MATCHED CONTROLLED SURVEILLANCE OF TOCILIZUMAB TREATMENT FOR POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS-AN INTERIM ANALYSIS

Background:Tocilizumab (TOC) is approved for treatment of polyarticular juvenile idiopathic arthritis (pJIA). Data out of clinical practice are limited.Objectives:Long-term surveillance of patients initiating TOC treatment compared to a cohort of patients initiating a comparator biologic using the BIKER-registry.Methods:Baseline parameters, efficacy and safety parameters were compared. Efficacy outcomes were JADAS10 and joint counts. Functional status was determined with the Childhood Health Assessment Questionnaire disability-index (CHAQ-DI). Safety was assessed by adverse events (AE) reports.Results:Until January 2020, 152 patients have been recruited to each cohort. Patients starting on TOC were older at treatment start (12.1 vs. 10.1 years (y); p<0.0001) and had a longer disease duration (5.4y vs. 3.0y; p<0.0001). TOC was significantly more often a second-line biologic (84% vs 13%, p< 0.0001). Otherwise patients were comparable (Table 1).Table 1.Comparison of TOC patients and matched controls.TocilizumabN=152Matched controlsN=152pGender female, n (%)128 (84)124 (81)0.65Disease duration, mean (SD), years5.4 (4.1)3.0 (2.9)<0.0001RF neg. polyarthritis, n (%)104 (68.4)92 (60.5)0.19RF pos. polyarthritis, n (%)14 (9.2)19 (12.5)0.46Extended oligoarthritis, n (%)34 (22.4)41 (27)0.42Pretreatment with biologics, n(%)127 (83.5)20 (13.2)<0.0001Active joint count, mean (SD)6.7 (7.1)6.1 (5.1)0.4CHAQ DI, mean (SD)0.63 (0.63)0.65 (0.64)0.8ESR, mm/h, mean (SD)17.5 (14.9)20.9 (20.6)0.1JADAS10, mean (SD)16.8 (9.8)15.1 (5.8)0.067Efficacy Month 12N=87N=105JADAS MDA, n (%)50 (57.5)63 (60.0)0.77JADAS REM, n (%)32 (36.8)39 (37.1)1.0JIA ACR 30/50/70/90, %80/75/61/5386/84/70/560.34/0.15/0.17/0.66Adverse eventsN (rate/100PY; 95%CI)248,65 PY290.4 PYRR (95%CI); pAE145 (58.3; 50-69)157 (54.1; 46-63)1.1 (0.9-1.4); 0.5SAE12 (4.8; 2.7-8.5)4 (1.4; 0.5-3.7)3.5 (1.1-10.9); 0.03Medically important infection2 (0.8; 0.2-3.2)12 (4.1; 2.3-7.3)0.2 (0.04-0.9); 0.03Uveitis event2 (0.8; 0.2-3.2)12 (4.1; 2.3-7.3)0.2 (0.04-0.9); 0.03Upon TOC a substantial response to treatment with a significant reduction in JADAS 10 from 16.8 to 3.4 (p<0.0001) after 12 months was observed. There were no significant differences between patients from the TOC cohort and their matched controls regarding JIA ACR 30/50/70/90 criteria and active joint counts. JADAS 10, JADAS remission (REM) and minimal disease activity (MDA) was reached by comparable numbers in the TOC (37% and 58%) and the control cohort (37% and 60%).While the total number of AE was comparable between the TOC cohort (58/100PY) and in the control cohort (54/100PY; RR 1.1; 95%CI 0.9-1.4), more serious AE (SAE) were reported with TOC (4.8/100PY compared to 1.4/100PY; RR 3.5; 95% CI 1-10.9). Medically important infections and uveitis events were documented at significantly lower frequency in the TOC- (0.8/100PY) than in the control cohort (4.1/100PY; RR 0.2; 95% CI 0.04-0.9). SAE with TOC were suicidal intent (n=3), depression (n=2), exacerbation of JIA, abscess, gastrointestinal infection, abdominal pain, colitis, bone surgery and fracture (n=1). SAE in the control cohort were depression, osteomyelitis, gastrointestinal infection and superinfected eczema (n=1). No significant differences regarding cytopenia and elevated transaminases were observed. No gastrointestinal perforation, no vascular event, no malignancy and no death occurred.Conclusion:The efficacy of tocilizumab is comparable to that of alternative biologics. Tolerability was acceptable. As Tocilizumab was given as a second-line biologic in the vast majority of patients, comparisons between the cohorts have to be interpreted carefully. Observation in the registry is ongoing.Disclosure of Interests:Ariane Klein Consultant of: Celgene, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Sandra Hansmann Consultant of: Advisory board Novartis Pharma, Jasmin Kuemmerle-Deschner Grant/research support from: Novartis, Sobi, Consultant of: Novartis, Sobi, Speakers bureau: Novartis, Sobi, Maria Fasshauer Consultant of: Shire, CSL Behring, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Ivan Foeldvari Consultant of: Novartis, Christoph Rietschel Consultant of: Pfizer, Abbvie, Novartis, Chugai, and Sobi, Tobias Schwarz: None declared, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell Grant/research support from: Novartis, Sobi, Pfizer, Speakers bureau: Novartis, Sobi, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prasad Oommen Consultant of: Novartis, Frank Dressler: None declared, Astrid Helling-Bakki: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche