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F1000Research 2019Paget's disease is a condition which continues to challenge and surprise. The dramatic fall in its incidence over the last three decades has been an enormous surprise,... (Review)
Review
Paget's disease is a condition which continues to challenge and surprise. The dramatic fall in its incidence over the last three decades has been an enormous surprise, as is the capacity of a single infusion of the potent bisphosphonate, zoledronate, to produce biochemical remission in 90% of patients, remissions which usually persist for many years and raise the possibility of a cure in some patients. However, challenges in its management remain. The trials carried out in Paget's disease have almost always had biochemical indices as their primary endpoints. From these studies, we also know that bone pain is relieved, quality of life improved, bone histology normalised, and radiological lesions healed. Thus, disease progression is halted. Studies have not been powered to assess whether clinically important endpoints such as fracture and the need for joint replacement surgery are diminished, although these complications are well established as part of the natural history of the condition. Since disease progression is prevented by potent bisphosphonates, it is likely that disease complications will also be prevented. Zoledronate also reduces the frequency of follow-up needed and therefore provides a very cost-effective intervention in those who have symptomatic disease or are at risk of complications.
Topics: Clinical Trials as Topic; Diphosphonates; Disease Management; Disease Progression; Humans; Osteitis Deformans; Quality of Life; Remission Induction; Zoledronic Acid
PubMed: 31489180
DOI: 10.12688/f1000research.19676.1 -
Frontiers in Oncology 2021Relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) is an unfavorable event associated with a poor prognosis,... (Review)
Review
Relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) is an unfavorable event associated with a poor prognosis, particularly for patients with early relapses. It usually arises from resistant leukemic blasts that escaped both preparative chemotherapy regimen and the graft-versus-leukemia (GVL) effect. Independent from the choice of salvage treatment, only minority of patients can achieve durable remissions. In recent years, better understanding of the disease relapse biology post allo-HCT allowed the application of newer strategies that could induce higher rates of remission, and potential longer survival. Those strategies aim at optimizing drugs that have a direct anti-leukemia activity by targeting different oncogenic mutations, metabolism pathways or surface antigens, and concurrently enhancing the immune microenvironment to promote GVL effect. This review discusses the current treatment landscape of AML relapse post allo-HCT.
PubMed: 35047405
DOI: 10.3389/fonc.2021.793274 -
Journal of Medical Economics Jun 2015To determine the short-term costs per sustained remission and sustained response of three tumor necrosis factor inhibitors (infliximab, adalimumab, and golimumab) in...
OBJECTIVE
To determine the short-term costs per sustained remission and sustained response of three tumor necrosis factor inhibitors (infliximab, adalimumab, and golimumab) in comparison to conventional therapy for the treatment of moderately-to-severely active ulcerative colitis.
METHODS
A probabilistic Markov model was developed. This included an 8-week induction period, and 22 subsequent 2-week cycles (up to 1 year). The model included three disease states: remission, response, and relapse. Costs were from a Canadian public payer perspective. Estimates for the additional cost per 1 year of sustained remission and sustained response were obtained.
RESULTS
Golimumab 100 mg provided the lowest cost per additional remission ($935) and cost per additional response ($701) compared with conventional therapy. Golimumab 50 mg yielded slightly higher costs than golimumab 100 mg. Infliximab was associated with the largest additional number of estimated remissions and responses, but also higher cost at $1975 per remission and $1311 per response. Adalimumab was associated with the largest cost per remission ($7430) and cost per response ($2361). The cost per additional remission and cost per additional response associated with infliximab vs golimumab 100 mg was $14,659 and $4753, respectively.
CONCLUSIONS
The results suggest that the additional cost of 1 full year of remission and response are lowest with golimumab 100 mg, followed by golimumab 50 mg. Although infliximab has the highest efficacy, it did not exhibit the lowest cost per additional remission or response. Adalimumab produced the highest cost per additional remission and response.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Canada; Colitis, Ulcerative; Cost-Benefit Analysis; Humans; Infliximab; Markov Chains; Models, Econometric; Quality-Adjusted Life Years; Recurrence; Remission Induction; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 25629655
DOI: 10.3111/13696998.2015.1012513 -
Journal of the American Society of... Mar 2017Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag...
Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy-proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4-3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.
Topics: Cohort Studies; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Prognosis; Proteinuria; Remission Induction; Time Factors; Treatment Outcome
PubMed: 27756808
DOI: 10.1681/ASN.2015111262 -
Cancer Immunology, Immunotherapy : CII Oct 2001A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the... (Review)
Review
CONTEXT
A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made.
OBJECTIVE
To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever.
CONCLUSION
Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.
Topics: Adult; Antigens, Neoplasm; Bacterial Toxins; Bacterial Vaccines; Erysipelas; Female; Fever; Heat-Shock Proteins; Humans; Hyperthermia, Induced; Immunotherapy; Immunotherapy, Active; Infections; Injections, Intralesional; Male; Mesoderm; Neoplasms; Remission Induction; Remission, Spontaneous; Sarcoma; Sex Factors; Soft Tissue Neoplasms; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pyogenes; T-Lymphocyte Subsets; Treatment Outcome; Urinary Bladder Neoplasms; Urinary Tract Infections
PubMed: 11726133
DOI: 10.1007/s002620100216 -
Cancers Dec 2023The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML).... (Review)
Review
The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30-40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials. In this review, we will discuss current studies assessing the efficacy of frontline regimens integrating VEN into intensive chemotherapy in younger patients with AML and specific molecularly defined subgroups.
PubMed: 38201501
DOI: 10.3390/cancers16010073 -
Cureus Oct 2020Ulcerative colitis (UC) is primarily a disease of non-smokers or ex-smokers. Since there have been previous claims of the beneficial effects of transdermal nicotine,... (Review)
Review
Ulcerative colitis (UC) is primarily a disease of non-smokers or ex-smokers. Since there have been previous claims of the beneficial effects of transdermal nicotine, researchers studied its efficacy to include it in the treatment regimen: to prevent remissions and as maintenance therapy. This review aims to evaluate the efficacy of transdermal nicotine as a treatment option for mild to moderately active ulcerative colitis. We shortlisted 22 articles after a careful analysis and elimination process. These articles were reviewed and analyzed, and it was found that transdermal nicotine in combination with conventional therapy was more beneficial than individual treatment with either. Further controlled studies evaluating the appropriate dosage for remission and maintenance treatment needs to be done.
PubMed: 33240692
DOI: 10.7759/cureus.11096 -
Therapeutic Advances in Hematology 2022The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in... (Review)
Review
The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in combination with the hypomethylating agent azacitidine improved rates of response and measurable residual disease (MRD)-negative remissions in addition to overall survival in the pivotal phase 3 VIALE-A trial compared with azacitidine monotherapy and has since emerged as the current standard of care in older or unfit patients with AML. In younger, fit patients with AML, intensive induction and consolidation chemotherapy (IC) is commonly employed as frontline therapy; however, relapse remains the principal cause of treatment failure in approximately 30-40% of patients. Improved IC regimens that increase MRD-negative response rates, result in durable remissions, and enable transition to curative allogeneic hematopoietic stem cell transplantation in appropriate patients remain an area of active inquiry. Preliminary results from trials investigating the combination of VEN with IC have reported promising findings to date, with composite complete remission and MRD-negative remission rates of approximately 89-94% and 82-93%, respectively, correlating with improved 12-month event-free and overall survival compared to historical outcomes with IC. Herein, we discuss ongoing trials investigating VEN in combination with IC in addition to outcomes within specific molecularly defined subgroups; review the molecular mechanisms of sensitivity and resistance to VEN, and highlight future combinations of VEN with novel targeted therapies for the treatment of AML.
PubMed: 35510212
DOI: 10.1177/20406207221093964 -
Diabetologia Oct 2020Approximately 10% of total healthcare budgets worldwide are spent on treating diabetes and its complications, and budgets are increasing globally because of ageing... (Randomized Controlled Trial)
Randomized Controlled Trial
Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management programme.
AIMS/HYPOTHESIS
Approximately 10% of total healthcare budgets worldwide are spent on treating diabetes and its complications, and budgets are increasing globally because of ageing populations and more expensive second-line medications. The aims of the study were to estimate the within-trial and lifetime cost-effectiveness of the weight management programme, which achieved 46% remissions of type 2 diabetes at year 1 and 36% at year 2 in the Diabetes Remission Clinical Trial (DiRECT).
METHODS
Within-trial analysis assessed costs of the Counterweight-Plus intervention in DiRECT (including training, programme materials, practitioner appointments and low-energy diet), along with glucose-lowering and antihypertensive medications, and all routine healthcare contacts. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of remissions, assuming continued relapse rates as seen in year 2 of DiRECT and consequent life expectancy, quality of life and healthcare costs.
RESULTS
Mean total 2 year healthcare costs for the intervention and control groups were £3036 and £2420, respectively: an incremental cost of £616 (95% CI -£45, £1269). Intervention costs (£1411; 95% CI £1308, £1511) were partially offset by lower other healthcare costs (£796; 95% CI £150, £1465), including reduced oral glucose-lowering medications by £231 (95% CI £148, £314). Net remission at 2 years was 32.3% (95% CI 23.5%, 40.3%), and cost per remission achieved was £1907 (lower 95% CI: intervention dominates; upper 95% CI: £4212). Over a lifetime horizon, the intervention was modelled to achieve a mean 0.06 (95% CI 0.04, 0.09) QALY gain for the DiRECT population and mean total lifetime cost savings per participant of £1337 (95% CI £674, £2081), with the intervention becoming cost-saving within 6 years.
CONCLUSIONS/INTERPRETATION
Incorporating the lifetime healthcare cost savings due to periods of remission from diabetes and its complications, the DiRECT intervention is predicted to be both more effective (QALY gain) and cost-saving in adults with type 2 diabetes compared with standard care. This conclusion appears robust to various less favourable model scenarios, providing strong evidence that resources could be shifted cost-effectively to support achieving remissions with the DiRECT intervention.
TRIAL REGISTRATION
ISRCTN03267836 Graphical abstract.
Topics: Antihypertensive Agents; Caloric Restriction; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Health Care Costs; Humans; Hypoglycemic Agents; Male; Middle Aged; Obesity; Obesity Management; Overweight; Quality-Adjusted Life Years; Remission Induction; United Kingdom
PubMed: 32776237
DOI: 10.1007/s00125-020-05224-2 -
Blood Reviews Sep 2018The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is... (Review)
Review
The International Working Group (IWG) response criteria for acute myeloid leukemia, published in 2003, have remained the standard by which the efficacy of new drugs is measured in clinical trials. Over the last decade, concepts related to treatment response have been challenged by several factors; for example, the dissociation between early clinical response and survival outcome in older patients, the recognition that epigenetic and newer differentiating-agent therapies may produce delayed responses and also hematologic improvement/transfusion independence without a morphologic response, and evidence that remissions without minimal (or measurable) residual disease (MRD) may result in outcomes superior to those of morphologic remissions with persistent MRD. The evolving role of MRD status as a potential surrogate for predicting long-term survival has enhanced the clinical need to standardize and incorporate emerging technologies that enable deeper responses beyond those recognized by the IWG, and to pre-emptively identify patients at risk of early relapse. The potential for therapeutic interventions to erase MRD and alter the natural history represents an important and open research question. Reviewed here are some of the implications and challenges associated with establishing and incorporating new treatment response criteria, initially into clinical research, and eventually into real-world practice.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Prognosis; Remission Induction; Treatment Outcome
PubMed: 29706486
DOI: 10.1016/j.blre.2018.03.006