Safety Of Subcutaneous Tocilizumab Research Articles

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

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). 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. 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). 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. clinicaltrials.gov, NCT02165345.

Short-Term Efficacy and Safety of Subcutaneous Tocilizumab in Rheumatoid Arthritis Patients in Pakistan: A Real-World Experience

Objective: To determine the real-world efficacy and safety of subcutaneous Tocilizumab in patients with rheumatoid arthritis.&#x0D; Study Design: Case series.&#x0D; Place and Duration of Study: Department of Rheumatology, National Hospital and Medical Centre, Lahore Pakistan, from Aug 2019 to Dec 2020.&#x0D; Methodology: In this study, 33 patients receiving subcutaneous Tocilizumab 162 mg every two weeks as monotherapy or with conventional synthetic disease modifying anti-rheumatic drugs were followed per standard study protocol. Increasing or decreasing the dosing interval was allowed according to disease activity at the discretion of the treating rheumatologist. The primary outcome was patients achieving Low Disease Activity as per Clinical Disease Activity Index (&gt;2.8-10.0) and Disease Activity Score-28(&gt;2.6-3.2). The secondary outcome was a clinically meaningful improvement in Disease Activity Score -28 (reduction of ≥1.2 units in Disease Activity Score-28 score). Adverse events were recorded at each follow-up visit.&#x0D; Results: Of the 33 patients, 25(75.8%) were biologics-naive, 9(27.2%) patients achieved the target of Low Disease Activity as per Clinical Disease Activity Index (2.9-10.0) and 8(24.2%) patients achieved Low Disease Activity as per Disease Activity Score-28(2.7-3.2). At six months, the proportion of patients achieving clinically meaningful improvement (decrease ≥1.2) in Disease Activity Score -28 was 13(54.2%). Overall, 14(42.4%) patients developed adverse events and 3(9.1%) patients discontinued Tocilizumab owing to adverse events.&#x0D; Conclusion: Tocilizumab has been seen to be an effective biologic in only one-third of patients, and it was tolerated in twothirds of the patients.Keywords: Conventional synthetic disease modifying anti-rheumatic drugs, Efficacy, Rheumatoid arthritis, Safety, Subcutaneous tocilizumab.

Subcutaneous Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis

ABSTRACT Aim To describe the efficacy and safety of subcutaneous tocilizumab (SC-TCZ) in a cohort of juvenile idiopathic arthritis (JIA) patients with refractory uveitis. Methods Retrospective observational monocentric study including patients with JIA-associated uveitis treated with SC-TCZ. Results Thirteen patients were enrolled. The rate of uveitis flare/year per each patient was 1.6 ± 2.0 on the last bDMARDs before SC-TCZ, while it decreased to 0.4 ± 0.7 on SC-TCZ. Nine out of thirteen patients (69%) required the introduction of SC-TCZ only for active uveitis at baseline. Among these patients, five (56%) achieved complete treatment response. No uveitis relapses were observed in patients (4/13, 31%) requiring the introduction of SC-TCZ for active arthritis during follow-up (30.48 ± 21.6 months). Overall, SC-TCZ was safe, and no side effects were observed during the treatment. Conclusion SC-TCZ can be effective and safe in patients with JIA and uveitis recalcitrant to several bDMARDs.

Subcutaneous tocilizumab for active thyroid eye disease refractory to orbital radiation and systemic steroids in tobacco smokers.

PURPOSE:Tocilizumab (TCZ) through intravenous infusion has been shown to effectively treat active thyroid eye disease (TED) refractory to systemic steroids. TCZ is also available as a self-administered subcutaneous injection, but data demonstrating the efficacy of this formulation are limited. This study investigated the efficacy and safety of subcutaneous TCZ (SC-TCZ) for the treatment of active, moderate-to-severe TED in smokers.MATERIALS AND METHODS:This retrospective clinical case series evaluated the clinical outcomes and adverse effects of SC-TCZ when taken for a minimum of 4 months by patients with moderate-to-severe TED and a current or recent history of cigarette smoking.RESULTS:Three patients received SC-TCZ every 1-2 weeks (4.6-11.2 mg/kg/month). The average pre-to-posttreatment clinical activity score reduction was 5.4, and proptosis was reduced by an average of 2.0 mm. No serious adverse effects were reported.CONCLUSION:SC-TCZ may be a useful and effective therapy for treating challenging cases of inflammatory TED and offers a safe alternative to office or hospital-based infusions. Further studies are needed to better understand optimal dosing regimens and relative efficacy compared to monthly TCZ infusions and other immunotherapies.

Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis.

ObjectivesThis post hoc analysis of the TOZURA study programme evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or with concomitant conventional synthetic DMARDs (csDMARDs) in patients with RA categorized by baseline glucocorticoid (GC) use.MethodsTOZURA was a multinational, open-label, single-arm, common-framework study programme (11 protocols, 22 countries) in patients with moderate to severe RA in whom csDMARDs or biologic therapies had failed or who were MTX naïve. Patients received once-weekly TCZ-SC 162 mg for ⩾24 weeks as monotherapy or in combination with csDMARDs and/or oral GC use (⩽10 mg/day prednisone or equivalent), which was to be continued unchanged for 24 weeks. Treatment subgroups were defined by baseline GC use and analysed for efficacy and safety.ResultsOf 1804 patients who received TCZ-SC, 145 received monotherapy + GC, 208 received monotherapy without GC, 730 received combination therapy + GC and 721 received combination therapy without GC. The median GC dose in both GC subgroups was 5 mg/day. The proportion of patients who achieved clinical remission, defined as DAS in 28 joints using ESR <2.6, increased similarly from baseline to week 24 in all subgroups. Improvements in patient-reported outcomes were similar in all subgroups. Overall adverse event profiles were generally similar between subgroups, with some slight numerical differences between GC and non-GC subgroups.ConclusionThe incremental efficacy benefits of TCZ-SC as monotherapy and in combination with csDMARDs were similar between patients with and without previous and continued oral GC treatment, with generally similar safety profiles.Trial RegistrationClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603, NCT02046616.

Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study.

ObjectiveThe ACT-MOVE study assessed the real-world efficacy and safety of s.c. tocilizumab (TCZ-SC), provided as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 1 year, in patients with RA and an inadequate response to csDMARD therapy and/or first TNF inhibitor.MethodsIn this UK multicentre, open-label phase IIIb study, patients received TCZ-SC 162 mg once weekly for 52 weeks as monotherapy or with csDMARDs. Efficacy and safety were evaluated at baseline, weeks 2 and 4 and every 4 weeks thereafter up to week 52.ResultsOf 161 patients who received at least one dose of TCZ-SC, 21 (13.0%) received TCZ-SC alone and 140 (87.0%) TCZ-SC with a csDMARD(s). From baseline to week 52, there was a mean decrease in DAS28-ESR score among all patients (−3.68), and within monotherapy (−3.75) and combination therapy (−3.67) groups. The proportion of patients who achieved DAS28 clinical remission (DAS28-ESR <2.6) at week 52 was 75.4% (95% CI 66.8, 82.8). At the same time point, ≥80% of patients who remained on TCZ-SC achieved DAS28 clinical remission or had low disease activity (DAS28-ESR ≥2.6 and ≤3.2). Overall, 6.2% of patients had at least one serious adverse event (10.2/100 patient-years), and there was one death; 11.2% of patients discontinued owing to adverse events.ConclusionTCZ-SC was effective and tolerated in a real-world setting over 1 year. The efficacy of TCZ-SC was similar whether given as monotherapy or with csDMARDs; its safety profile was consistent with that previously established.Trial registrationClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02046603.

A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period

Objective: To determine the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) monotherapy every week (qw) versus every other week (q2w) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC q2w.Methods: Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162 mg qw monotherapy or TCZ-SC 162 mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed.Results: TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was −1.21 (95%CI: −2.13, −0.30, p = .0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw.Conclusions: In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.

058. The Efficacy and Safety of Subcutaneous Tocilizumab Versus Intravenous Tocilizumab in Combination with Traditional DMARDs in Patients with RA at Week 97: Results from the Summacta Study

058. The Efficacy and Safety of Subcutaneous Tocilizumab Versus Intravenous Tocilizumab in Combination with Traditional DMARDs in Patients with RA at Week 97: Results from the Summacta Study