AB0947 TREATMENT WITH SIMULTANEOUS BIOLOGICAL AGENTS IN JUVENILE IDIOPATHIC ARTHRITIS: SINGLE-CENTER CASE SERIES AND REVIEW OF LITERATURE
Authors: Natalia Cabrera, Pauline Nakhleh, Marine Desjonqueres, Jean-Paul Larbre, Alexandre Belot, Jean-Christophe Lega
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Several therapeutic choices are currently available for juvenile idiopathic arthritis (JIA) patients. The classical first line therapies are NSAIDs and corticosteroids (CTCs) and the second line encompasses synthetical and biological DMARDs. The clinical efficacy of DMARDs (alone or in combination) has been well demonstrated in RCTs and the treatment is often tailored on an individual basis. Combination of bDMARDs has not been formally evaluated in rheumatology and few publications are available concerning the combination of bDMARDs in patients with severe active forms of JIA, mainly systemic [SoJIA] and polyarticular [PA] categories. (1) <h3>Objectives</h3> To describe efficacy and safety of JIA patients resistant to MTX and bDMARDs requiring a simultaneous bDMARDs treatment. <h3>Methods</h3> Retrospective analysis of 7 (4.7 ± 2.1 years, male sex 75%) patients with JIA of a single tertiary center. A systematic review of literature was made to search observational studies from MEDLINE database (January 1946 to January 2019). <h3>Results</h3> All patients in the Paediatric Rheumatology Department (Lyon University Hospital) receiving combination therapy with bDMARDs were eligible. Seven patients with JIA diagnosis (4 SoJIA and 3 PA) were included. Genetic studies were performed in three patients, with positive LACC1 mutation in one. The exposure to the bDMARDs of the whole cohort was 79 patient-years (PY), including 16.5 PY of combination with simultaneous bDMARDs. The delay between the date of diagnosis and the first prescription of a combination of simultaneous bDMARDs treatment was 8.3 ± 4.8 years. Nine bDMARDs drugs were prescribed: anti-TNFs, tocilizumab and rituximab (nine times each). Ten co-prescriptions of the bDMARDs were administrated with 5 possible types of combinations between them, the most frequent associating tocilizumab/rituximab. Rituximab was used most frequently in combination with another bDMARD. The rituximab schedule was different between patients. Disease activity decreased for all patients, primarily at the biological level without reaching complete clinical remission. In general, the clinical tolerance to the co-prescription of bDMARDs was acceptable. One patient (P2) experienced a severe hepatitis event in adulthood attributed to the treatment (tocilizumab), dropping the bDMARDs combination. During the exposure time, the most frequent adverse events were infections: repeated otitis media (P1), persisting vaginitis and fungal urinary infection (P3) not requiring hospitalization. One patient (P6) had 2 episodes of purpuric rash on the days of the canakinumab injection requiring oral CTC treatment. No severe acute reactions were found and no patients died. The systematic review found a publication: retrospective series of 4 patients (SoJIA) combining abatacept and canakinumab (2). <h3>Conclusion</h3> Severe forms of JIA that are refractory to the current therapeutic options available could benefit from the combination of bDMARDs. The combination of bDMARDs may be an alternative therapy to explore in this group of patients. <h3>References</h3> [1] Cimaz R, Marino A, Martini A. How I treat juvenile idiopathic arthritis: A state of the art review. Autoimmun Rev. 2017Oct;16(10):1008–15. [2] Record JL, Beukelman T, Cron RQ. Combination Therapy of Abatacept and Anakinra in Children with Refractory Systemic Juvenile Idiopathic Arthritis: A Retrospective Case Series. J Rheumatol. 2011Jan;38(1):180–1. <h3>Acknowledgement</h3> Sincere thanks to Dr. Maria-Luisa Cabañas (INCAN, Ministry of Health of Paraguay) <h3>Disclosure of Interests</h3> None declared