Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA).
OBJECTIVE
Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited.


OBJECTIVE
To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment.


METHODS
Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation.


METHODS
We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX).


RESULTS
Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY).


CONCLUSIONS
Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort.
German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Institute for Social Medicine, Epidemiology and Health Economics, Berlin, Germany.
Jens
http://orcid.org/0000-0002-2954-5755
J
Klotsche
German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany.
Martina
M
Niewerth
German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany.
Johannes-Peter
JP
Haas
Professor Hess Children's Hospital, Bremen, Germany.
Hans-Iko
HI
Huppertz
German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany.
Angela
A
Zink
Asklepios Kinderklinik Sankt Augustin GmbH, Sankt Augustin, Germany.
Gerd
G
Horneff
German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Children's university hospital, Berlin, Germany.
Kirsten
K
Minden
D000068879:Adalimumab / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000453:epidemiology; D001327:Autoimmune Diseases / Q000139:chemically induced; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D000068800:Etanercept / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D009894:Opportunistic Infections / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies; D012042:Registries; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014605:Uveitis / Q000139:chemically induced / Q000453:epidemiology
D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate
Autoimmune Diseases; DMARDs (biologic); Infections; Juvenile Idiopathic Arthritis; Methotrexate