Dataset Information

Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

ABSTRACT:

Objective

To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA).

Methods

Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE.

Results

Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection).

Conclusion

Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile.

Clinical trial registration

clinicaltrials.gov, NCT02165345.

SUBMITTER: Brunner HI

PROVIDER: S-EPMC11371380 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Publications

Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

Brunner Hermine I HI Ruperto Nicolino N Ramanan Athimalaipet V AV Horneff Gerd G Minden Kirsten K Calvo Penades Inmaculada I Alexeeva Ekaterina E Cleary Gavin G Stern Sara M SM Kone-Paut Isabelle I Maldonado Velázquez María Del Rocío MDR Rabinovich C Egla CE Remesal Agustin A Silva Clovis Artur CA Nikishina Irina I Zucchetto Mauro M Brockwell Laura L Gordon Oliver O Nagel Sandra S De Benedetti Fabrizio F

Rheumatology (Oxford, England) 20240901 9

<h4>Objective</h4>To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA).<h4>Methods</h4>Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial avai ...[more]

PMID: 38552315

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Project description:BackgroundFew clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti-interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively.MethodsStandard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp-van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference.ResultsPoznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were - 2.4 and 24.6 for sJIA patients and - 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring.ConclusionTocilizumab may delay radiographic progression in children with sJIA and children with pcJIA.Trial registrationTrial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009).

Project description:ObjectiveTo report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA).MethodsPatients 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.ResultsOverall, 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.ConclusionPatients 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.

Dataset Information

Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

Objective

Methods

Results

Conclusion

Clinical trial registration

Publications

Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

Similar Datasets

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