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Background/Purpose: Tocilizumab (TCZ) treatment has been associated with reduced neutrophil counts in adults with rheumatoid arthritis and in children with systemic juvenile idiopathic arthritis. The aims of this study were to assess changes in neutrophil counts, determine whether neutropenia was associated with increased risk for infection, and investigate variables associated with the development of neutropenia in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) receiving TCZ for up to 2 years in the CHERISH trial. Methods: One hundred eighty-eight patients (2-17 years) with active pcJIA and inadequate response to methotrexate received open-label (OL) TCZ according to body weight (BW) (BW ≥30 kg, TCZ 8 mg/kg; BW <30 kg, randomly assigned 1:1 to TCZ 8 or 10 mg/kg) every 4 weeks for 16 weeks. Patients who achieved ≥JIA ACR30 response at 16 weeks entered a 24-week, randomized, double-blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. Patients who experienced JIA ACR flare or who completed the withdrawal period entered an OL extension through week 104. Blood cell counts were monitored every 4 weeks. Worst Common Toxicity Criteria (CTC) neutrophil grade and lowest observed neutrophil count (109/L) were identified for each patient. Rates of infection and serious infection (per 100 patient-years [PY]) in periods ±30 days around grade 1/2 and around grade 3/4 neutrophil counts were compared with corresponding rates in periods with normal neutrophil counts. Univariate linear regression analysis was used in patients enrolled in part 3 of the study to investigate the association between patient baseline characteristics and lowest observed neutrophil count from baseline to week 104. Results: At baseline, all patients had neutrophil counts within or above the normal range. Median neutrophil count decreased during the first 16 weeks of treatment and stabilized for the remainder of the study. Throughout the 2-year study, 118 patients (62.8%) had normal neutrophil counts, whereas CTC grades 1, 2, 3, and 4 neutrophil counts were reported in 15 (8.0%), 44 (23.4%), 11 (5.9%), and 0 (0.0%) patients, respectively. Infections and serious infections occurred at rates of 151.4/100 PY and 5.2/100 PY, respectively. All serious infection events (n = 16) occurred during periods of normal neutrophil count. Rates of infection during periods of normal, grade 1/2, and grade 3 neutrophil count were 147.8/100 PY (95% CI, 133.9-162.7), 176.6/100 PY (95% CI, 128.8-236.3), and 340/100 PY (95% CI, 136.7-700.5), respectively, with largely overlapping confidence intervals. Low neutrophil count was not associated with any baseline covariates investigated. Conclusion: In the CHERISH trial, there was no evidence of increased rates of serious infection associated with low neutrophil count. The prevalence of neutropenia in the pcJIA population was lower than in other disease groups (eg, systemic JIA) treated with TCZ. [ABSTRACT FROM AUTHOR]

Background/Purpose: Treatment with anti-TNF therapies (anti-TNF) for polyarticular forms (extended oligo, Poly RF +/−) of JIA (PF-JIA) results in >50% demonstrating clinically inactive disease (CID). The aims of this study were to determine the frequency, timing and predictors of flare upon withdrawal of anti-TNF in PF-JIA in CID. Methods: In 16 centers 137 children with PF-JIA in CID on anti-TNF were enrolled and followed for ≥14 mos. If CID was maintained for the first 6 study mos, then anti-TNF was stopped. The primary outcome variable was a validated definition of disease flare within 8 months after stopping anti-TNF. Background meds were stable. Blood for S100, DEK, DNA and RNA was drawn for current and future biomarker and genetic studies. Results: The study population included 18 (13%) extended oligarticular, 17 (12%) RF+ Poly and 102 (74%) RF- Poly JIA patients. At enrollment, age (mean/median/range) was 11.3/11.6/3.4-20.1 yrs; disease duration was 5.0/4.1/0.6-18.6 years; 103 (75%) were females and 64 (47%) were ANA+. Duration of CID at baseline was 1.2/0.5/1 day-12.1 yrs. Anti-TNF was etanercept in 106 (77%), 25 (18%) adalimumab and 6 (5%) infliximab. 40% were on MTX at baseline (mean/median dose 0.4/0.4 mg/kg/week). Other meds: 1 leflunomide, 2 hydroxychloroquine, and 1 prednisolone. 31 (23%) subjects were discontinued from the study in the first 6 mos: 23 (17%) due to loss of CID, 5 (4%) med noncompliance, 2 (1%) moved/LTF, 1 (1%) ILAR subtype changed (oligo to psoriatic). For the extended oligo, Poly RF− and Poly RF+ categories 94%, 82% and 60%, respectively, maintained CID for the first 6 months (c2 6.7, p 0.03). ANA status, MTX use, and type of anti-TNF were not associated with the ability to maintain CID (c2 p values 0.48, 0.14, and 0.75, respectively). 106 (77%) subjects maintained CID for the first 6 months and stopped anti-TNF as per protocol. 67/106 (63%) maintained CID for ≥8 mos off anti-TNF while 39 (37%) flared. Time without flaring after stopping anti-TNF therapy was duration from the month 6 visit to the last study visit (mean/median/range for duration of followup was 249/250/126-322 days). The mean/median/range for time to flare was 108/105/7-271 days. Time to flare (days) for etanercept was 105/105/7-271, adalimumab 119/120/28-238 and infliximab 28/28/28. Flare was seen in 47% (8/17) extended oligo, 37% (30/80) poly RF- and 11% (1/9) poly RF+ ((c2 p-value 0.19). In those on background MTX, 33% (13/40) flared at a mean of 90 days, while those not on background MTX, 39% (26/66) flared at a mean of 113 days ((c2 p-value 0.48). Using univariate analysis of variance, only weak correlations of MTX dose, disease duration, and CID duration with flare/no flare were seen (Spearman correlations −0.03, −0.17, −0.19, respectively). Conclusion: In this prospective multicenter study, 77% of the PF-JIA patients were able to maintain CID for the first 6 months on anti-TNF. Discontinuation of anti-TNF in PR-JIA (who have demonstrated on average 1.8 years of CID) resulted in a flare rate of 37% within 8 mos. Clinical parameters had only minimal predictive ability. Ongoing work includes biomarker identification and continued follow-up of the cohort. [ABSTRACT FROM AUTHOR]