TY - JOUR

T1 - Risk of neuroinflammatory events in arthritis patients treated with tumour necrosis factor alpha inhibitors

T2 - a collaborative population-based cohort study from Denmark and Sweden

AU - Kopp, Tine Iskov

AU - Delcoigne, Bénédicte

AU - Arkema, Elizabeth V

AU - Jacobsen, Rikke Kart

AU - Magyari, Melinda

AU - Ibfelt, Else Helene

AU - Locht, Henning

AU - Sellebjerg, Finn

AU - Cordtz, Rene Lindholm

AU - Jensen, Dorte V

AU - Askling, Johan

AU - Dreyer, Lene

N1 - © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/5

Y1 - 2020/5

N2 - OBJECTIVES: To investigate whether tumour necrosis factor alpha inhibitors (TNFis) are associated with an increased risk of neuroinflammatory diseases among patients with arthritic diseases.METHODS: Cohorts of patients with rheumatoid arthritis (RA, n=25 796), psoriatic arthritis (PsA, n=8586) and ankylosing spondylitis (AS, n=9527) who initiated a TNFi treatment year 2000-2017 were identified from nationwide clinical rheumatology registers in Sweden and Denmark. Information on demyelinating disease and inflammatory neuropathy diagnoses was retrieved from prospective linkage to National Patients Register. A Cox proportional hazard model was used to estimate HRs and 95% CI comparing TNFi exposed and non-exposed, by disease and country.RESULTS: Among 111 455 patients with RA, we identified 270 (Sweden) and 51 (Denmark) events (all types of neuroinflammatory diseases combined), corresponding to crude incidence rates (per 1000 person-years) of 0.37 (Sweden) and 0.39 (Denmark) in TNFi-treated patients vs 0.39 (Sweden) and 0.28 (Denmark) in unexposed patients, and an age-sex-calendar-period-adjusted HR (95% CI) of 0.97 (0.72 to 1.33) (Sweden) and 1.45 (0.74 to 2.81) (Denmark) in TNFi exposed compared with non-exposed patients. For a total of 64 065 AS/PsA patients, the corresponding numbers were: 196 and 32 events, crude incidence rates of 0.59 and 0.87 in TNFi-treated patients vs 0.40 and 0.19 in unexposed patients, and HRs of 1.50 (1.07 to 2.11) and 3.41 (1.30 to 8.96), for Sweden and Denmark, respectively. For multiple sclerosis, the patterns of HRs were similar.CONCLUSIONS: Use of TNFi in AS/PsA, but not in RA, was associated with increased risk of incident neuroinflammatory disease, though the absolute risk was below one in 1000 patients/year.

AB - OBJECTIVES: To investigate whether tumour necrosis factor alpha inhibitors (TNFis) are associated with an increased risk of neuroinflammatory diseases among patients with arthritic diseases.METHODS: Cohorts of patients with rheumatoid arthritis (RA, n=25 796), psoriatic arthritis (PsA, n=8586) and ankylosing spondylitis (AS, n=9527) who initiated a TNFi treatment year 2000-2017 were identified from nationwide clinical rheumatology registers in Sweden and Denmark. Information on demyelinating disease and inflammatory neuropathy diagnoses was retrieved from prospective linkage to National Patients Register. A Cox proportional hazard model was used to estimate HRs and 95% CI comparing TNFi exposed and non-exposed, by disease and country.RESULTS: Among 111 455 patients with RA, we identified 270 (Sweden) and 51 (Denmark) events (all types of neuroinflammatory diseases combined), corresponding to crude incidence rates (per 1000 person-years) of 0.37 (Sweden) and 0.39 (Denmark) in TNFi-treated patients vs 0.39 (Sweden) and 0.28 (Denmark) in unexposed patients, and an age-sex-calendar-period-adjusted HR (95% CI) of 0.97 (0.72 to 1.33) (Sweden) and 1.45 (0.74 to 2.81) (Denmark) in TNFi exposed compared with non-exposed patients. For a total of 64 065 AS/PsA patients, the corresponding numbers were: 196 and 32 events, crude incidence rates of 0.59 and 0.87 in TNFi-treated patients vs 0.40 and 0.19 in unexposed patients, and HRs of 1.50 (1.07 to 2.11) and 3.41 (1.30 to 8.96), for Sweden and Denmark, respectively. For multiple sclerosis, the patterns of HRs were similar.CONCLUSIONS: Use of TNFi in AS/PsA, but not in RA, was associated with increased risk of incident neuroinflammatory disease, though the absolute risk was below one in 1000 patients/year.

KW - Aged

KW - Arthritis, Psoriatic/diagnosis

KW - Arthritis, Rheumatoid/diagnosis

KW - Cohort Studies

KW - Demyelinating Diseases/chemically induced

KW - Denmark

KW - Female

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Nervous System Diseases/chemically induced

KW - Prognosis

KW - Proportional Hazards Models

KW - Registries

KW - Retrospective Studies

KW - Risk Assessment

KW - Spondylitis, Ankylosing/diagnosis

KW - Sweden

KW - Tumor Necrosis Factor Inhibitors/administration & dosage

KW - Tumor Necrosis Factor-alpha/adverse effects

U2 - 10.1136/annrheumdis-2019-216693

DO - 10.1136/annrheumdis-2019-216693

M3 - Journal article

C2 - 32161058

VL - 79

SP - 566

EP - 572

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 5

ER -