersen AR, et al. Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides – a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013;72:79–82.CrossRefPubMed
33.
go back to reference Innala L, Berglin E, Möller B, et al. Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study. Arthritis Res Ther. 2014;16:R94.CrossRefPubMedPubMedCentral Innala L, Berglin E, Möller B, et al. Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study. Arthritis Res Ther. 2014;16:R94.CrossRefPubMedPubMedCentral
Metadata
Title
Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis
Authors
Soo-Kyung Cho
Yoon-Kyoung Sung
Dam Kim
Soyoung Won
Chan-Bum Choi
Tae-Hwan Kim
Jae-Bum Jun
Dae-Hyun Yoo
Sang-Cheol Bae
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1185-6

Other articles of this Issue 1/2016

BMC Musculoskeletal Disorders 1/2016 Go to the issue