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

ABSTRACT: Objective:The 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. Methods:In 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. Results:Of 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. Conclusion:TCZ-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 registration:ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02046603.

SUBMITTER: Isaacs JD

PROVIDER: S-EPMC6649953 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Isaacs John D JD Salih Abdelrazig A Sheeran Thomas T Patel Yusuf I YI Douglas Karen K McKay Neil D ND Naisbett-Groet Barbara B Choy Ernest E

Rheumatology advances in practice 20190419 1

<h4>Objective</h4>The 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.<h4>Methods</h4>In 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 a ...[more]

PMID: 31431998

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Project description:BackgroundThe treatment of rheumatoid arthritis is based on the use of disease-modifying antirheumatic drugs (DMARDs). Tocilizumab can be used as monotherapy or in combination with conventional synthetic DMARDs for the treatment of moderate-to-severe active rheumatoid arthritis. Subcutaneous (SC) and intravenous forms of the drug are available, but the SC form is more widely used.ObjectiveTo understand the real-world dose modification patterns of SC tocilizumab in the treatment of patients with rheumatoid arthritis in the United States.MethodsData were obtained from the Truven (now IBM) MarketScan and Optum Clinformatics databases. Patients were included if they had ≥1 pharmacy claims for SC tocilizumab and met other inclusion criteria. The mean, standard deviation, and median values were reported for the continuous variables, and frequency was reported for the categorical variables. Kaplan-Meier analysis was used to analyze the time to first dose modification. Logistic regression modeling was used to identify predictors of the likelihood of dose modification.ResultsThe study included 1266 patients in the Truven database and 512 patients in the Optum database who had commercial or Medicare Advantage or supplemental insurance. Of the patients who started treatment with biweekly SC tocilizumab (48% each in the Truven and Optum databases), 37% in Truven and 40% in Optum had dose escalation to a weekly dose. Of those who started weekly SC tocilizumab (43% in the Truven and 49% in the Optum databases), 3% (Truven) and 4% (Optum) had dose reduction. The remaining patients started alternative SC tocilizumab doses. Overall, 60% and 68% of patients in the Truven and Optum cohorts, respectively, initiated or escalated to the higher weekly dose of tocilizumab; the mean time to dose escalation was 126 days and 112 days, respectively. In the Truven cohort, corticosteroid use, age, and anemia were the main predictors for dose escalation. In the Optum cohort, female patients had increased odds of dose escalation compared with male patients.ConclusionThe dosing trends observed in this study show that physicians have taken advantage of the option to increase SC tocilizumab dosing, but only a few providers chose to reduce the dose. This trend in dose modification may increase the costs related to SC tocilizumab therapy.

Project description:Rheumatoid arthritis (RA) is a chronic systemic autoimmune condition which affects approximately 1% of the adult population worldwide and is characterized by joint inflammation, with extra-articular features being common. Interleukin 6 (IL-6) is one of the chief pro-inflammatory cytokines found in the joints and sera of patients with RA. Increased levels of IL-6 correlate with inflammation, disease activity, and radiological damage. RA treatment should focus on minimizing the signs and symptoms of disease (pain, stiffness, and swelling of the joints) and on preventing or minimizing joint damage to preserve functionality and quality of life. The benefits of early, intensive intervention are now acknowledged, with all patients with newly diagnosed, active RA being started on methotrexate (MTX) monotherapy or combination therapy. Lack of efficacy, intolerance, and/or toxicity can lead to discontinuation of this drug, and there is a need for exploring further treatment options. In the UK, patients with persistently high disease activity who have failed at least two conventional disease-modifying agents (DMARDs) including MTX may qualify for biologic therapy. Numerous trials have shown intravenous (IV) tocilizumab (TCZ), a biologic drug targeting and inhibiting IL-6, to be effective for controlling inflammation in RA, with an acceptable safety profile. Its superiority in monotherapy when compared with other biologic agents makes it the drug of choice for patients who are intolerant or have contraindications to traditional DMARDs. However, one of the drawbacks of IV TCZ is the requirement for monthly infusions, which is inherently inconvenient for the patient and associated with increased cost. Subcutaneous (SC) TCZ has now been approved following two clinical trials which showed similar efficacy and safety compared to IV TCZ, and better efficacy compared to placebo (SUMMACTA and BREVACTA trials, respectively). Respiratory infections are the most common side effects in patients receiving SC TCZ. Advantages of SC formulations include convenience and reduced cost compared with IV therapies. Overall, patients tend to have a preference for SC over IV administration of medications. Close monitoring of patients should be undertaken in all cases, paying particular attention to the full blood count, liver enzymes, and cholesterol levels.

Project description:IntroductionControlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.MethodsTCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap).ResultsPatients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups.ConclusionsIn this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity.FundingCorrona, LLC. Plain language summary available for this article.

Project description:IntroductionThis study was conducted to observe patterns of use of the interleukin-6 receptor-alpha inhibitor tocilizumab in routine clinical practice in patients with rheumatoid arthritis (RA).MethodsThis was a 12-month noninterventional, observational study in adult patients with RA who initiated tocilizumab in routine practice in Canada according to the local product monograph. The primary end point was the proportion of patients receiving tocilizumab at 6 months. Secondary end points were treatment patterns, effectiveness, and safety of tocilizumab over 12 months.ResultsOf 200 patients who initiated tocilizumab (91.0% at 8 mg/kg), 67 (33.5%) received tocilizumab monotherapy and 133 (66.5%) received tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Kaplan-Meier analysis estimated that 85% (95% CI 74-92%) of monotherapy and 89% (95% CI 82-93%) of combination therapy patients continued to receive tocilizumab at 6 months (log-rank p = 0.0888). During the observation period, 12 (17.9%) monotherapy and 27 (20.3%) combination therapy patients withdrew from the study. At month 12, 58.5% in the monotherapy group and 59.3% in the combination therapy group achieved Disease Activity Score at 28 joints remission (≤ 2.6), 25.6% and 24.7% achieved Simplified Disease Activity Index remission (≤ 3.3), and 18.2% and 22.3% achieved Clinical Disease Activity Index remission (≤ 2.8), respectively. Rates of serious adverse events and serious infections were found in 29.6/100 patient-years (PY) and 3.1/100 PY, respectively, for monotherapy and 19.2/100 PY and 4.8/100 PY, respectively, for combination therapy.ConclusionsPatients initiating tocilizumab in routine practice had comparable effectiveness and safety outcomes regardless of whether they received tocilizumab as monotherapy or as combination therapy with csDMARDs.Trial registrationClinicalTrials.gov identifier, NCT01613378 FUNDING: F. Hoffmann-La Roche (Roche) Canada.

Dataset Information

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

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

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