Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform ...a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque psoriasis.
A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interest were SEC, ADA, INF, and placebo (PLA), while outcomes of interest were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI responses in different categories of PASI thresholds within a single model.
A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better response compared with PLA and ADA for PASI 75 and 90, while response results were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SEC vs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), respectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and 90.
Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA.
The objective was to systematically review the literature and assess the relative efficacy of agents approved in first-line settings via network meta-analysis.
A literature review was conducted via ...searching different medical databases. The eligibility criteria included Phase II or III randomized controlled trials that had enrolled treatment-naive adult patients with advanced/metastatic melanoma.
The network meta-analysis results suggested that dabrafenib + trametinib significantly prolongs the survival outcomes compared with the monotherapies and had comparable efficacy profile compared with encorafenib + binimetinib and cobimetinib + vemurafenib. In comparison with immunotherapies, the results varied for progression-free survival and overall survival.
Long-term survival data of dabrafenib + trametinib establishes the combination as one of the preferred treatment options for previously untreated melanoma patients.
To assess the cost-effectiveness of pazopanib versus sunitinib as a first-line treatment for patients with metastatic renal cell carcinoma (mRCC) from an Italian National Health Service perspective, ...considering the evolving Italian landscape in terms of new reimbursement agreements trend.
This analysis is an update of the previously published cost-effectiveness analysis to incorporate recent 2019 costs and additional changes regarding drug discounting. A partitioned-survival analysis model with three different health states (progression-free survival, post-progression survival, and dead) was utilized. Outcomes included progression-free life years, post-progression life years, overall life years, quality-adjusted life years (QALYs), and costs calculated for both treatments. Cost-effectiveness was assessed in terms of incremental costs per QALY gained and the net monetary benefit (NMB) of pazopanib versus sunitinib. In the base case analysis, a time horizon of 5 years was used and future costs and QALYs were discounted at a 3% annual discount rate. An impact of methodological and parameter uncertainly on base case results was evaluated using probabilistic and deterministic sensitivity analyses.
In the base case, pazopanib had higher QALYs (+0.060) at lower costs (-€5,857) versus sunitinib, hence it dominated sunitinib. At willingness-to-pay thresholds of €30,000 and €50,000 per QALY, the NMB with pazopanib were €7,647 and €8,841 per patient, respectively, versus sunitinib. The probability that pazopanib is cost-effective versus sunitinib was estimated to be 97.5% at a cost-effectiveness threshold of €20,000, 95.4% at a threshold of €30,000, and 90.2% at a threshold of €50,000 per QALY. Cost-effectiveness results were robust to changes in key parameter values and assumptions as demonstrated by deterministic sensitivity analyses.
Pazopanib is likely to represent a cost-effective treatment option compared with sunitinib as a first-line treatment for patients with metastatic RCC in Italy.
Introduction
Chronic spontaneous (previously known as idiopathic) urticaria (CSU) is a chronic skin disease with the potential for natural remission. The objectives of this targeted literature review ...were to identify evidence on the clinical course of CSU, including remission rates, and to estimate cumulative remission rates for different time points.
Methods
Electronic databases (MEDLINE, MEDLINE-In Process, Embase, Web of Science, BIOSIS Previews and the Cochrane Library) and relevant conference proceedings were searched to identify studies involving patients with CSU aged ≥ 12 years that provide data on remission rates and disease duration. Observational studies with patient follow-ups of ≥ 1 year or review articles were included. Data extracted from five selected studies were used to run Kaplan–Meier (KM) analyses and best-fit distributions to calculate remission rates per 4-week period and weighted averages.
Results
Ten publications were included in this review. The proportion of patients achieving remission within year 1 ranged from 21 to 47%, while reported remission rate estimates at year 5 were 34% and 45%. Based on calculated 4-weekly remission rates, cumulative remission estimates ranged from 9 to 38% at year 1, from 29 to 71% at year 5 and from 52 to 93% at year 20. Cumulative weighted average estimates for the proportion of patients remitting at years 1, 5 and 20 were 17%, 45% and 73%, respectively.
Conclusions
Published evidence suggests that CSU is a self-limiting condition with variable disease severity and duration, apparently dependent on multiple factors. However, data sources differed in terms of definitions of disease severity and remission, as well as in conclusions on influencing factors. Further studies and uniform definitions are required.
BackgroundAdoptive cell therapy demonstrated significant clinical benefit in patients with hematological malignancies but results in most solid tumors have been less encouraging so far.In the IMA203 ...trial we are treating advanced solid cancer patients utilizing TCR-engineered T cells (TCR-T) directed against an HLA-A*02-restricted peptide derived from the highly prevalent cancer testis antigen PRAME. This target was selected due to homogenous expression and exceptionally high target peptide density per tumor cell (assessed by quantitative mass spectrometry), two features we hypothesize to be critical determinants of anti-tumor activity in TCR-T trials.MethodsThis ongoing first-in-human, dose escalation, multi-indication trial enrolls HLA-A*02:01- and PRAME-positive recurrent and/or refractory solid cancer patients, who failed all available standard treatments. Eligible patients undergo leukapheresis and an autologous TCR-T product is manufactured. After lymphodepletion with fludarabine and cyclophosphamide, T cells are infused, followed by low-dose IL-2. The primary objective of the trial is to assess the safety and tolerability of IMA203. Secondary objectives are to evaluate the anti-tumor activity and pharmacodynamics using molecular and immunological methods.ResultsAs of August 15, 2021, 16 heavily pre-treated patients received IMA203 T cells across multiple escalating dose levels (DL). Absolute IMA203 doses infused ranged from 0.08 to 0.81x109 transduced CD8 T cells per patient, which to our knowledge did not lead to anti-tumor responses in other TCR-T trials. Treatment-emergent adverse events after IMA203 infusion were transient and manageable. Most common events were expected cytopenias (G1-4), CRS and ICANS (both G1-2) and 1 DLT in DL2 (reported earlier). All evaluable patients (N=12) achieved disease control (i.e. best overall response: stable disease SD or partial response PR) and 6 patients demonstrated PRs according to RECIST1.1 with 2 of these PRs being confirmed. While all 3 patients treated at DL1 (median dose: 0.11x109) experienced SD, a PR was observed in 6/9 patients treated beyond DL1 (median dose: 0.30x109). Responses were seen in patients with synovial sarcoma (N=3), malignant melanoma (N=2) and head and neck cancer (N=1). Robust engraftment of T cells was observed in all patients and tumor infiltration by TCR-modified T cells was demonstrated in patients with evaluable on-treatment biopsies.ConclusionsTo our knowledge IMA203 is the first TCR-T product candidate that induced frequent tumor responses across multiple solid cancers using transduced T cells at doses below 1 billion and has a manageable safety profile. The next step is to assess response rates at higher dose levels and durability of responses.Trial RegistrationNCT03686124Ethics ApprovalThe study was approved by the institutional review board/ethics committee as required for each participating site.
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