Therapies for acute myeloid leukemia in patients ineligible for standard induction chemotherapy: a systematic review.

Aim: To review clinical evidence for current and emerging treatments for patients with acute myeloid leukemia (AML) who are ineligible for first-line induction chemotherapy. Methods: A systematic literature review was performed (28 October 2021) to identify clinical outcomes including overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) and adverse events (AEs). Results: Of 233 references that met prespecified criteria, 26 studies were included. Adding targeted therapies (venetoclax/ivosidenib) to hypomethylating agents (HMAs) yielded better OS hazard ratios (HRs) (0.44-0.66) and EFS HRs (0.33-0.63) compared with other agents. AEs were more frequent with combination therapies than control arms, except with ivosidenib plus azacitidine. Conclusion: Targeted therapy combined with a HMA shows the most promising results in this difficult-to-treat population.

Acute myeloid leukemia (AML) is a type of cancer of the bone marrow and blood that leads to overproduction of immature white blood cells. High-dose (intensive) chemotherapy is usually the first treatment option for AML. However, more than half of people newly diagnosed with AML cannot receive the recommended initial intensive chemotherapy due to older age or poor health. Treatment with low-dose cytarabine (LDAC) and hypomethylating agents (HMAs), such as azacitidine, is key for such people. We reviewed 26 clinical trials looking into available and developing treatment options for people who cannot have the recommended initial chemotherapy. The review found evidence that combining LDAC or HMA with a targeted therapy can improve survival. In AML, new therapies (such as ivosidenib, venetoclax and glasdegib) 'target' specific changes in the genes of cancer cells to slow or stop their division and growth. The greatest improvement in survival was seen in clinical trials where targeted therapies were added to azacitidine or LDAC. Targeted therapies may result in certain side effects that require regular monitoring. To provide patients with the benefits of targeted therapies they need to undergo genetic testing at the time of diagnosis. Tests to determine an individual's specific gene changes allows clinicians to develop personalised treatment plans with available targeted therapies. This shows promise in improving survival for people with AML who cannot receive initial intensive chemotherapy.

Real-World Utilisation and Bleed Rates in Patients with Haemophilia B Who Switched to Recombinant Factor IX Fusion Protein (rIX-FP): A Retrospective International Analysis.

INTRODUCTION: Despite the well-documented benefits of prophylaxis, treatment burden is still a barrier to adherence in patients with haemophilia. An extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP) has been developed for the treatment of patients with haemophilia B and is indicated for dosing up to every 14 days. This analysis evaluated real-world outcomes in patients switching to rIX-FP from the previous FIX product in Italy, Belgium and the UK. METHODS: Anonymised chart data were collected from the pre-existing medical records of patients with haemophilia B between May and September 2018. Patients were included in the analysis if they had been treated with rIX-FP for ≥ 8 weeks. Data were compared between rIX-FP and the patient's prior FIX product. RESULTS: Twenty-three HTCs from Italy (n = 13), Belgium (n = 3) and the UK (n = 7) provided data for 84 male patients, 92.8% of which had severe haemophilia B. The majority of patients were previously on prophylactic regimens with their prior FIX product (Italy, 44/49; Belgium, 7/10; UK, 22/25). The switch to prophylaxis with rIX-FP led to reductions in mean annualised bleeding rate of 94.3% in Italy, 93.9% in Belgium and 67.7% in the UK compared with prior FIX prophylaxis. Overall, 41% of patients experienced zero spontaneous bleeds prior to switching, compared with 88% following the switch to rIX-FP. The majority of patients had a reduction in dosing frequency following the switch, with 98.6% of patients dosing once weekly or less frequently compared with 9.6% of patients dosing at this frequency with their prior FIX. Mean weekly FIX consumption was reduced compared with prior FIX prophylaxis. CONCLUSION: This retrospective review of real-world evidence demonstrated that switching to rIX-FP from prior FIX was associated with improved haemostatic efficacy and reduced factor consumption in patients with haemophilia B from Italy, Belgium and the UK.

While clinical trials provide robust evidence as to the effectiveness and safety of a new drug, they are tightly controlled and so may not reflect some of the issues that may be discovered in clinical practice. Therefore, real-world analyses are important to determine how a product performs in patients in everyday settings. This study looked at the use of an extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP), which was designed to allow longer dosing intervals, in patients with haemophilia B in Italy, Belgium and the UK, and compared this with the patients' previous FIX product. Anonymous patient chart data were collected from participating centres and analysed in terms of bleeding rate, factor usage and dosing frequency for rIX-FP and previous FIX product. The results showed that after switching to rIX-FP, patients experienced lower bleeding rates, lower factor usage and less frequent dosing regimens compared with their previous FIX product. This is the first analysis to assess the real-world clinical benefits of switching to prophylaxis with rIX-FP from a prior FIX product in Italy, Belgium and the UK. This study further strengthens the results seen in clinical trials with rIX-FP, confirming that the effective bleeding prevention demonstrated in clinical trials is consistent with that seen in patients in real-world clinical practice.

Characterizing high-burden rosacea subjects: a multivariate risk factor analysis from a global survey.

Objective: To characterize rosacea features suitable for identification of high-burden (HB) subjects in clinical practice.Design: Global online survey with subjects recruited using an online panel from the United States, Canada, Italy, United Kingdom, Germany and France. Subjects self-reported a physician's diagnosis of rosacea.Measurements: HB subjects were defined as those with ≥3/4 domains (quality of life, lifestyle adaptation, time trade-off, willingness to pay) greater than the median. Group characteristics were analyzed and multivariate-logistic modeling used to investigate factors most associated with HB.Results: 710 subjects completed the survey, including 158 HB subjects. HB was observed in all self-declared rosacea severities. HB subjects were more likely to spend more time daily on skin care and experienced approximately double the impact of health problems on work productivity in the past 7 days (p < .01). In the past 12 months, HB subjects were more likely to have at least one visit to the emergency room (41.8% vs 11.2%; p < .01). In the multivariate risk analysis, factors most associated with HB included rosacea severity, impact of health problems on regular daily activities and age at first symptoms.Conclusion: Rosacea has a distinct subset of HB subjects who can be successfully characterized.

Erythema of Rosacea Impairs Health-Related Quality of Life: Results of a Meta-analysis.

INTRODUCTION: The central diagnostic feature of rosacea is diffuse central-facial erythema. The objective was to summarize published and unpublished health-related quality of life (HRQoL) data from seven previous studies in rosacea patients. METHODS: A meta-analysis was performed on baseline HRQoL data of subjects with erythema of rosacea from five randomized controlled trials, one open-label safety study and one epidemiological study. The data from four questionnaires were analyzed, including the Euro QoL 5-dimension (EQ5D) generic questionnaire, the Dermatology Life Quality Index (DLQI) dermatology-specific quality of life instrument, the Productivity and Social Life Questionnaire and the Facial Redness Questionnaire. RESULTS: The global EQ5D index score was 0.859 and the domains of pain/discomfort (31.5% moderate or extreme pain) and anxiety/depression (26.4% moderate or extreme) were most affected. Worse scores were observed with erythema of rosacea in the absence of inflammatory lesions (EQ5D score of 0.832 for no lesions vs 0.919 for subjects with ≥1 lesion). Almost half (43%) the subjects had at least moderately impaired HRQoL, including 19.8% with a DLQI total score of ≥11 indicating severely impaired HRQoL; symptoms/feelings was the most affected domain. Subjects with a patient self-assessment (PSA) of severe erythema of rosacea had a worse mean DLQI score than moderate PSA subjects (8.6 vs 6.0). Work life and social life were affected, especially in subjects with severe PSA (62% with social life at least somewhat affected). CONCLUSION: Erythema of rosacea causes a marked decrease in HRQoL in most patients, especially those with self-perceived severe erythema and without inflammatory lesions, and should thus be considered as an important medical problem requiring medical intervention. FUNDING: Galderma UK.

An economic evaluation of topical treatments for actinic keratosis.

Actinic keratoses (AK) commonly occur as lesions, in sun-exposed areas. Various treatment modalities exist for their removal. We assessed the cost-effectiveness in 2007 of topical treatments (5-fluorouracil, imiquimod) and photodynamic therapy with methyl aminolevulinate (MAL-PDT) for AK under the perspective of the UK National Health Service (NHS) in England and Wales over two lines of treatment. We used a decision tree analytical approach. Efficacy data were taken from published trial literature for two investigator-assessed outcomes: 'complete clinical response' and 'excellent cosmetic outcome'. MAL-PDT at first line followed by various second-line treatments provided the greatest probability of complete clinical response (91.7%), but MAL-PDT at first line followed by further MAL-PDT as the second-line treatment provided the greatest probability of excellent cosmetic outcome (73.6%). The cost of MAL-PDT was 437 pounds sterling after two lines of treatment if MAL-PDT was that second-line treatment or 418 pounds sterling if various treatments were offered at second line. The probabilistic analysis produced consistent results. Based on this model, the costs and effectiveness of MAL-PDT in the UK NHS compare well with other treatments for AK.

Cost-effectiveness of a fixed combination of hydroquinone/tretinoin/fluocinolone cream compared with hydroquinone alone in the treatment of melasma.

BACKGROUND: A once-daily fixed combination of hydroquinone, tretinoin, and fluocinolone acetonide (Tri-luma) is a newly available treatment for melasma. OBJECTIVE: To assess cost-effectiveness of triple combination therapy (TCT) applied once daily and hydroquinone alone applied twice daily in the U.S., Argentina, Brazil, Chile, and Colombia from a payer's perspective. METHODS: Clinical data and utilization of key health resources (medication only) were assessed within an 8-week clinical trial conducted in Brazil. Total cost per primary success (complete clearing) was used to compare each treatment with not treating and incremental cost effectiveness ratios were used to compare between treatments. RESULTS AND CONCLUSION: TCT had a 30% better rate of complete clearing than hydroquinone with a lower cost in the U.S. and an incremental cost in other countries. In every country, cost per primary success was lower for TCT than for hydroquinone. Results were robust to varying assumptions of success rates and quantity used.

Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy.

A risk assessment tool (OsteoRisk) for identifying Latin American women with osteoporosis.

OBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scoresor=50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS: A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index <=-2; 65.6% were osteoporotic), moderate-risk patients (-2< index <=1; 26.7% were osteoporotic), and low-risk patients (index>1; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil. CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.