scholarly journals Pharmacoeconomic aspects of recurrent / refractory chronic lymphocytic leukemia treatment

2020 ◽  
Vol 15 (1) ◽  
pp. 73-82
Author(s):  
A. V. Rudakova ◽  
E. A. Stadnik
Keyword(s):  
Sensitivity Analysis ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Healthcare System ◽  
Time Horizon ◽  
Budget Impact ◽  
Lymphocytic Leukemia ◽  
Number Of Patients ◽  
The Cost ◽  
Basic Version

Background. Currently, treatment of recurrent / refractory chronic lymphocytic leukemia (CLL) involves the appointment of regimens with innovative drugs, which include ibrutinib and a combination of venetoclax and rituximab. Wherein said combination provides continuing over time high frequency eradication of minimal residual disease. Thereby, this regimen can be canceled if patients do not progress after 2 years from therapy start.The objective of the study was to assess the pharmacoeconomic aspects of therapy with venetoclax and rituximab combination in patients with recurrent / refractory CLL compared with ibrutinib monotherapy.Materials and methods. Analysis was performed by a simulation method from a position of the health care system. In accordance with network meta-analysis results of clinical studies in the recurrent / refractory CLL treatment (MURANO for venetoclax + rituximab combination and RESONATE and HELIOS for ibrutinib), which showed the absence of statistically significant differences in progression-free and overall survival between these treatment options, the cost-minimization method was used in the analysis. In the basic version, the model time horizon is 4 years. The price of venetoclax, rituximab and ibrutinib in the calculation corresponded to that registered (for rituximab – the median of the registered prices) with the value-added tax and the weighted average wholesale allowance taking into account the population in Russia.When analyzing the healthcare system budget impact, the time horizon of the study was 4 years. Therapy with combination of venetoclax + rituximab starting from the first year was suggested in 100 % of newly identified recurrent / refractory CLL patients. In the base case, it was estimated that 100 patients would need therapy every year.In the basic version of analysis, the cost of therapy after progression was not taken into account. In sensitivity analysis, an option taking into account therapy cost after progression, suggesting the appointment of venetoclax in the ibrutinib group and ibrutinib in the venetoclax + rituximab group, was also evaluated. In addition, variants with disease progression were additionally evaluated in 15 % of patients per year in the venetoclax therapy group at the end of the 2-year treatment course, as well as with an increase and decrease in the disease progression rate by 15 % in both comparison groups.As part of the sensitivity analysis, an assessment is made of a 15 % decrease and increase in Venetoclax price, a 30 % decrease in Ibrutinib price compared to registered price and the option with a 3-year study time horizon. When analyzing the budget impact, options with an increase in the number of patients annually identified and requiring treatment by 10, 20, 30 and 50 % were evaluated. Clinical and economic analysis was carried out with a discount rate of 3.5 % per year. A budget impact analysis was performed without discounting.Results. According to the results of cost-effectiveness analysis in the basic version, a regimen including venetoclax can reduce costs by 46.3 % compared with ibrutinib (cost for 4 years per patient is 10.422 and 19.413 million rubles, respectively). Therapy with combination of venetoclax + rituximab in 100 newly identified recurrent / refractory CLL patients annually instead of ibrutinib monotherapy will result in a reduction in therapy costs by 29.0 %, or by 1.579 billion rubles for 4 years per 100 patients starting therapy annually. The sensitivity analysis demonstrated the high reliability of the results. Conclusion. The treatment of recurrent / refractory CLL with a combination of venetoclax and rituximab is comparable in clinical efficacy with ibrutinib monotherapy and can significantly reduce the cost of the healthcare system, and therefore increase the availability of innovative therapy for this group of patients.

scholarly journals The cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab

2019 ◽  
Vol 21 (2) ◽  
pp. 29-32
Author(s):  
Alla V Rudakova ◽  
Vladimir V Strugov
Keyword(s):  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Chronic Lymphocytic Leukemia ◽  
Time Horizon ◽  
Indirect Comparison ◽  
Weighted Average ◽  
Lymphocytic Leukemia ◽  
High Rate ◽  
Base Case ◽  
The Cost

Background. Current treatment of relapsed/refractory chronic lymphocytic leukemia implies the use of regimens that include innovative drugs such as ibrutinib and a combination of venetoclax with rituximab. Herewith the combination of venetoclax with rituximab provides a high rate of eradication of minimal residual disease and, in contrast to ibrutinib, in the standard version it is canceled after 2 years from the start of therapy. Aim. Evaluation of the cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax + rituximab and ibrutinib. Materials and methods. The evaluation was carried out from a position of the health care system using the Markov model. The study’s time horizon was 4 years. There were no statistically significant differences in overall and progression-free survival according to data of an indirect comparison of the study MURANO for the combination of venetoclax + rituximab and the studies RESONATE and HELIOS for ibrutinib. Venetoclax price (excluding VAT) used for calculation was corresponded to the manufacturer's price list and it was: film coated tablets, 10 mg №14 - 5830.2 rubles; 50 mg №7 - 14 576.86 rubles; 100 mg №7 - 29 152.65 rubles; 100 mg №14 - 58 306.37 rubles; 100 mg №112 - 466 446.67 rubles. Prices for rituximab and ibrutinib were corresponded to a median of the prices quoted. In all cases the analysis considered VAT and weighted average wholesale surcharge given population size in the Russian Federation. In the base case, costs of therapy after a transition to progression were not considered. When carrying out the sensitivity analysis, the option of monotherapy with venetoclax in patients who had progression on ibrutinib and monotherapy with ibrutinib in patients who had progression on venetoclax + rituximab was also evaluated. As part of the sensitivity analysis, a decrease and increase in the price of venetoclax by 15% and a decrease in the price of ibrutinib by 30% were also evaluated. In addition, an increase in a proportion of patients who moved to progression followed venetoclax withdrawal after 2 years of therapy was evaluated, by 15% per year, as well as a change in a frequency of progression by 15% compared with the base case and a decrease in the study’s time horizon to 3 years. The analysis was performed with discounting at 3.5% per year. Results. The analysis showed that the use of a regimen that includes venetoclax reduces the cost volume by on average of 31.3% compared to ibrutinib (the cost volume for 1 patient per 4 years - 13.341 million rubles and 19.413 million rubles, respectively). The sensitivity analysis demonstrated a reliability of the data obtained (with all analyzed modeling options, including options with an increase in venetoclax price by 15%, a decrease in ibrutinib price by 30% and a decrease in the study’s time horizon to 3 years, the combination of venetoclax + rituximab reduces costs by 1.9-41.0%). Conclusions. Treatment of relapsed / refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab is comparable in clinical efficacy with ibrutinib monotherapy and can reduce the cost and, therefore, increase the availability of innovative therapy for this group of patients. The main contribution to cost reduction is made by the fact that treatment with venetoclax and rituximab in the absence of progression stops 2 years after the start of treatment, and is not performed until the response is lost, as in the case of ibrutinib.

scholarly journals Pharmacoeconomic aspects of the therapy for moderate and severe psoriatic arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. 116-123
Author(s):  
A. V. Rudakova ◽  
D. G. Tolkacheva ◽  
V. D. Sokolova
Keyword(s):  
Cost Effectiveness ◽  
Healthcare System ◽  
Time Horizon ◽  
Impact Analysis ◽  
Budget Impact ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Effectiveness Analysis ◽  
The Russian Federation ◽  
The Cost

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.

scholarly journals Long-Term Sustained Responses Following Ibrutinib Discontinuation after Frontline Therapy with Obinutuzumab Plus Ibrutinib in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Paula A. Lengerke Diaz ◽  
Michael Y. Choi ◽  
Eider F. Moreno Cortes ◽  
Jose V. Forero ◽  
Juliana Velez-Lujan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Grade 3

Single oral targeted therapies have emerged as a standard of care in chronic lymphocytic leukemia (CLL). However, accessibility, side effects, and financial burden associated with long term administration limit their clinical use. Mainly, it is unclear in what clinical situation discontinuation of oral therapy can be recommended. The combination of type II anti-CD20 antibody obinutuzumab-Gazyva® with ibrutinib (GI) has shown a significant progression-free survival benefit in patients (pts) with CLL, including those with high-risk genomic aberrations. We conducted a phase 1b/2, single-arm, open-label trial to evaluate the safety and efficacy of GI as first-line treatment in 32 CLL pts. We report the outcome in pts that discontinued ibrutinib (either after 3 years of sustained complete response (CR) as stipulated in the clinical protocol, or due to other reasons). CLL pts enrolled in this protocol were ≥65 years old, or unfit/unwilling to receive chemotherapy. Pts received GI for six cycles, followed by daily single-agent ibrutinib. The protocol was designed to ensure that pts with a sustained CR after 36 months were allowed to discontinue ibrutinib. The median age was 66 years (IQR 59-73), and 6% of the evaluated pts had 17p deletion. All pts were able to complete the six planned cycles of obinutuzumab. The combination regimen was well-tolerated, and the most common adverse events (>5% CTCAE grade 3-4) were neutropenia, thrombocytopenia, and hyperglycemia. The rate and severity of infusion-related reactions (IRR) were much lower than expected (Grade≥ 3, 3%), and pts without IRR had lower serum levels of cytokines/chemokines CCL3 (P=0.0460), IFN-γ (P=0.0457), and TNF-α (P=0.0032) after infusion. The overall response rate was 100%, with nine pts (28%) achieving a CR, and four pts (12.5%) with undetectable minimal residual disease (uMRD) in the bone marrow, defined as <10-4 CLL cells on multicolor flow cytometry. At a median follow-up of 35.5 months (IQR 24.5-42.7) after starting treatment, 91% of the enrolled pts remain in remission with a 100% overall survival. Sixteen pts have completed a long-term follow-up of 36 months. Six pts showed CR, with three of them achieving uMRD in the bone marrow. Ten of these pts were in PR, and only one had disease progression and started treatment for symptomatic stage I disease with obinutuzumab plus venetoclax. In total, thirteen pts (41%) have stopped ibrutinib, with a median time on treatment prior to discontinuation of 35 months. Five (16%) of these pts had CRs and discontinued after 36 months. Eight additional pts (25%) had PRs and discontinued ibrutinib without being eligible: three pts discontinued prior to 36 months due to toxicities, and five pts discontinued after 36 months (3 due to side effects, and 2 due to financially driven decision). One patient eligible to discontinue ibrutinib, decided to remain on treatment despite sustained CR. After a median follow up time following ibrutinib discontinuation of 8 months (IQR 3.5-17), only two out of 13 pts have progressed (10 and 17 months after Ibrutinib discontinuation). None of the pts that stopped ibrutinib after achieving a CR have shown signs of disease progression. Of note, the pharmaceutical sponsor provided ibrutinib for the first 36 months, after which pts or their insurer became financially responsible. This particular scenario could bias the discontinuation pattern compared to a real world experience. It also provided us with a perspective about diverse factors affecting the treatment choices of pts. In summary, the obinutuzumab plus ibrutinib combination therapy was well-tolerated, with a much lower IRR rate. Efficacy compares favorably with historical controls with all pts responding to therapy, no deaths associated with treatment or disease progression, and a longer than expected time-to-progression after discontinuation of ibrutinib. The rate of ibrutinib discontinuation was higher than reported in the literature, most likely influenced by the protocol design and financial decisions driven by the switch from sponsor-provided ibrutinib to insurance or self-paid medication. Our observations regarding safety, efficacy and lack of disease progression after ibrutinib discontinuation are encouraging, and warrant confirmation in long-term prospective studies. Clinicaltrials.gov Identifier NCT02315768. Funding: Pharmacyclics LLC. Disclosures Choi: AbbVie: Consultancy, Speakers Bureau. Amaya-Chanaga:AbbVie: Ended employment in the past 24 months, Other: Research performed while employed as an investigator of this study at UCSD.. Kipps:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding.

Relevance of CD49d and CD38 expressions as predictors of disease progression in chronic lymphocytic leukemia

2018 ◽  
Vol 43 (2) ◽  
pp. 88 ◽  
Author(s):  
AmanyH Abdelrahman ◽  
MonaH Ibrahim ◽  
MahmoudT Hamza ◽  
OlaM Eid ◽  
EmanM Hassan ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Lymphocytic Leukemia

scholarly journals Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4259-4264 ◽  
Author(s):  
M Sarfati ◽  
S Chevret ◽  
C Chastang ◽  
G Biron ◽  
P Stryckmans ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Disease Progression ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Study Entry ◽  
Clinical Staging ◽  
Soluble Cd23

Abstract Prognosis of B-cell chronic lymphocytic leukemia (CLL) is based on clinical staging whose limitation is the failure to assess whether the disease will progress or remain stable in early stage (Binet A, or Rai 0, I, II) patients. We previously reported that soluble CD23 (sCD23), a protein derived from the B-cell membrane CD23 Ag, is selectively elevated in the serum of CLL patients. This prospective study assessed the predictive value of serum sCD23 level measured at study entry on the overall survival of all CLL patients and on disease progression of stage Binet A patients. Prognostic value of repeated measurements of sCD23 over time in stage A patients was also analyzed. One hundred fifty-three CLL patients were prospectively followed with a median follow-up of 78 months. Eight clinical or biological parameters were collected from the date of the first sCD23 measurement. At study entry, by Cox model, Binet staging (P = .0001) and serum sCD23 level (P = .03) appeared as prognostic factors for survival. Patients with sCD23 level above median value (> 574 U/mL) had a significantly worse prognosis than those with lower values (median survival of 53 v 100+ months, P = .0001). During follow-up, sCD23 doubling time increased by 3.2 the risk of death (P = .001). Among stage A patients (n = 100), sCD23 determination at study entry was the sole variable predictive of disease progression, patients with sCD23 level above 574 U/mL had a median time progression of 42 months versus 88 months for those with lower levels (P = .0001). Stage A patients who doubled their sCD23 level exhibited a 15-fold increased risk of progression (P = .0001) and, in addition, the sCD23 increase preceded by 48 months disease progression. We conclude that in CLL patients, serum sCD23 level provides significant additional prognostic information in terms of overall survival. Most interestingly, among early stage patients, sCD23 determination at diagnosis and during the course of the disease may help to the early identification of patients who will rapidly progress to upper stages.

Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Donald W. Milligan ◽  
Savio Fernandes ◽  
Ranjit Dasgupta ◽  
Faith E. Davies ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Free Survival ◽  
Number Of Patients ◽  
Disease Free

Abstract We have assessed autologous stem cell transplantation after treatment with fludarabine in previously untreated patients with chronic lymphocytic leukemia (CLL). This study is the first to enroll previously untreated patients and follow them prospectively. The initial response rate to fludarabine was 82% (94 of 115 patients). Stem cell mobilization was attempted in 88 patients and was successful in 59 (67%). Overall 65 of 115 patients (56%) entered into the study proceeded to autologous transplantation. The early transplant-related mortality rate was 1.5% (1 of 65 patients). The number of patients in complete remission after transplantation increased from 37% (24 of 65) to 74% (48 of 65), and 26 of 41 patients (63%) who were not in complete remission at the time of their transplantation achieved a complete remission after transplantation. The 5-year overall and disease-free survival rates from transplantation were 77.5% (CI, 57.2%-97.8%) and 51.5% (CI, 33.2%-69.8%), respectively. None of the variables examined at study entry were found to be predictors of either overall or disease-free survival. Sixteen of 20 evaluable patients achieved a molecular remission on a polymerase chain reaction (PCR) for immunoglobulin heavy-chain gene rearrangements in the first 6 months following transplantation. Detectable molecular disease by PCR was highly predictive of disease recurrence. It is of concern that 5 of 65 (8%) patients developed posttransplant acute myeloid leukemia/myelodysplastic syndrome. (Blood. 2005;105:397-404)

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