Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic Arthritis: 2-year Data from a Phase III Clinical Trial

Bharucha, Kamal N.; Brunner, Hermine I.; Penadés, Inmaculada Calvo; Nikishina, Irina; Rubio-Pérez, Nadina; Oliveira, Sheila; Kobusińska, Katarzyna; Schmeling, Heinrike; Sztajnbok, Flávio; Weller‐Heinemann, Frank; Жолобова, Елена; Zulian, Francesco; Allen, Roger C.; Chaitow, Jeffrey; Frane, James W.; Wells, Chris; Ruperto, Nicolino; Benedetti, Fabrizio

doi:10.3899/jrheum.170326

Cited by 9 publications

(5 citation statements)

References 19 publications

(20 reference statements)

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“…Exploratory analysis of growth showed that the distribution of height velocities was consistent with World Health Organization normative values ( Supplementary Fig. S5 , available at Rheumatology online) and in line with observations for pJIA and sJIA with i.v.-TCZ [ 34 , 35 ].…”

Section: Resultssupporting

confidence: 83%

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

et al. 2021

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Objectives To determine subcutaneous-tocilizumab (SC-TCZ) dosing regimens for systemic juvenile idiopathic arthritis (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, SC-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or < 30 kg, respectively. Primary endpoints were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with intravenous-tocilizumab (IV-TCZ) in sJIA and pJIA. Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received SC-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with IV-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis Disease Activity Score-71 were comparable between SC-TCZ and IV-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of IV-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered related to TCZ. Conclusion SC-TCZ provides exposure and risk/benefit profiles similar to those of IV-TCZ. Subcutaneous administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, NCT01904292 and NCT01904279

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Section: Resultssupporting

confidence: 83%

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

et al. 2021

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“…TCZ therapy allowed for the discontinuation of steroids in 47% of these patients (31 of 66 patients) by week 104. As reported elsewhere (28), this reduction in glucocorticoid exposure, together with the degree of disease control achieved, is considered clinically relevant based on improved growth profiles. On average, mild-to-moderate disability (29) at baseline improved with TCZ treatment over a 2-year period.…”

mentioning

confidence: 82%

Efficacy and Safety of Tocilizumab for Polyarticular‐Course Juvenile Idiopathic Arthritis in the Open‐Label Two‐Year Extension of a Phase III Trial

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et al. 2021

Arthritis & Rheumatology

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Objective. To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods. Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure. Results. Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years. Conclusion. Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.

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“…In a small trial in 19 patients, 100% of patients met the criteria for a good response after 48 weeks of treatment with tocilizumab 95 . In a pivotal phase III trial and its subsequent long-term extension study in 188 patients, inhibition of IL-6 led to sustained and clinically meaningful improvements after 2 years, and skeletal growth was also improved by treatment with tocilizumab 96,97 . Another antibody to IL-6R, sarilumab, is in phase II trials for polyarticular JIA 98 and sJIA 99 .…”

Section: Il-6 Inhibition In Jia and Aosdmentioning

confidence: 99%

Translating IL-6 biology into effective treatments

et al. 2020

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Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic Arthritis: 2-year Data from a Phase III Clinical Trial

Abstract: Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.

Cited by 9 publications

References 19 publications

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

Efficacy and Safety of Tocilizumab for Polyarticular‐Course Juvenile Idiopathic Arthritis in the Open‐Label Two‐Year Extension of a Phase III Trial

Translating IL-6 biology into effective treatments

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