Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register.
OBJECTIVE
To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure.


METHODS
The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates.


RESULTS
Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent.


CONCLUSIONS
Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.
Department of Paediatrics, Sp 1546, Erasmus MC Sophia Children's Hospital, PO Box 2060, Rotterdam 3000 CB, The Netherlands. m.otten@erasmusmc.nl
Marieke H
MH
Otten
Femke H M
FH
Prince
Janneke
J
Anink
Rebecca
R
Ten Cate
Esther P A H
EP
Hoppenreijs
Wineke
W
Armbrust
Yvonne
Y
Koopman-Keemink
Philomine A
PA
van Pelt
Sylvia
S
Kamphuis
Simone L
SL
Gorter
Koert M
KM
Dolman
Joost F
JF
Swart
J Merlijn
JM
van den Berg
Nico M
NM
Wulffraat
Marion A J
MA
van Rossum
Lisette W A
LW
van Suijlekom-Smit
D000069594:Abatacept; D000068879:Adalimumab; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects*; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012042:Registries / Q000706:statistics & numerical data*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D000069594:Abatacept; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept