Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries With Rheumatoid Arthritis Treated With Targeted Disease-Modifying Antirheumatic Agents.
JAMA Netw Open
; 5(4): e226567, 2022 04 01.
Article
em En
| MEDLINE
| ID: mdl-35394510
ABSTRACT
Importance Cytokine signaling, including tumor necrosis factor (TNF) and interleukin (IL)-6, through the Janus-kinase (JAK)-signal transducer and activator of transcription pathway, was hypothesized to attenuate the risk of Alzheimer disease and related dementia (ADRD) in the Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative based on multiomics phenotyping. Objective:
To evaluate the association between treatment with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept and risk of incident ADRD. Design, Setting, andParticipants:
This cohort study was conducted among US Medicare fee-for-service patients with rheumatoid arthritis aged 65 years and older from 2007 to 2017. Patients were categorized into 3 cohorts based on initiation of tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors compared with a common comparator abatacept (a T-cell activation inhibitor). Analyses were conducted from August 2020 to August 2021. Main Outcomes andMeasures:
The main outcome was onset of ADRD based on diagnosis codes evaluated in 4 alternative analysis schemes (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Hazard ratios (HRs) with 95% CIs were calculated from Cox proportional hazard regression after adjustment for 79 preexposure characteristics through propensity score matching.Results:
After 11 propensity score matching to patients using abatacept, a total of 22â¯569 propensity score-matched patient pairs, including 4224 tofacitinib pairs (mean [SD] age 72.19 [5.65] years; 6945 [82.2%] women), 6369 tocilizumab pairs (mean [SD] age 72.01 [5.46] years; 10â¯105 [79.4%] women), and 11â¯976 TNF inhibitor pairs (mean [SD] age 72.67 [5.91] years; 19â¯710 [82.3%] women), were assessed. Incidence rates of ADRD varied from 2 to 18 per 1000 person-years across analyses schemes. There were no statistically significant associations of ADRD with tofacitinib (analysis 1 HR, 0.90 [95% CI, 0.55-1.51]; analysis 2 HR, 0.78 [95% CI, 0.53-1.13]; analysis 3 HR, 1.29 [95% CI, 0.72-2.33]; analysis 4 HR, 0.50 [95% CI, 0.21-1.20]), tocilizumab (analysis 1 HR, 0.82 [95% CI, 0.55-1.21]; analysis 2 HR, 1.05 [95% CI, 0.81-1.35]; analysis 3 HR, 1.21 [95% CI, 0.75-1.96]; analysis 4 HR, 0.78 [95% CI, 0.44-1.39]), or TNF inhibitors (analysis 1 HR, 0.93 [95% CI, 0.72-1.20]; analysis 2 HR, 1.02 [95% CI, 0.86-1.20]; analysis 3 HR, 1.13 [95% CI, 0.86-1.48]; analysis 4 0.90 [95% CI, 0.60-1.37]) compared with abatacept. Results from prespecified subgroup analysis by age, sex, and baseline cardiovascular disease were consistent except in patients with cardiovascular disease, for whom there was a potentially lower risk of ADRD with TNF inhibitors vs abatacept, but only in analyses 2 and 4 (analysis 1 HR, 0.76 [95% CI, 0.50-1.16]; analysis 2 HR, 0.74 [95% CI, 0.56-0.99]; analysis 3 HR, 1.03 [95% CI, 0.65-1.61]; analysis 4 HR, 0.45 [95% CI, 0.21-0.98]). Conclusions and Relevance This cohort study did not find any association of risk of ADRD in patients treated with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept.
Texto completo:
1
Temas:
ECOS
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Aspectos_gerais
Bases de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Doenças Cardiovasculares
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Antirreumáticos
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
JAMA Netw Open
Ano de publicação:
2022
Tipo de documento:
Article