Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switching.

OBJECTIVE: To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). METHOD: Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). RESULTS: AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). CONCLUSIONS: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points• Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy• Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country / Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti-TNF em um país de alto risco para tuberculose

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Resumo Objetivo: Avaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF. Métodos: Trata-se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti-TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti-TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses. Resultados: Incluíram-se 69 pacientes com AIJ com idade atual de 17,4 ± 5,8 anos, com média de duração da doença de 5 ± 4,9 anos; 47 pacientes receberam um único anti-TNF, enquanto 22 foram transferidos para outro anti-TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos). Conclusão: A avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti-TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.