ORCID Profile
0000-0002-7619-7167
Current Organisation
University of Manchester
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Publisher: Consilium Medicum
Date: 02-2023
DOI: 10.26442/18151434.2022.4.202034
Abstract: Aim. To assess the comparative clinical efficacy of Prolgolimab monotherapy versus combination therapy with BRAF/MEK inhibitors (Dabrafenib and Trametinib, Vemurafenib and Cobimetinb) in adult patients with metastatic or unresectable skin melanoma implementing a matching-adjusted indirect comparison (MAIC). Materials and methods. We conducted a systematic search for randomized clinical trials of Prolgolimab, combinations of Dabrafenib and Trametinib, Cobimetinib and Vemurafenib. Unanchored MAIC was applied due to the absence of common comparator between trials. We determined effect modifiers based on an expert survey. The population from Prolgolimab studies was weighted using defined effect modifiers, followed by the approximation of survival curves. Results. Systematic literature search revealed 4 RCTs that met the inclusion criteria: MIRACULUM, coBRIM, combi-v and combi-d. To increase the power of prolgolimab comparison, data from the observational study FORA were included in evidence synthesis and combined with data from MIRACULUM. We selected M staging and the proportion of patients with elevated LDH levels as effect modifiers. No significant differences (all p0.05) were established between Prolgolimab and combination therapy with BRAF/MEK inhibitors for both OS after 1 year and PFS outcomes after 2 years from initiation. Discussion. Despite the inclusion of observational data and the limitations of adjusted indirect comparison method, the results of this analyses are consistent with both other comparisons of anti-PD1 inhibitors with BRAF/MEK inhibitors, and with real world data. It is necessary to recompare targeted therapy and immunotherapy after five-year follow-up period due to peculiarities of time of onset of their effect with the presence of a primary failure with a gradual exit to a long plateau on anti-PD1 inhibitors therapy. Conclusion. In these unanchored MAICs, Prolgolimab monotherapy showed comparable efficacy with combinations of BRAF/MEK inhibitors (Dabrafenib + Trametinib, Vemurafenib + Cobimetinib) in first line therapy of patients with metastatic or unresectable melanoma. This analysis may be relevant for clinical decision-making about the choice of the first line therapy for patients with BRAF mutation.
Publisher: Mediar Press
Date: 14-01-2021
Publisher: IRBIS
Date: 27-07-2021
DOI: 10.17749/2070-4909/FARMAKOEKONOMIKA.2021.095
Abstract: Objective: to perform cost-effectiveness analysis of the treatment for adult patients with psoriatic arthritis (PsA) with a Russian interleukin- 17А inhibitor netakimab in comparison with other biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and to evaluate the influence of the inclusion of netakimab in the therapy for PsA on the budget of the Russian healthcare system. Material and methods. The evaluation of cost-effectiveness was performed from the position of the Russian healthcare system for patients with moderate and severe PsA. The evaluation was performed based on the results of the network meta-analysis of the randomized clinical studies. The criterion of clinical effectiveness included the changes in the condition of the joints by the criteria of the American College of Rheumatology (ACR20, ACR50, and ACR70) and changes in skin symptoms by the index of the prevalence and severity of psoriasis (PASI 75 and PASI 90) with a recalculation into quality-adjusted life-year (QALY). The time horizon of the cost-effectiveness analysis was 2 years. The calculation was based on the registered prices and VAT. If there was an original drug and a biosimilar registered on the pharmaceutical market, the calculation was based on the median of the registered prices. The budget impact analysis of the influence of netakimab inclusion in the therapy for patients with PsA was performed considering the structure of the prescription of bDMARDs and tsDMARDs that was determined in the pharmaco-epidemiological study conducted in the Russian Federation in 2020. The analysis was performed for patients that received medication by the scheme of reimbursement. The time horizon of the study was 3 years old. Results. In the base-case analysis, the cost-effectiveness ratio for netakimab was 1.210 mln rub/QALY (by 66.2–88.5% lower than in cases when comparison drugs were used). The budget impact analysis showed that the inclusion of netakimab in the therapy for PsA could reduce the costs by 376.60 mln rub (21.1%). Considering budget saving, the number of additional patients that can be treated will increase by 26.7% within 3 years. Conclusion. Netakimab is characterized by higher cost-effectiveness in comparison with other bDMARDs (adalimumab, golimumab, guselkumab, ixekizumab, infliximab, secukinumab, ustekinumab, certolizumab pegol, etanercept) and tsDMARDs (apremilast, tofacitinib) prescribed in the Russian Federation for patients with PsA. The inclusion of netakimab in the therapy for PsA will reduce the financial burden on the healthcare system.
Publisher: IRBIS
Date: 15-04-2022
DOI: 10.17749/2070-4909/FARMAKOEKONOMIKA.2022.128
Abstract: Background . A systematic literature review helps to identify the main treatment options, and evidence synthesis supports decision-making by comparing clinical efficacy of different treatments. Nowadays new drugs and clinical trials emerge rapidly, so previous network meta-analyses might need to be updated. Objective : to update the existing systematic review and network meta-analysis comparing efficacy of targeted drugs in adult patients with moderate-to-severe plaque psoriasis by adding randomized clinical trials (RCTs) on a new interleukin (IL) 23 inhibitor registered in the Russian Federation – risankizumab, and other RCTs published after 2019 to reassess the Psoriasis Area and Severity Index (PASI) 75/90 numbers of patients needed to treat to achieve clinical response to therapy and the costs per responder for 12–16 weeks and 1 year of therapy. Material and methods . We updated our systematic literature search in the PubMed/MEDLINE and Embase databases. Evidence synthesis included RCTs evaluating the efficacy of adalimumab (ADA), infliximab (INF), etanercept (ETN), certolizumab pegol (CZP), ixekizumab (IXE), netakimab (NTK), secukinumab (SEC), risankizumab (RIS), guselkumab (GUS), ustekinumab (UST), tofacitinib (TOFA), and apremilast (APR) after 12 weeks of therapy. The Bayesian meta-analyses with meta-regression models were performed in order to account for high heterogeneity in patient characteristics and significant differences in the placebo response rates. The considered drugs were ranked based on values of surface under the cumulative ranking curve (SUCRA). Additionally, drug class analyses were carried out. Results . Twenty three new RCTs were added to the network. IL-23 inhibitor RIS, recently approved in the Russian Federation, has joined the group of the most efficacious drugs, such as IL-17 inhibitors NTK and IXE, as well as IL-23 inhibitor GUS. In terms of PASI 75, RIS and IXE showed superiority compared to all tumor necrosis factor alpha (TNFα) inhibitors (INF, ADA, ETN), small molecules (TOFA and APR), and IL-12/23 inhibitor UST, while NTK and GUS were characterized by comparable efficacy with INF and outperformed the remaining drugs. There were no statistically significant differences in efficacy between all the TNFα inhibitors. GUS, IXE, INF, NTK, RIS and SEC demonstrated that no more than 2 patients need to be treated to achieve one PASI 75 response, and no more than 3 need to be treated for one PASI 90 response (according to the upper limit of 95% credible interval). Same as in the previously published study, NTK showed the lowest costs per responder for both 12-week and 1-year periods. Conclusion . The addition of head-to-head trials and increased statistical power of the network revealed previously unidentified significant differences between treatment options for moderate-to-severe plaque psoriasis.
Publisher: Media Sphere Publishing Group
Date: 2022
Publisher: Mediar Press
Date: 25-12-2022
DOI: 10.47360/1995-4484-2022-594-601
Abstract: Objective – to compare the clinical efficacy and cost-effectiveness of IL-17 inhibitors (SEC, IXE, NTK) in the treatment of adult patients with ankylosing spondylitis (AS) in the healthcare system of the Russian Federation.Material and methods. The study is a sub-analysis of a previously published systematic review and network meta-analysis of the comparative efficacy of biologics in adult patients with AS in the Russian Federation. NNT values were calculated for BASDAI 50 and ASAS 20/40 after 16 weeks of therapy for all studied drugs. CpR was estimated for each biologic after 16 weeks and one year of therapy. Additionally, we carried out an assessment of the financial burden of the most cost-effective strategies for the treatment of AS. Results. The use of NTK is characterized by an average of no more than three patients needed to treat to achieve one ASAS 20/40 or BASDAI 50 response, while on IXE and SEC – no more than 4–5 patients need to be treated, depending on the estimated effectiveness criterion. According to CpR estimate, NTK is the most cost-effective IL-17 inhibitor for the treatment of AS, both after 16 weeks and after one year of therapy. Conclusion. The obtained results make it possible to compare the effectiveness of IL-17 inhibitors from a clinical and economic points of view and can be used both in decision making process of treatment strategies for in idual patients, and at the population level – when deciding on the reimbursement of drugs
Publisher: Media Sphere Publishing Group
Date: 2022
Publisher: American Society for Clinical Investigation
Date: 15-02-2023
DOI: 10.1172/JCI162775
Publisher: Consilium Medicum
Date: 17-05-2023
DOI: 10.26442/18151434.2023.1.202138
Abstract: Aim. To assess the effect of febrile neutropenia (FN) prophylaxis with granulocyte colony-stimulating factors (G-CSF) in real-world cancer patients. Materials and methods. We conducted a statistical analysis of anonymized medical records collected in the Webiomed platform. Before analysis, the cards were validated by clinical experts. Electronic records were extracted according to two principles: mentioning D70 in the diagnosis or mentioning a chemotherapy regimen associated with a high risk of FN (20%), requiring the primary prevention of neutropenia. Thus, we obtained two datasets comprising 47.085 (590 patients) and 30.523 (398 patients) records, respectively. Results. Based on the analysis results, the most common risk factors for FN development were highly hematologically toxic chemotherapy regimens and elderly age about 50% in the adult population. In both datasets, the number of female patients prevailed (63.7% in dataset 1, 91.2% in dataset 2), so the most common was breast cancer. Less common were cervical cancer, digestive cancer, and lung cancer. Despite the indications for primary prevention of FN, for safety and importance of achieving the planned dose intensity, it was administered in 18.3% of patients in dataset 1 and 2.3% in dataset 2. No FN or G-CSF-related adverse events were reported in patients who received adequate primary prevention. Conclusion. Some issues related to G-CSF administration in cancer patients were identified. We identified the insufficient provision of patients with primary prevention of FN, which negatively affects survival rates and reduces adherence to antitumor therapy. Real-world data demonstrate the efficacy and safety of FN prevention and planned dose intensity maintance in cytotoxic therapy regimens.
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2022
DOI: 10.1101/2022.12.13.22283391
Abstract: Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. 64% (456/714) of participants reported poor sleep quality 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p .001) and sleep efficiency (85.4% vs 88.5%, p .001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p .001). Overall sleep quality (effect estimate 4.2 (3.0–5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0–4.5)), and sleep regularity (effect estimate 5.9 (3.7–8.1)) were associated with both dyspnoea and impaired lung function (FEV 1 and FVC). Depending on the sleep metric, anxiety mediated 13–42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Callum Jackson.