Background: The treatment for non-systemic Juvenile Idiopathic Arthritis (JIA) patients is guided by „treat to target“ principle with progressive intensification of treatment to reach optimal disease control. It is not known if patients’ adverse event (AE) profile worsens, as their treatment is intensified.

Objectives: Our goal was to report AEs of at least moderate intensity, serious AE and events of special interest (ESI) in non-systemic-JIA patients as they progressed from less intensive treatment with non-steroidal anti-inflammatory drugs (NSAIDs) to treatment with conventional synthetic and biologic DMARDs (csDMARDs/bDMARDs) with data from Pharmachild registry.

Methods: Inclusion criteria were children with non-systemic-JIA as per ILAR criteria with whole drug exposure from onset to last observation. Data was available from 1987 until December 2021. Non-systemic-JIA patients were classified according to their treatment (chosen by the treating physician) into either a “Control group” (CG) (NSAIDs±intra-articular (IA) glucocorticoids only) or a “STEP-up group” (starting with NSAIDS±IA glucocorticoids but subsequently requiring DMARDS as required for disease control): STEP-1 (NSAIDs±intra-articular glucocorticoids); STEP-2 (csDMARDs±oral glucocorticoids), and STEP-3 (bDMARDs±other medications). AEs were classified by the latest version of MedDRA dictionary (Version 23.1). Statistical analysis included descriptive statistics and Cox multivariate regression model.

Results: A total of 8052 non-systemic JIA patients (69.9% female) were included: 719 (8.95%) in CG; 7333 (91.1%) in STEP-1; 6856 (85.1%) in STEP-2 and 5052 (62.7%) in STEP-3. The most frequent JIA category was oligoarthritis (76 % in CG versus 39.1% in STEP-1). The median (IQR) duration of each treatment period was 5.54 (2.88-9.18) years: CG 2.65 (1.04-6.38), STEP-1 0.62 (0.25-1.79), STEP-2 1.59 (0.57-3.85) and STEP-3 3.13 (1.48-5.58) years. Methotrexate (94%) and Etanercept (70%) were the most frequent conventional synthetic and biologic DMARDs, respectively. AEs were seen in all groups, least frequently in STEP-1 (1.8%) and most frequently in STEP-3 (24.4%). SAEs were most common in STEP-3 (492 (8%) patients), and rare in STEP-1 (62 (0.8%) patients) and CG (6 (0.8%) patients). Infections were the most frequent AEs in all groups (Incidence rates 0.33-4.14/100 patient years), with bDMARD group having the highest rate. Gastrointestinal disorders were most frequent in STEP-2 (N, IR, 95% CI: 330, 1.81 (1.62- 2.01)), all other AEs in STEP-3. Patients treated with bDMARDs had the highest risk for development of first episodes of AE, SAE, infection and serious infection, with highest hazard ratio for serious infection (HR, 95% CI) at 19.17 (9.74- 37.74).

Conclusion: This is the first attempt to present a dynamic AE profile in a very large sample of non-systemic-JIA patients from an international pharmacovigilance registry applying a novel method of using patients as their “own controls”. Risk of AEs increased, and AE severity worsened with treatment intensification, with bDMARDs associated with a higher prevalence of AE, SAE and ESI when compared to treatment with csDMARDS or NSAIDs. The most frequent ESIs were infections.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Paivi Miettunen: None declared, Ana Rebollo Gimenez: None declared, Luca Carlini: None declared, Angela Pistorio: None declared, Violeta Panaviene: None declared, Jordi Anton: None declared, Sylvia Kamphuis: None declared, Troels Herlin: None declared, Pavla Dolezalova: None declared, Marco Cattalini: None declared, Gordana Susic: None declared, Helga Sanner: None declared, Maria Cristina Maggio: None declared, Soad Hashad: None declared, Reem Abdwani: None declared, Donato Rigante: None declared, Ana Rodriquez Lorzano: None declared, Chiara Pallotti: None declared, Joost F. Swart: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, Astra Zeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lily, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi, Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lily, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi.