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Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

ABSTRACT: Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody, a novel therapy for rheumatoid arthritis (RA) patients who fail treatment with disease modifying anti-rheumatic drugs (DMARDs) or anti-tumor necrosis factor (anti-TNFs).To assess the safety and efficacy of TCZ monotherapy or in combination with non-biologic DMARDs or anti-TNFs in moderate to severe active RA.Prospective, phase III, multi-center, open-label, single arm, 24-week trial.Three centers in Saudi Arabia.The study included consecutive RA patients infused with TCZ (8 mg/kg) over 60 minutes every 4 weeks (up to 6 times), either alone or with non-biologic DMARDs. Patients were followed for 24 weeks. Patients with good/moderate European League Against Rheumatism responses, continued on TCZ as long as commerically available or for 1 year.Disease activity measured by DAS28 score.Of 28 patients enrolled from 2 November 2011 to 12 May 2013 (18 months), 21 completed (77.8%) and 7 (25%) discontinued TCZ therapy. One patient was excluded from the intent-to-treat analysis. Efficacy analysis showed a significant difference (P < .0001) in the Disease Activity Score based on 28 joints and on swollen and tender joint counts. Three (10.7%) patients experienced at least one AE that was considered related to study drug (one probably and two possibly). Only one (3.6%) patient reported a severe adverse event (neutropenia and thrombocytopenia). No adverse events led to dose modification or death.TCZ monotherapy or in combination with non-biologic DMARDs resulted in a significant effect on the endpoints in moderate to severe RA in Saudi Arabia, which is consistent with other published reports.No information on tapering of steroid therapy, lack of follow-up data of all 28 patients, lack of data on long-term effects of TCZ on lipid levels and the need for statins. (ClinicalTrials.gov identifier: NCT01326962).

SUBMITTER: Abdulkader OAF

PROVIDER: S-EPMC6074539 | biostudies-literature | 2016 May-Jun

REPOSITORIES: biostudies-literature

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Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

Abdulkader Omer Ahmad Fatheddin OAF Qushmaq Khalid K Aljishi Faiza F

Annals of Saudi medicine 20160501 3

<h4>Background</h4>Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody, a novel therapy for rheumatoid arthritis (RA) patients who fail treatment with disease modifying anti-rheumatic drugs (DMARDs) or anti-tumor necrosis factor (anti-TNFs).<h4>Objective</h4>To assess the safety and efficacy of TCZ monotherapy or in combination with non-biologic DMARDs or anti-TNFs in moderate to severe active RA.<h4>Design</h4>Prospective, phase III, multi-center, open-label, single arm, 24-week trial.<h ...[more]

PMID: 27236390

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Project description:BackgroundKnowledge of factors that contribute to non-persistence with disease modifying anti-rheumatic drugs (NP) is essential to improve rheumatoid arthritis (RA) outcomes. Aims of the study were to investigate patient's motivations and risk factors for NP in a cohort of early RA patients.MethodsUp to September 2012, data from 149 patients, who had at least 1 year of follow-up, at least one drug indication, and at least 2 consecutive six-months-apart rheumatic evaluations that included assessment of compliance were reviewed. NP and patient's motivations of NP were evaluated according to a questionnaire. NP was defined when patients referred that they had completely stop RA medication, "Sometimes", "Almost always" or "Always". Patients had to pay for their medication.Descriptive statistics and logistic regression models were used. Statistical significance was set at a p value of less than 0.05. The study was approved by the internal review board.ResultsUp to cut-off, 715 questionnaires were applied to 149 patients, who had follow-up of 58.7?±?27.9 months and were indicated 2.4?±?0.7 DMARDs/patient/follow-up.Patients were most frequently female (88.6%), middle-aged ([mean?±?SD] age of 38.5?±?12.8 years) with lower-middle/lower socio-economic status (87.9%) and scholarship of 11?±?3.9 years.Ninety-nine (66.4%) patients were NP and filled 330 questionnaires. Multivariate analysis showed that years of formal education (OR: 1.12, 95% CI: 1.1-1.24, p?=?0.03), perception of at least some difficulty to find arthritis medication (OR: 5.68, 95% CI: 2.48-13, p?=?0.000) and perception that arthritis medication is expensive (OR: 5.27, 95% CI: 2.1-13.84, p?=?0.001) at the first evaluation of patient's compliance were all predictors of NP.Among the 99 NP patients, 25 (25.3%) were recurrent-NP and accumulated more disease activity. The combination of both reasons of NP ("Because it was not available at the drugstore" and "Because the medication is very expensive") when selected at the first evaluation of compliance was the only variable to predict recurrent NP, OR: 4.8, 95% CI: 1.1-20.8, p?=?0.04.ConclusionsHealth systems should provide (first line) treatment for RA as a strategy to improve compliance with therapy and clinical outcomes, particularly in vulnerable populations.

Project description:ObjectiveTo evaluate the efficacy and safety of sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with active moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapy.MethodsPatients were randomly allocated to receive sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks for 24 weeks with background conventional synthetic DMARDs. The co-primary end points were the proportion of patients achieving a response according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 24, and change from baseline in the Health Assessment Questionnaire disability index (HAQ DI) at week 12. Each sarilumab dose was evaluated against placebo; differences between the 2 sarilumab doses were not assessed.ResultsThe baseline characteristics of the treatment groups were similar. The ACR20 response rate at week 24 was significantly higher with sarilumab 150 mg and sarilumab 200 mg every 2 weeks compared with placebo (55.8%, 60.9%, and 33.7%, respectively; P < 0.0001). The mean change from baseline in the HAQ DI score at week 12 was significantly greater for sarilumab (least squares mean change: for 150 mg, -0.46 [P = 0.0007]; for 200 mg, -0.47 [P = 0.0004]) versus placebo (-0.26). Infections were the most frequently reported treatment-emergent adverse events. Serious infections occurred in 1.1%, 0.6%, and 1.1% of patients receiving placebo, sarilumab 150 mg, and sarilumab 200 mg, respectively. Laboratory abnormalities included decreased absolute neutrophil count and increased transaminase levels in both sarilumab groups compared with placebo. In this study, reductions in the absolute neutrophil count were not associated with an increased incidence of infections or serious infections.ConclusionSarilumab 150 mg and sarilumab 200 mg every 2 weeks plus conventional synthetic DMARDs improved the signs and symptoms of RA and physical function in patients with an inadequate response or intolerance to anti-TNF agents. Safety data were consistent with interleukin-6 receptor blockade and the known safety profile of sarilumab.

Project description:ObjectiveTo determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs.DesignOpen label pragmatic randomised multicentre two arm non-inferiority trial over 12 months.Setting24 rheumatology clinics in England.ParticipantsPatients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy.InterventionsBiologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders.Main outcome measurePrimary outcomereduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy.Secondary outcomesquality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data.Results432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was -0.14, and the 95% confidence interval (-0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (€4930, $5585) for months 0-6 and £1930 for months 6-12.ConclusionsIn patients with active rheumatoid arthritis who meet English criteria for biologics an alternative strategy with combinations of intensive synthetic disease modifying drugs gives non-inferior outcomes to treatment with tumour necrosis factor inhibitors. Costs are reduced substantially.Trial Registration ISRCTN 37438295.

Dataset Information

Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

Publications

Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor.

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