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A strong association between family history of 

 (CKD) and increased susceptibility of CKD was found among Dutch patients, suggesting that genetics play a key role in CKD risk, according to a recent study.

The authors of the study, published in the 

said that the results could make it easier for physicians to detect early-stage CKD and better identify which patients carry a greater risk of developing the disease. Researchers also said that they wanted to establish CKD heritability and detect potential disease biomarkers.

CKD is a recognized global public health problem affecting between 3.3% and 17.3% of adults in Europe, the authors noted. Established risk factors, such as hypertension and diabetes, can explain between 50% and 70% of cases. Familial clustering of CKD and kidney-related markers could suggest that genetic factors or shared environmental factors could aid CKD pathogenesis.

Researchers noted that previous research has left many knowledge gaps regarding CKD predictability and genetic influence, saying that most studies analyzing genetic factors focused on patients with late-stage kidney disease, leading to kidney failure, rather than on early-stage CKD. A focus on detecting CKD earlier could help health care providers stratify risks of CKD development and better predict the disease.

The cross-sectional study contained baseline data from the LifeLines Cohort Study and Biobank, a 

 that began in 2006 with plans to follow 3 generations for up to 30 years. The project, containing information on more than 167,500 subjects from the northern Netherlands, was established as a resource for research on complex interactions between environmental, phenotypic, and genomic factors in the development of chronic diseases and healthy aging.

Participants had an initial 2 visits at a research site, including a physical examination and blood and urine collection, and have been invited back for additional exams every 5 years.

For the current study, investigators included 155,911 patients aged 8 or older with creatinine data available in their analysis. There were 29,703 family clusters and 39,836 individual subjects included. Creatinine data was used to estimate the glomerular filtration rate (eGFR).

Overall, more than 95% of the subjects were white and 58.1% were women. The mean age of the subjects was 43.1 (14.7) years. Male participants had a slightly less favorable renal risk profile compared to female participants but had similar distributions in CKD risk and kidney markers.

Investigators observed that participants with a first-degree relative with the disease had a 3-fold greater risk for CKD compared to the general population, independent of body mass index, hypertension, diabetes, hypercholesterolemia, history of cardiovascular disease, and smoking status (recurrence risk ratio [RRR], 3.04; 95% CI, 2.26-4.09).

Across all participants, 1862 cases of CKD with an eGFR of greater than 60 mL/min/173 m2 (CKDSCr) were observed, which translated into a 1.19% crude prevalence rate. Among the family clusters, 1725 families (5.8%) had at least 1 case of CKD

. Among individuals, 2111 (5.30%) participants had at least 1 first-degree relative with CKD

, including 1680 with at least 1 parent affected, 56 with at least 1 affected offspring, and 499 with at least 1 affected sibling.

CKD defining traits that investigators reported heritability estimates were eGFR (44%), urinary albumin excretion (20%), and urinary albumin-creatinine ratio (19%). Investigators also identified heritability estimates for kidney biomarkers, serum urea (31%), serum creatinine (37%), and uric acid (48%) as well as serum electrolytes, potassium (28%), calcium (27%), and sodium (22%).

Additionally, the investigators found that participants with an affected spouse had a 1.56-fold higher risk for CKD (RRR 1.56; 95% CI, 1.20-1.96), suggesting that shared environmental factor and/or assertive mating could somewhat contribute to CKD risk.

“The data presented in this study inform future work on risk stratification based on family history, and provide a step forward in disentangling genetic and environmental risk factors in CKD,” wrote the investigators.

Some of the limitations identified by the researchers related to a lack of gold standard 24-hour albuminuria measurements available for all participants, specific eGFR measurements rather than estimates, and kidney biopsy data. Additionally, data may have been missing because some affected family members did not participate in the study. The high racial heterogenicity also means that the data cannot be generalized to areas outside of the Netherlands.

According to the authors, the results could aid other researchers in developing future studies that should address the added value of risk stratification and the potential impact of looking at family data of patients with CKD.

Zhang J, Thio CHL, Gansevoort RT, Snieder H. Familial aggregation of CKD and heritability of kidney biomarkers in the general population: The Lifelines cohort study. 

 Published online December 22, 2020. doi: 10.1053/j.ajkd.2020.11.012

Articles

A population-based study from the Netherlands showed that individuals with had at least 1 direct relative affected with chronic kidney disease (CKD), suggesting that biomarkers for CKD can aid in detecting the early stages of the disease.



Family History, Genetics May Help to Predict, Detect Early-Stage CKD

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

A flow cytometric score (FCM-score) developed in 2012, which uses 4 parameters to distinguish low-grade 

 (MDS) from nonclonal cytopenias, is simple and practical for screening MDS patients, according to research 

published in the American Journal of Translational Research

To improve upon this method, researchers investigated a gating strategy and cluster of differentiation (CD) markers in FCM for MDS diagnosis. Compared with the original score, the new version (MFCM-Score) exhibited better accuracy, objectiveness, and clinical application. 

MDS, classified by the World Health Organization (WHO) as myeloid neoplasms, are a group of heterogeneous diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias, and dysplasia in 1 or more myeloid lineage cells in bone marrow, authors explained.

Although the WHO classifies MDS based on peripheral cytopenias and bone marrow dysplasia evaluations, in clinical practice, patients may be negative for these diagnostic markers yet still have MDS, warranting additional diagnostic measures for these patients.

As research has shown that flow cytometry is capable of diagnosing reactive and clonal proliferations of bone marrow hematopoietic cells, the method has been explored as a potential diagnostic tool for MDS. However, because flow cytometry is expensive and requires a large number of antibodies, it is untenable in developing countries. To overcome these issues, the FCM-score was developed in 2012.

In the current study researchers recruited participants from a single hospital in China. Based on their medical history, clinical characteristics, morphological changes, and response to treatment, patients were divided into cohorts with MDS (n = 54) and nonclonal cytopenias (non-MDS) (n = 40).

Clinical and demographic data, in addition to bone marrow samples, were collected. Under the original method for FCM-scoring, combinations of antibodies CD34, CD19, CD33, and CD45 are analyzed for the following parameters: myeloblast-related cluster size (myeloblast-related cells/all nucleated cells), B-progenitor-related cluster size (B-progenitor-related cells/all CD34+ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). Originally, a value of 1 is assigned to each parameter and MDS was diagnosed if a FCM-score was 2 or greater, authors explained.

The original FCM scoring also used low side scatter (SSC) and CD45 expression to separate B lymphocyte progenitor cells and myeloblasts. In contrast, researchers’ gating and CD strategy “used CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34+CD45dimm population.”

Using patients’ data, investigators compared the 2 scores (at the cutoff of 2) and analyzed the relationship between the MFCM-score and the Revised International Prognostic Scoring System (IPSS-R) for MDS.

Using the FCM-score, 49 of 54 MDS cases were diagnosed (sensitivity 90.7%); 7 false-positives (misdiagnosed) were found in non-MDS patients (specificity 82.5%); the agreement between clinical and FCM-score diagnosis was 87.2%; the positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 86.8%, respectively.

Using the MFCM-score, 52 of 54 MDS cases were correctly diagnosed (sensitivity 96.3%); there were 5 false-positives in the non-MDS cohort (specificity 87.5%); the agreement between clinical and FCM-score diagnosis was 92.6%; the PPV and NPV were 91.2% and 94.6%, respectively.

Chi-square tests showed that the diagnostic rates by MFCM-score and FCM-score were similar (

MFCM-score had a positive correlation with the IPSS-R prognosis classification for MDS (Spearman 

All parameters in the MFCM-score were positively correlated to the IPSS-R grades in MDS (

The relatively small sample size and short period of follow-up mark limitations to the study, and the MFCM-score should be validated in large, multicenter prospective studies, the authors wrote.

“We can follow up the treatment and survival of MDS patients to validate the clinical significance of the MFCM-score in the treatment and prognosis of patients,” the researchers concluded. “The MFCM-score covers not only the low-grade MDS, but also all MDS subtypes, and it also has prognostic value for survival and can be used for treatment tracking.”

Guo J, Wang H, Xiong S, et al. Simplified flow cytometry scoring for diagnosis and prognosis of myelodysplastic symptom. 

A flow cytometric score developed in 2012, which uses 4 parameters to distinguish low-grade myelodysplastic syndromes (MDS) from nonclonal cytopenias, is simple and practical for screening patients with MDS, according to research published in the American Journal of Translational Research. 

Researchers Develop Improved Flow Cytometric Score for MDS Diagnosis

Tyrosine kinase inhibitor (TKI) therapy enables patients with chronic myeloid 

 (CML) to reach life expectancies equivalent to the general population and treatment-free remission (TFR), but QOL can deteriorate with treatment. A recent review set out to uncover factors likely to keep patients in TFR following TKI discontinuation, and 

 appeared in World Journal of Clinical Oncology.

With long-term TKI treatment having such serious adverse effects (AEs) as neutropenia, thrombocytopenia, anemia, hepatic toxicity, cerebrovascular arterial events, and pleural effusion, the investigators also wanted to be able to better predict which patients could safely discontinue treatment after achieving TFR.

, long-term (4-plus years) treatment with TKIs, and duration and depth of molecular response (MR) influence the likelihood of ongoing TFR, according to data from the TWISTER, STIM1, and EURO-SKI studies.

For example, in TWISTER, 51% of patients with a low SOKAL score achieved TFR. And in STIM1 and EURO-SKI, a higher likelihood of TFR was seen in patients on TKI therapy for more than 4.5 years and those who reached MR in at least 1 year and were on TKIs for longer than 5.8 years, respectively. In addition, results from the STAT2 trial out of Japan show a significantly higher rate of TFR with 3-year TKI use among patients with undetectable molecular residual disease compared with those without: 76.6% vs 48.6%.

To be able to safely discontinue treatment, better selection of patients likely to have ongoing survival is vital. For that, consensus on the clinical criteria patients should meet is necessary, the authors stated. However, at present, “there is still no European or international consensus regarding what criteria are important for selecting patients for a discontinuation attempt,” they noted.

They believe biomarkers for patients who achieve TFR vs those with disease relapse could better predict successful discontinuation of TKI treatment and ongoing remission, in addition to defining safer discontinuation attempts. Potential biomarkers include levels of natural killer cells and CD3+, CD8+, and CD62L+ T cells, based on study results showing TFR was more likely to continue the higher these cell levels.

“The identification of predictive factors for TFR in CML will inform the clinic on the best candidates to include in future discontinuation attempts and will help define criteria for safer discontinuation attempts with a greater probability of success,” the authors concluded. “Moreover, it would potentially give more patients a chance at stopping TKI treatment.”

They also highlight prospective cost savings from not having to treat ongoing AEs from TKI treatment, such as hepatic toxicity or cardiovascular comorbidities. At present, TKI treatment can reach well into 5 figures.

Areas to concentrate on going forward include determining the molecular factors associated with TFR, investigating the safety of a second discontinuation attempt if there is disease progression after a first attempt, and the patient perspective on QOL. This last factor is especially important, the authors note, because of the increased need for testing and molecular monitoring in the initial years of treatment stoppage.

Stuckey R, López-Ródriguez JF, Sánchez-Sosa S, et al. Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia. 

2020;11(12):996-1007. doi:10.5306/wjco.v11.i12.996

Tyrosine kinase inhibitor (TKI) therapy enables patients with chronic myeloid leukemia (CML) to reach life expectancies equivalent to the general population and treatment-free remission, but quality of life can deteriorate with treatment.


Likely Determinants of Successful TKI Treatment Stoppage Identified in CML

There is a greater prevalence of acid reflux disease in patients with both of these conditions, and treating the sleep apnea in turn may improve the acid reflux, which then may improve the cough, stated Krishna M. Sundar, MD, clinical professor, Pulmonary Division, Department of Medicine, and medical director, Sleep-Wake Center, University of Utah.

How are chronic cough and sleep apnea interrelated?

During sleep apnea, there's collapse of the upper airway. So there's constant closing and reopening of the upper airway. So there is a fair degree of upper airway trauma, which may cause damage to the nerve endings in the airway. These nerve endings may be important in sort of mediation or may be important in sort of leading to what we call neuropathic changes, which we now think form the basis of this chronic cough. So that's one explanation.

The other thing is that these patients tend to have more acid reflux disease. So if we treat the sleep apnea, that acid reflux gets better and that may improve the cough.

And thirdly, there may be also some effect of when somebody goes on CPAP [continuous positive airway pressure], the mask and machine at night, there is some degree of lung inflation, which may have direct effects on the cough.

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Dr Krishna Sundar: Airway Collapse, Upper Airway Trauma Contribute to the Co-occurrence of Chronic Cough, Sleep Apnea

A recent review highlighted different biologic therapies that are used or are being investigated for the treatment of several 

also discussed hypersensitivity reactions and as well as current research gaps that future investigators should address.

Biologics are used to treat a number of atopic and inflammatory conditions, including bronchial asthma, urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps (CRSwNP), hereditary angioedema, atopic dermatitis (AD), as well as rheumatoid arthritis and psoriatic arthritis. 

The authors, from German medical centers and universities, focused much of their review on omalizumab, which was first approved by EU regulators in 2005 as an add-on therapy for patients 12 years of age and older with severe persistent asthma. It was first approved in the United States in 2003 for allergic asthma; it is also approved for chronic urticaria and in December 2020 was approved by the FDA to treat CRSwNP.

Omalizumab has been shown to reduce the frequency of exacerbations and improve symptoms, quality of life, and lung function in patients with bronchial or severe allergic asthma. Compared with placebo, it has also demonstrated effectiveness in reducing nasal polyp scores, nasal obstruction and other symptoms of CRSwNP.

Other biologics for asthma include mepolizumab and reslizumab, which block interleukin 5 (IL-5); the IL-5 receptor benralizumab; and dupilumab, which inhibits the signaling of interleukin-4 and interleukin-13, 2 proteins that play a central role in type 2 inflammation.

Dupilumab is the only approved biologic for AD; it is approved for CRSwNP as well. The authors noted that it is considered a game-changer in AD as it is the only systemic therapy and that guidelines recommend limited use of corticosteroids.

The review also looked athereditary angioedema (HAE), a rare genetic condition that causes recurrent edema of the skin and mucous membranes occurs; its affects about 1 in 50,000 individuals. One biologic, lanadelumab, is available for long-term prevention of HAE in several markets, including Australia, Canada, those of the EU, Switzerland and the United States. It inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in HAE.

In CRSwNP, other biologics are in or have recently finished clinical trials could join omalizumab. They include mepolizumab, reslizumab, and benralizumab.

Omalizumab, mepolizumab, benralizumab, and dupilumab are approved for self-administration in the European Union and in the 

. Even if home administration is available, the researchers recommend seeing a physician for administration for at least 4 to 12 months to ensure that the patient doesn’t have any adverse reactions. 

The authors noted that anaphylactic reactions to biologics can occur even after months of use, and all biologics run the risk of cytokine release reactions, or type alpha reactions, as a result of an overstimulated immune response that are tied to the substance and dose. They are more frequent than unpredictable anaphylactic reactions and typically decrease if therapy continues.

The authors also briefly discussed what is known and unknown about biologic therapy in certain populations, namely, during pregnancy and in patients with unknown SARS-CoV-2 infection status.

In pregnancy, knowledge stems from what is known from the use of biologics in rheumatoid arthritis, lupus erythematosus, or psoriasis vulgaris. Older biologics, such as the use of anti-tumor necrosis factors infliximab, adalimumab, and etanercept, are recommended in pregnancy up to week 20. A newer biologic, certolizumab, has been shown to be safe for the entire pregnancy.

Guidelines are silent on omalizumab, although it was studied in a trial of pregnant women and was not shown to cause birth defects, the authors said. 

Other biologics either lack data or are not recommended; the authors suggested the use of register-based data or case-control studies for this population.

For the population of patients on biologic treatment concerned about infection with SARS-CoV-2, the authors cited a German position statement that therapy should continue, adding, "the therapy should be decided on individually together with the patient after a risk-benefit analysis in case of justified suspicion or proof of an infection with SARS-CoV-2."

Jappe U, Beckert H, Bergmann KC, et al. Biologics for atopic diseases: Indication, side effect management, and new developments. 

. Published online January 5, 2021. doi: 10.5414/ALX02197E

A recent review explores the use of biologics in atopic and inflammatory conditions as well as lingering research gaps.

 Review Examines Use of Biologics in Atopic, Inflammatory Diseases

 might benefit from aggressive treatment methods, a study recently published in 

 Although women aged 65 years and older are generally considered to have a worse prognosis than younger patients with epithelial ovarian cancer (EOC), there is not yet a consensus on the best way to treat them.

The study analyzed a group of 148 patients treated for EOC between 1998 and 2019 to assess outcomes in patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), an aggressive and complex treatment regimen. 

Researchers compared effects and outcomes around surgery by the type of treatment. Of the 148 patients identified, 42 underwent CRS plus HIPEC, 48 were treated with neoadjuvant chemotherapy plus CRS and HIPEC, and 58 underwent salvage CRS plus HIPEC. Age at the time of surgery (<65 years vs ≥65 years) was also taken into account.

At a median follow-up of 44.6 months, results showed that women treated with upfront CRS plus HIPEC had the longest median overall survival (OS) at 69.2 months for those younger than 65 years of age and 69.3 months for women 65 or older. In women who underwent neoadjuvant chemotherapy plus CRS and HIPEC, median OS was 26.9 months in the younger cohort and 32.9 months in the older group. Younger patients who were treated with salvage CRS plus HIPEC had a median OS of 45.6 months, compared with 23.9 months in the older cohort.

“Ovarian cancer frequently develops in older women. We often ask ourselves whether we should offer our older patients aggressive treatment modalities such as cytoreduction and HIPEC, whether the treatment is effective in these women and whether older women have more complications after these complex treatments,” study author Vadim Gushchin, MD, FACS, surgical oncologist and director of the HIPEC program at Institute for Cancer Care at Mercy in Baltimore, 

. “Our study suggests that the longevity of patients who underwent cytoreduction plus HIPEC for ovarian cancer was similar regardless of age, and older women were able to recover from this aggressive treatment well.”

Where progression-free survival (PFS) was concerned, the upfront CRS plus HIPEC showed a median of 43.3 months in the younger cohort and 45.4 months in the older cohort. PFS for younger patients given neoadjuvant chemotherapy plus CRS and HIPEC was 16.2 months vs. 11.2 months in the older cohort, and PFS in those treated with salvage cytoreductive surgery plus HIPEC was 18.7 months and 10 months, respectively.

“Caring for elderly patients requires additional skills and resources,” Gushchin said. “We will continue our efforts to quantify these requirements to make our results are applicable across other institutions. Also, we are planning to investigate how age factors together with molecular prognostic factors of ovarian cancer. These data could allow us to select patients better for different treatments.”

1. Zambrano-Vera K, Sardi A, Lopez-Ramirez F, et al. Outcomes for elderly ovarian cancer patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (crs/hipec). 

. Published online January 3, 2021. doi:10.1245/s10434-020-09415-4

2. Southall J. Older women with ovarian cancer may benefit from more aggressive treatment. Healio. January 14, 2021. Accessed January 15, 2021. https://www.healio.com/news/hematology-oncology/20210114/older-women-with-ovarian-cancer-may-benefit-from-more-aggressive-treatment

Certain elderly women with ovarian cancer might benefit from aggressive treatment methods, a study recently published in Annals of Surgical Oncology found.

Aggressive Treatment Might Benefit Older Patients With Ovarian Cancer 

Machine learning was shown to identify patients with 

 (RA) who present an increased chance of achieving clinical response with sarilumab, with those selected also showing an inferior response to adalimumab, according to 

 presented at ACR Convergence, the annual meeting of the 

In prior phase 3 trials comparing the interleukin 6 receptor (IL-6R) inhibitor sarilumab with placebo and the tumor necrosis factor α (TNF-α) inhibitor adalimumab, sarilumab appeared to provide superior efficacy for patients with moderate to severe RA. Although promising, the researchers of the abstract highlight that treatment of RA requires a more individualized approach to maximize efficacy and minimize risk of adverse events.

“The characteristics of patients who are most likely to benefit from sarilumab treatment remain poorly understood,” noted researchers.

Seeking to better identify the patients with RA who may best benefit from sarilumab treatment, the researchers applied machine learning to select from a predefined set of patient characteristics, which they hypothesized may help delineate the patients who could benefit most from either anti–IL-6R or anti–TNF-α treatment.

Following their extraction of data from the sarilumab clinical development program, the researchers utilized a decision tree classification approach to build predictive models on ACR response criteria at week 24 in patients from the phase 3 

 trial, focusing on the 200-mg dose of sarilumab. They incorporated the Generalized, Unbiased, Interaction Detection and Estimation (GUIDE) algorithm, including 17 categorical and 25 continuous baseline variables as candidate predictors. “These included protein biomarkers, disease activity scoring, and demographic data,” added the researchers.

Endpoints used were ACR20, ACR50, and ACR70 at week 24, with the resulting rule validated through application on independent data sets from the following trials:

MOBILITY (N = 1197; sarilumab [150 mg and 200 mg combined], n = 799; placebo, n = 398)

 (N = 546; sarilumab [150 mg and 200 mg combined], n = 365; placebo, n = 181)

 (N = 369; sarilumab, n = 184; adalimumab, n = 185)

 (N = 202; sarilumab [150 mg and 200 mg combined], n = 100; tocilizumab, 102)

Assessing the end points used, it was found that the most successful GUIDE model was trained against the ACR20 response. From the 42 candidate predictor variables, the combined presence of anticitrullinated protein antibodies (ACPA) and C-reactive protein >12.3 mg/L was identified as a predictor of better treatment outcomes with sarilumab, with those patients identified as rule-positive.

These rule-positive patients, which ranged from 34% to 51% in the sarilumab groups across the 4 trials, were shown to have more severe disease and poorer prognostic factors at baseline. They also exhibited better outcomes than rule-negative patients for most end points assessed, except for patients with inadequate response to TNF inhibitors.

Notably, rule-positive patients had a better response to sarilumab but an inferior response to adalimumab, except for patients of the HAQ-Disability Index minimal clinically important difference 

“If verified in prospective studies, this rule could facilitate treatment decision-making for patients with RA,” concluded the researchers.

Rehberg M, Giegerich C, Praestgaard A, et al. Identification of a rule to predict response to sarilumab in patients with rheumatoid arthritis using machine learning and clinical trial data. Presented at: ACR Convergence 2020; November 5-9, 2020. Accessed January 15, 2021. 021. Abstract 2006. https://acrabstracts.org/abstract/identification-of-a-rule-to-predict-response-to-sarilumab-in-patients-with-rheumatoid-arthritis-using-machine-learning-and-clinical-trial-data/

Machine learning identified patients with rheumatoid arthritis who may have an increased chance of achieving clinical response with sarilumab, with those selected also showing an inferior response to adalimumab.

Machine Learning Identifies Patient Response to Sarilumab in Rheumatoid Arthritis 

CMS finalized a new rule today that will allow certain payers, providers, and patients to have electronic access to pending and active prior authorization (PA) decisions.

The agency said the rule will streamline the PA process and allow providers to devote more time and focus to providing better quality care to patients. Promoting secure electronic access to data in new ways will drive interoperability, empower patients, and reduce costs and the burden on the health care system, CMS reiterated.

“Thanks to this rule, millions of patients will no longer have to wrangle with prior providers or locate ancient fax machines to take possession of their own data. Many providers, too, will be freed from the burden of piecing together patients’ health histories based on incomplete, half-forgotten snippets of information supplied by the patients themselves, as well as the most onerous elements of prior authorization,” said CMS Administrator Seema Verma 

Payers require PAs for oversight and control over provider prescribing patterns. In March 2020, the American College of Rheumatology 

 on CMS to improve the PA process and gave recommendations on how to do so, including adopting a national electronic standard for PAs and improving transparency on formulary decisions.

The CMS Interoperability and Prior Authorization rule will require Medicaid, Children’s Health Insurance Program managed care plans, fee-for-service programs, and issuers of individual market Qualified Health Plans on the federally facilitated exchanges to implement application programming interfaces (APIs). Doing so will enable providers to access data through integration with their electronic health records.

“By exchanging relevant health information between patients, providers, and payers, APIs support a better health care experience for patients. Patients have easier access to their own health information, their providers have a more complete picture of their care, and patients can take their information with them as they move from plan to plan, and from provider to provider throughout the healthcare system,” said the agency in the statement. “This ensures more coordinated, quality care, and less repetitive and unnecessary care that is costly.”

Payers regulated under the rule will be required to include claims and encounter data, including laboratory results and information regarding any pending and active PA decisions, into an API. The data should be directly shared with providers, when requested, and other payers in order to aid patients as they move between or among payers.

“In this way, patients, providers, and payers have the data when and where they need it, to help ensure that patients receive the best possible care,” said the agency.

The final rule will also require payers to reduce their decision timelines for PAs. In 2017, the American Medical Association 

 that 64% of providers have waited at least 1 business day for a PA from their health plan and 30%, at least 3 business days. Eighty-six percent also said the PA burden has increased over the last 5 years.

Payers will now have a maximum of 72 hours to make a decision on a PA application for urgent requests and 7 calendar days for nonurgent requests. If an application is denied, payers will have to provide a specific reason why, thereby increasing transparency for providers. To promote accountability, the rule will also require payers to make PA metrics public that detail how they operationalize the process.

CMS said that enabling patients to review the status of a PA application will provide them with a better experience, because they can better understand the timeline for the process and in turn be more able to plan next steps with their provider.

As the rule currently stands, Medicare Advantage plans are not included. However, CMS said that it is considering whether to include these plans in future rulemaking.

“This change will reverberate around the healthcare system for years and decades to come,” said Verma.

CMS puts patients over paperwork with new rule that addresses the prior authorization process. News release. CMS. January 15, 2021. Accessed January 15, 2021. https://www.cms.gov/newsroom/press-releases/cms-puts-patients-over-paperwork-new-rule-addresses-prior-authorization-process

CMS finalized a rule on electronic data entry that will streamline the prior authorization process and improve data transparency for providers, payers, and patients.

CMS Finalizes Rule on Electronic Prior Authorization

Luis Carrascosa, MD, a radiation oncologist at the Florida Cancer Specialists (FSA) Ocala Cancer Center, discusses new and upcoming trends in radiation therapy for prostate cancer.  

FCS works to stay at the forefront as new therapies are developed and approved. Are there any new or developing treatments in radiotherapy that you foresee improving patient outcomes and/or saving on costs?

There's a trend in radiation oncology treatments not only for prostate, but in a lot of other areas—lung cancer, breast cancer, and many other sites—in which we are now reducing the number of treatments. So we are doing stereotactic techniques, which give very high doses of radiation to a very small, precise area. That's definitely one of the ways that radiation is changing.

Other things that are coming along are, for example, all of our radiation treatment delivery is based on CT scan planning, and that’s a very good way of doing it. But there are some newer radiation machines that are having an MRI-based planning, so you're doing an MRI at the same time that you're doing the radiation. That's definitely something that is going to be very important in the future.

We're also looking at incorporating different tests. Recently, there are some newer agents for prostate cancer, specifically PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scanning, which has been 

 but is still not commercially available. But we're moving in the direction of better imaging techniques and things that are going to potentially improve the way that we individualize radiation and how we give radiation to patients. There's a lot of exciting things coming.

Another recent development in prostate cancer treatment just this year has been approval of PARP inhibitors for certain prostate cancer types. Do you see potential for utilizing targeted therapies in combination with radiation therapy as you look forward?

PARP inhibitors have been used in other types of cancers—for example, ovarian cancer—in which there are certain genetic changes, and so the same thought process has been applied to prostate cancer, and there's certain PARP inhibitors that are being utilized. For prostate cancer in some scenarios, we're entering into an era in which we are exploring how all these new agents are going to combine with radiation. We see a lot of potential for some of these targeted therapies or immunotherapy, and how to incorporate all of these newer agents with radiation. We think there's really good potential that we could improve outcomes with those combinations. Trials are going on, but there's a lot of potential.

Luis Carrascosa, MD, a radiation oncologist at the Florida Cancer Specialists Ocala Cancer Center, discusses new and upcoming trends in radiation therapy for prostate cancer.  

Dr Luis Carrascosa on Innovations in Radiation Therapy for Prostate Cancer

underscores the substantial economic burden associated with early discontinuation of guideline-recommended hypomethylating agent (HMA) therapy among patients with refractory anemia with excess blasts (RAEB), a diagnosis that substantially overlaps with higher-risk 

HMAs are recommended therapeutic options for patients with HR-MDS because they have been associated with survival benefit, improved quality of life, and improvement in cytopenias, which leads to delayed progression to acute myeloid 

“In order to elicit clinical response, HMA treatment is recommended to be provided to patients for least 4, or even 6, treatment cycles,” the authors wrote, while “premature treatment discontinuation or suboptimal treatment is likely to affect clinical and economic outcome.”

However, difficulties ensuring treatment cycles are administered as scheduled have been reported, with one study finding a reported delay in 31% of scheduled cycles among patients with MDS and other hematologic disorders.

To estimate and compare the economic impact of HMA nonpersistence in patients with HR-MDS who received the treatment, researchers conducted a retrospective observational cohort analysis. Patient data, recorded between 2010 and 2016, were gleaned from the Surveillance, Epidemiology, and End Results (SEER)-Medicine linked database.

Within the data set, demographic and clinical characteristics, regional cancer registry data, and information on cause of death for those with cancer are linked to Medicare claims.

All individuals included in the analysis were diagnosed with MDS and subsequently initiated HMA treatment. As RAEB is a histologic designation that often overlaps with HR-MDS, the International Prognostic Scoring System (IPSS) code for RAEB was used to determine diagnoses.

In addition, “Patients were required to be ≥ 66 years of age at diagnosis and continuously enrolled in Medicare Parts A and B for ≥ 12 months before initial MDS diagnosis until the end of the study period, which was defined as censoring, death, or December 31, 2016, whichever occurred first.” Patients’ health care resource use (HCRU) was also assessed, and associated costs were calculated as per patient per month (PPPM), inflated to 2018 US$.

A total of 664 patients were included in the final analysis, of whom 369 (55.6%) were persistent with HMAs and 295 (44.4%) were nonpersistent—defined as receiving fewer than 4 cycles of HMA treatment or having a gap (≥90 days) in cycles.

A weighted generalized linear model (GLM) analysis found “the HMA non-persistent group incurred significantly (

 < .05) higher total PPPM costs compared to the HMA-persistent group ($18,039 vs $13,893), particularly for hospitalization ($3375 vs $2131), and emergency room ($5517 vs $2867) costs.”

An inverse probability of treatment weight–weighted regression analysis also showed PPPM resource utilization was significantly higher among HMA-nonpersistent patients for hospitalizations, emergency use visits, and receipt of care via home health, hospice, or skilled nursing facility compared with persistent patients. However, the rate of outpatient and physician visits was significantly higher among HMA-persistent patients.

Investigators also found “sensitivity analysis among patients who were alive for ≥ 4 months suggested that HMA-non-persistent patients had higher utilization rate for emergency room visits, hospitalizations, home health, hospice care, and skilled nursing facility.”

Among nonpersistent patients, there was a significantly higher proportion of older patients and individuals without a partner compared with the HMA-persistent group. According to researchers, this finding suggests these patient subgroups may need support to continue with their treatment cycles.

The data used in the study did not include reasons for HMA treatment discontinuation, marking a limitation. Authors also cautioned findings may not be generalizable as only those 66 years and older were included in the study.

“The high proportion of patients in the HMA-non-persistent group warrants closer care management to achieve better outcomes and reduced healthcare spending,” they concluded.

Joshi N, Kale H, Corman S, Wert T, Hill K, Zeidan AM. Direct medical costs associated with treatment non-persistence in patients with higher-risk myelodysplastic syndromes receiving hypomethylating agents: a large retrospective cohort analysis. 

 Published online December 8, 2020. doi:10.1016/j.clml.2020.12.002

New research underscores the substantial economic burden associated with early discontinuation of guideline-recommended hypomethylating agent (HMA) therapy among patients with refractory anemia with excess blasts, a diagnosis that substantially overlaps with higher-risk myelodysplastic syndrome (MDS).

Analysis Reveals High Cost of Discontinued HMA Treatment for MDS

Mepolizumab and benralizumab are both potent targets of the interlukin-5 (IL-5) pathway with the ability to significantly reduce eosinophil counts, according to new 

 Although no statistical difference in the magnitude of eosinophil reduction offered by each agent was found, researchers noted “benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.”

, is a helper T cell 2 (Th2)–mediated process characterized by high blood and sputum eosinophil count. Canadian patients with eosinophilic asthma can currently choose from 4 targeted monoclonal antibodies approved by Health Canada, including mepolizumab and reslizumab, which target IL-5, and benralizumab, which targets the IL-5 receptor alpha (IL-5Rα) subunit.

“All IL-5 therapies have been shown to reduce oral corticosteroid use and overall asthma exacerbations,” the authors explained. But because benralizumab has a unique ability to deplete eosinophils compared with direct IL-5 antibodies, it is unclear whether it has clinical superiority.

Specifically, benralizumab acts by binding to the IL-5Rα subunit on eosinophils, which “not only prevents signal transduction but also triggers cell-mediated killing by the innate immune system resulting in eosinophil depletion.”

Because of its role in eosinophil activation, maturation, and survival, IL-5 has been a focus of treatment research for severe eosinophilic asthma for years. However, “Current Global Initiative for Asthma clinical guidelines released in 2019 do not provide guidance on selecting the various IL-5 treatment options.”

To determine if the peripheral eosinophil reduction efficacy of mepolizumab and benralizumab differ, researchers conducted a retrospective chart review of Canadian patients with severe eosinophilic asthma who were approved for either treatment.

All participants presented to a single center in Kitchener, Ontario, and any patients with noted nonadherence or who were on fluctuating doses of corticosteroids for non–asthma-related illness were excluded from the review.

Investigators compared pretreatment baseline eosinophil counts with posttreatment counts, defined as the highest count recorded after therapy start date with at least 30 days of adherence.

Over the course of the study window, 5 participants switched from mepolizumab to benralizumab due to inadequate control of asthma or intolerance to the therapy, whereas no participants switched from benralizumab to mepolizumab.

A total of 36 patients taking mepolizumab and 19 patients taking benralizumab were included in final analyses. No statistically significant differences between age, sex, smoking history, mean number of comorbidities, or additional compounding factors were found.

The mean pretherapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/mcL) compared with benralizumab (521.6 cells/mcL) (

The percentage of patients with eosinophilia (≥ 500 cells/mcL) prior to therapy onset was similar between groups (

Both therapies resulted in a significant decrease in eosinophil count (

 < .0001) but the mean decrease did not statistically differ between patients taking mepolizumab and those taking benralizumab (

All patients with eosinophilia prior to therapy onset had posttherapy eosinophil counts within normal limits (< 500 cells/mcL).

100% of patients receiving benralizumab had undetectable eosinophil counts post therapy compared with 31% of patients receiving mepolizumab (

Two patients in the mepolizumab group exhibited elevations in their serum eosinophil count post therapy, with counts increasing from 200/cells mcL to 300 cells/mcL.

A small sample size and selection bias mark limitations to this study, and the retrospective nature of the study precludes understanding differences in potential confounders that were not measured.

In addition, “correlation of eosinophil depletion with clinical outcomes, such as measures of asthma control, effect on asthma exacerbation rates, changes in [forced expiratory volume in 1 second], or other biomarkers of asthma control—such as sputum eosinophil count or fractional exhaled nitric oxide—was not possible as the timing of the measurement of these clinical outcomes post-therapy onset was highly variable between patients, if these measurements were even available,” researchers noted.

Future studies ought to further evaluate the clinical significance of the noted difference found in this study, they concluded.

Ghassemian A, Park JJ, Tsoulis MW, and Kim H. Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts. 

Published online January 6, 2021. doi:10.1186/s13223-020-00507-0

Mepolizumab and benralizumab are both potent targets of the interlukin-5 pathway with the ability to significantly reduce eosinophil counts, according to new research published in Allergy, Asthma & Clinical Immunology. 