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Blood Mar 2015We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org),... (Review)
Review
We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Decision Making; Diffusion of Innovation; Economics, Medical; Hematologic Neoplasms; Humans; Models, Economic; Quality of Life; Quality-Adjusted Life Years; Registries; Treatment Outcome
PubMed: 25655601
DOI: 10.1182/blood-2014-07-592832 -
Cancer Treatment Reviews Dec 2012Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL.
METHODS
We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option.
RESULTS
Five RCTs were included in our comparison network. Overall, patients were younger (59-65 years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32).
CONCLUSION
Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Randomized Controlled Trials as Topic; Rituximab; Vidarabine
PubMed: 22405931
DOI: 10.1016/j.ctrv.2012.02.006 -
Systematic Reviews Oct 2021The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in... (Review)
Review
PURPOSE
The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.
METHODS
A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.
RESULTS
A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.
CONCLUSIONS
Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID CRD42020106886.
Topics: Africa; Humans; Multiple Sclerosis
PubMed: 34711264
DOI: 10.1186/s13643-021-01782-7 -
The Cochrane Database of Systematic... Dec 2013This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of... (Review)
Review
BACKGROUND
This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to secondary progressive MS. MS causes a major socioeconomic burden for the individual patient and for society. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and help to reduce the socioeconomic burden of MS. Alternative and more effective MS treatments with new modes of action and good safety are needed to expand the current treatment repertoire. It has been shown that B lymphocytes are involved in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell depletion therapy in the treatment of RRMS.
OBJECTIVES
The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) (interferon-β (IFN-β), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to reduce disease activity for people with RRMS were assessed.
SEARCH METHODS
The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (9 August 2013). We checked the references in identified trials and manually searched the reports (2004 to August 2013) from neurological associations and MS societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec and Roche.
SELECTION CRITERIA
All randomised, double-blind, controlled parallel group clinical trials with a length of follow-up equal to or greater than one year evaluating rituximab, as monotherapy or combination therapy, versus placebo or approved DMDs for patients with RRMS without restrictions regarding dosage, administration frequency and duration of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures of The Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. Principal investigators of included studies were contacted for additional data or confirmation of data.
MAIN RESULTS
One trial involving 104 adult RRMS patients with an entry score ≤ 5.0 on the Expanded Disability Status Scale (EDSS) and at least one relapse during the preceding year was included. This trial evaluated rituximab as monotherapy versus placebo, with a single course of 1000 mg intravenous rituximab (on day 1 and day 15). A significant attrition bias was found at week 48 (24.0%). Patients receiving rituximab had a significant reduction in total number of gadolinium-enhancing lesions at week 24 (mean number 0.5 versus 5.5; relative reduction 91%) and in annualised rate of relapse at week 24 (0.37 versus 0.84) but not at week 48 (0.37 versus 0.72). Disability progression was not included as an outcome in this trial. More patients in the rituximab group had adverse events within the 24 hours after the first infusion (78.3% versus 40.0%), such as chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to-moderate events (92.6%). The most common infection-associated adverse events (> 10% in the rituximab group) were nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. Among them, only urinary tract infections (14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. One ongoing trial was identified.
AUTHORS' CONCLUSIONS
There is not sufficient evidence to support the use of rituximab as a disease-modifying therapy for RRMS because only one RCT was included. The quality of the study was limited due to high attrition bias, the small number of participants, and short follow-up. The beneficial effects of rituximab for RRMS remain inconclusive. However, short-term treatment with a single course of rituximab was safe for most patients with RRMS. Mild-to-moderate infusion-associated adverse events were common, as well as nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. The potential benefits of rituximab for treating RRMS need to be evaluated in large-scale studies that are of high quality along with long-term safety.
Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Humans; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic; Rituximab
PubMed: 24310855
DOI: 10.1002/14651858.CD009130.pub3 -
The Journal of Heart and Lung... Sep 2017Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is... (Comparative Study)
Comparative Study Review
BACKGROUND
Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is the most common form. This systematic review sought to identify the current evidence base for CLAD-BOS therapies after initial immunosuppressive treatment strategies.
METHODS
The MEDLINE, Embase, and Cochrane Library databases from inception to May 3, 2016, were searched using keywords relating to CLAD-BOS, study designs, and treatments of interest, including extracorporeal photopheresis (ECP), aerosolized cyclosporine, total lymphoid irradiation (TLI), alemtuzumab, and montelukast. Titles, abstracts, and full texts were screened by 2 independent reviewers to identify studies of CLAD-BOS second-line therapy in adult lung transplant patients. Quality was assessed according to the Downs and Black checklist.
RESULTS
Of the 936 individual citations identified, 47 reports of 40 studies met inclusion criteria, including 17 full publications, 11 recent (2015-2016), and 12 older (pre-2015) congress proceedings. Most of the full publications and recent abstracts investigated ECP (n = 11), TLI (n = 5), alemtuzumab (n = 4), and montelukast (n = 2). Most studies were uncontrolled and retrospective. Compared with standard therapy alone, improved lung function and survival was reported for ECP in 2 studies without randomization, with lower-quality evidence for improved lung function for TLI, montelukast, and aerosolized cyclosporine.
CONCLUSIONS
Because most identified studies were of retrospective and uncontrolled design, comparison of treatment effects was limited. Available evidence suggests stabilized lung function after ECP in combination with established immunosuppressive regimens in late-line CLAD-BOS treatment, with fewer data for TLI, montelukast, and aerosolized cyclosporine.
Topics: Allografts; Bronchiolitis Obliterans; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Lung Transplantation; Lymphatic Irradiation; Male; Photopheresis; Primary Graft Dysfunction; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Syndrome; Transplantation Immunology; Treatment Outcome
PubMed: 28662986
DOI: 10.1016/j.healun.2017.05.030 -
BioDrugs : Clinical Immunotherapeutics,... Aug 2015Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment... (Review)
Review
BACKGROUND
Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment costs impose a substantial cost burden on patients and society.
OBJECTIVES
The study aimed to systematically review cost-effectiveness evidence of mAb orphan drugs.
METHODS
Ovid MEDLINE(®), EMBASE(®), and PsycINFO(®) were searched in June 2014 and articles were selected if they conducted economic evaluations of the mAb orphan drugs that had received marketing approval in the USA. The quality of the selected studies was assessed using the Quality of Health Economic Studies (QHES) instrument.
RESULTS
We reviewed 16 articles that included 24 economic evaluations of nine mAb orphan drugs. Six of these nine drugs were included in cost-utility analysis studies, whereas three drugs were included in cost-effectiveness analysis studies. Previous cost-utility analysis studies revealed that four mAb orphan drugs (cetuximab, ipilimumab, rituximab, and trastuzumab) were found to be cost effective; one drug (bevacizumab) was not cost effective; and one drug (infliximab) was not consistent across the studies. Prior cost-effectiveness analysis studies which included three mAb orphan drugs (adalimumab, alemtuzumab, and basiliximab) showed that the incremental cost per effectiveness gained for these drugs ranged from $US4669 to $Can52,536 Canadian dollars. The quality of the included studies was good or fair with the exception of one study.
CONCLUSIONS
Some mAb orphan drugs were reported as cost effective under the current decision-making processes. Use of these expensive drugs, however, can raise an equity issue which concerns fairness in access to treatment. The issue of equal access to drugs needs to be considered alongside other societal values in making the final health policy decisions.
Topics: Antibodies, Monoclonal; Cost-Benefit Analysis; Decision Making; Drug Approval; Humans; Orphan Drug Production; Rare Diseases
PubMed: 26263903
DOI: 10.1007/s40259-015-0135-4 -
Autoimmunity Reviews Apr 2020Immune reconstitution therapy (IRT) is an emerging concept for the treatment of multiple sclerosis (MS) that is given intermittently and can induce long-term remission...
Immune reconstitution therapy (IRT) is an emerging concept for the treatment of multiple sclerosis (MS) that is given intermittently and can induce long-term remission of MS that is sustained in treatment-free periods. A systematic literature review was performed to identify and summarize current knowledge regarding the short- and long-term immunological consequences of different IRTs and CD20 depleting therapies on the cellular level in patients with MS. A total of 586 articles published between January 2010 and September 2019 were identified and screened; 44 studies met inclusion criteria for the review. All the treatments considered appeared to produce both qualitative and quantitative changes in the immune cell populations of patients with MS that resulted in a more anti-inflammatory immune profile. Autologous hematopoietic stem cell transplantation produced the longest-lasting and greatest effects on a wide range of immune cells. Many patients achieved prolonged depletion of the adaptive immune system when alemtuzumab and cladribine tablets were administered as short courses of therapy; however, a proportion of patients required retreatment to maintain these effects. Alemtuzumab may produce greater depletion of both CD4+ and CD8+ T cells than cladribine tablets, although both treatments similarly deplete B cells. Recovery of B cells before T cell recovery and hyperpopulation of B cells after alemtuzumab may contribute to secondary autoimmunity. Cladribine tablets had a greater effect on B cells than T cells, and no hyperpopulation of B cells was observed after treatment with cladribine tablets. Ocrelizumab and rituximab require regular repeated treatment every 6 months to maintain depletion of B and T cells. Effects of the drug treatments on the innate immune system were minor compared with those on the adaptive immune system. Additional characterization of the cellular changes occurring during IRT and CD20 depletion may lead to further improvement in the understanding of the pathogenesis of MS and the future development of therapies with even longer lasting effects. Although the treatments considered in this review improve quality of life and outcomes for patients with MS, a cure for this debilitating disease is not yet in sight.
Topics: Alemtuzumab; Autografts; Cladribine; Hematopoietic Stem Cell Transplantation; Humans; Immune Reconstitution; Multiple Sclerosis; Quality of Life
PubMed: 32062028
DOI: 10.1016/j.autrev.2020.102492 -
Seminars in Arthritis and Rheumatism Oct 2015To examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a... (Review)
Review
OBJECTIVE
To examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic modifier immunosuppressant treatment (NTT) currently available in clinical practice.
METHODS
A systematic search between January 2000 and April 2014 was conducted using EMBASE, Ovid MEDLINE, Evidence Based Medicine Reviews-ACP Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of NTT as a biologic modifier immunosuppressant medication for ACU, refractory to topical and/or systemic steroid therapy, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria. We determined a combined estimate of the proportion of subjects responding to NTT.
RESULTS
We initially identified 526 articles, of which 89 were potentially eligible. From the selection process, a total of 10 retrospective chart reviews and a randomized single-blind controlled study, providing a total of 12 children and 34 adults, were deemed eligible: 3 articles looked at rituximab, 3 at abatacept, 3 at tocilizumab, and the remaining 1 at alemtuzumab and the other at anakinra. Before the NTT treatment, all the eligible subjects received several combinations of one or more DMARDs and at least one anti-TNF strategy. With the exclusion of 7 adults enrolled in the RCT, 8 of 12 children and 18 of 27 adults responded to NTT treatment: 0.66 was the combined estimate of the proportion of subjects improving on NTT treatment in children (95% CI: 0.46-0.99) and in adults (95% CI: 0.49-0.84). Further statistical comparison between different NTT strategies was not possible due to the small sample size.
CONCLUSION
Although randomized controlled trials are needed, the available evidence suggests the clinical use of a NTT strategy in selected categories of ACU, refractory to previous course of immunosuppressive treatment, DMARDs, as well as anti-TNFα, in adults as well as children.
Topics: Abatacept; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Biological Products; Humans; Interleukin 1 Receptor Antagonist Protein; Rituximab; Treatment Outcome; Uveitis
PubMed: 26164255
DOI: 10.1016/j.semarthrit.2015.05.006 -
Farmacia Hospitalaria : Organo Oficial... Mar 2020To identify and describe cost-effectiveness studies that evaluate disease modifying therapies in the context of relapsing- remitting multiple sclerosis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify and describe cost-effectiveness studies that evaluate disease modifying therapies in the context of relapsing- remitting multiple sclerosis.
METHOD
A systematic review of the literature was carried out by searching MEDLINE, Embase, the Cochrane Library, LILACS, the Tufts Medical Center Cost-Effectiveness Analysis Registry, the National Health Service Economic Evaluation Database and Open Grey. The search was performed in January 2018 and covered articles published between January 2010 and December 2017. The studies reviewed were payer- perspective cost-effectiveness analyses for interferon beta-1a, interferon beta-1b, glatiramer acetate, teriflunomide, fingolimod, dimethyl fumarate, natalizumab, alemtuzumab and rituximab. The Quality of Health Economic Studies instrument was used to determine the quality of the studies reviewed. Risk of bias was assessed without a standardized tool. An analysis was made of direct costs, quality- adjusted life-years and the incremental cost-effectiveness ratio. Data extraction and evaluation of information were conducted separately by each author.
RESULTS
Four hundred one references were found; nine studies were included. A great degree of variability was identified for several methodological aspects. Two studies that applied the incremental cost- effectiveness ratio (cost) showed no first-line therapy to be cost- effective. A third study demonstrated dominance of interferon beta-1b over placebo (USD -315,109.45) and a fourth paper showed dominance of teriflunomide over interferons and glatiramer acetate (USD - 121,840.37). As regards second-line therapies, dimethyl fumarate was cost-effective in a study that compared it to glatiramer acetate and interferon beta-1a and it was dominant in another study that compared it with glatiramer acetate (USD -158,897.93) and fingolimod (USD - 92,988.97). In the third line of treatment, one study showed natalizumab to be cost-effective as compared with fingolimod, and another study showed alemtuzumab to be dominant over fingolimod (USD -49,221). A third trial demonstrated alemtuzumab to be dominant over natalizumab (USD -1,656,266.07). Many of the trials have sponsorship bias. Eight of the trials received a high QHES score.
CONCLUSIONS
The present paper shows that cost-effectiveness studies have high levels of methodological variability, some of them reaching contradictory results. As a result, it is not possible to determine which disease- modifying therapy is really cost-effective in the context of relapsingremitting multiple sclerosis.
Topics: Antibodies, Monoclonal; Antirheumatic Agents; Cost-Benefit Analysis; Humans; Immunosuppressive Agents; Multiple Sclerosis, Chronic Progressive; Quality-Adjusted Life Years
PubMed: 32452318
DOI: 10.7399/fh.11385 -
Oncology Nursing Forum Jan 2019Subcutaneous (SC) formulations for monoclonal antibodies (mAbs) must be evaluated for efficacy and safety in comparison with preexisting IV formulations to identify...
PROBLEM IDENTIFICATION
Subcutaneous (SC) formulations for monoclonal antibodies (mAbs) must be evaluated for efficacy and safety in comparison with preexisting IV formulations to identify potential benefits and risks.
LITERATURE SEARCH
This is a systematic review of clinical trials. MEDLINE®/PubMed, EMBASE, Cochrane Library, LILACS (Latin American and Caribbean Health Sciences Literature), and reference lists were searched for relevant studies.
DATA EVALUATION
Data regarding efficacy and safety were registered in a form designed for this review. Risk of bias was assessed using the Jadad scale.
SYNTHESIS
SC administration of alemtuzumab, trastuzumab, and rituximab presented therapeutic efficacy with similar safety profiles compared to their respective IV formulations, except for the higher prevalence of local adverse events following SC administration.
IMPLICATIONS FOR PRACTICE
SC mAbs require slow administration (no less than five minutes), and the injection site should be changed at each cycle. Patient guidelines should include information about expected adverse effects, signs or symptoms of side effects requiring emergency care, and how to reduce potential discomfort caused by the injection.
Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Humans; Male; Middle Aged; Neoplasms; Rituximab; Treatment Outcome
PubMed: 30547957
DOI: 10.1188/19.ONF.E38-E47