Objective To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). Methods A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model’s parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. Results In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. Conclusions Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€− 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points• Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime.• Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs.• In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.
Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6-24month duration and long-term extension studies with [ 7061 patients and 22,875 patientyears of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the longterm safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.
Introduction There is few data about long-term outcomes of conservative management (without catheter ablation) of patients with a first episode of arrhythmic storm (AS) in the current context. This study analyzes the short and long-term outcomes of implantable cardioverter defibrillator (ICD) patients with a first episode of AS receiving non-interventional management. Methods Consecutive patients admitted with a first episode of AS between January 2008 and June 2019 receiving medical management without catheter ablation were included. AS was defined as 3 or more appropriate ICD therapies occurring during a 24 h span. Medical management included: correction of triggers, sedation/mechanical ventilation, antiarrhythmic drugs, ICD reprogramming and neuraxial modulation. Baseline clinical characteristics and follow-up data were recorded. All patients were followed every 6 months at the ICD office. The primary end-point was all-cause mortality. Results 60 patients (81% male, 62.8±16.2 years, 43% ischaemic, LVEF 35.4±14%) with a first episode of AS treated conservatively were included. Thirty-day survival was 96.5% and 1-year survival was 82%. During a median (interquartilic range) follow-up of 31 (6–69) months, 31 (51.7%) patients died (51.6% due to cardiovascular aetiology) and 35 (58.3%) patients were readmitted (48.5% due to recurrent arrhythmic events and 45.7% due to heart failure). Age [HR 1.05 (95% confidence interval: 1.01–1.08)] and end-diastolic diameter [HR 1.05 (95% confidence interval: 1–2)] were the strongest independent predictors of all-cause mortality. Conclusion Despite the severity of this entity, medical management (without catheter ablation) of a first episode of AS is reasonable given its good 30-day and 1-year survival. However, a high rate of AS recurrence and readmissions are observed during long-term follow-up. Efforts are needed in order to identify those patients with a first episode of AS that could benefit from an early catheter ablation strategy. Funding Acknowledgement Type of funding source: None
Background:The availability of oral janus kinase inhibitors, as tofacitinib, has extended the treatment pathways for management of patients with rheumatoid arthritis (RA)Objectives:To assess the cost-effectiveness of tofacitinib as second-line treatment compared to treatment sequences containing standard biological-therapies in patients with moderate to severe RA after failure to disease-modifying antirheumatic drugs (DMARDs) from the Spanish National Health System perspective.Methods:A patient-level microsimulation model was used to compare the lifetime cost and quality-adjusted life-years (QALY) for treatment sequences initiating with tofacitinib (5mg BID) followed by biological therapies versus sequences of biological treatments excluding tofacitinib. The sequences were selected by a panel of experts based on clinical practice in Spain. Concomitant treatment with methotrexate (MTX) was considered along all the therapies in the treatment sequences.Model parameters included age, weight, initial Health Assessment Questionnaire (HAQ) score and clinical response to short and long treatment. Efficacy was measured by means of HAQ score changes using mixed-treatment-comparisons (for the first 6 months) and data from long-term extension trials (for later periods).Serious adverse event (SAE) information derived from literature.The estimation of total cost for sequences included: drugs acquisition (public ex-factory prices with mandatory deduction or reference prices) and parenteral administration, disease progression and SAE management. Local unitary costs (€, 2018) were applied. Additional comparisons were explored testing other potential sequences.Results:The base case results showed that sequences initiating with tofacitinib provided greater outcomes than the correspondent sequences excluding tofacitinib. In scenario 1 tofacitinib+MTX→Rituximab+MTX→sc Tocilizumab+MTX→Etanercept+MTX→Certolizumab+MTX provided 13.99 QALYs versus 13.92 QALYs for adalimumab+MTX→Rituximab+MTX→sc Tocilizumab+MTX→Etanercept+MTX→Certolizumab+MTX. In scenario 2 tofacitinib+MTX→Adalimumab+MTX→Rituximab+MTX→sc Tocilizumab+MTX→Etanercept+MTX provided 13.75 QALYs versus 13.62 QALYs for Baricitinib+MTX→Adalimumab+MTX→Rituximab+MTX→sc Tocilizumab+MTX→Etanercept+MTX.Tofacitinib-containing sequences provided lower total costs than the alternative sequences (-€5,783 and -€13,975 for the pairwise comparisons previously described), resulting, therefore, dominant options versus sequences excluding tofacitinib.On the probabilistic sensitivity analyses, sequences initiating with tofacitinib resulted cost-effective in 64.0% (scenario 1) and 56.9% (scenario 2) of the 1,000 iterations performed, because incremental cost-effectiveness ratio fell below a €25,000/QALY gained willingness to pay threshold.Conclusion:These results suggest that the inclusion of tofacitinib could be a dominant strategy for treatment of moderate to severe RA patients after DMARDs failure in Spain.Disclosure of Interests:Carmen Peral Shareholder of: Carmen Peral is employee of and shareh...
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