Tricia Krizner

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“Biologics are innovative treatment options for patients affected by debilitating and life-threatening diseases; however, they are often associated with high costs and limited patient access. Fortunately, more affordable options for many patients who rely on biologic treatments are beginning to enter the market: biosimilars,” reads an excerpt from, Why Biosimilars Are Important for Patients, published in February 2018 by the Biosimilars Council, a division of the Association for Accessible Medicines. “The launch of new biosimilars over the next decade could save consumers as much as $250 billion and boost access to biologic treatments for an additional 1.2 million patients by 2025,” according to the article.

U.S. drug spend and utilization for biosimilars has steadily increased year after year, says 

® Editorial Advisor David Calabrese, RPh, MHP, senior vice president and chief pharmacy officer, OptumRx.

From 2017 to 2018, spending grew from $46 billion to $54.1 billion.

For this review, Calabrese provides information for products that have not had a previous biosimilar launch. The top five drugs that have biosimilars in the pipeline, he says, are: Humira, Enbrel, Lucentis, Actemra, and Eylea.

. Humira is prescribed to treat rheumatoid arthritis, chronic plaque psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis, and non-infectious uveitis.

“Humira has been the number one selling drug for many years, and its costs has risen dramatically over the years, about $19,000 a year in 2012 to more than $38,000 today,” Calabrese says.

3 Ways Insurers Can Help Promote Biosimilar Adoption


	
	Five biosimilars for Humira have been FDA approved within the past three years. The first to receive approval, in 2016, was 

) for the treatment of seven inflammatory diseases. 

 was approved next, in 2017, followed by 

, which was approved in 2018. In July 2019 the FDA approved a fourth biosimilar, 

, for all eligible indications of the biologic product. And in November 2019, 

 was approved. All of these biosimilars are expected to launch in 2023. There are six more companies with biosimilars in phase 3 trials, according to Calabrese.

, a drug licensed in 1998, is prescribed for the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. Two biosimilars are coming to market: the first, approved in August 2016, is Erelzi (etanercept-szzs). The second, Eticovo (etanercept-ykro), was approved in April 2019. Both drugs have a launch date of 2H 2020 or possibly 2029. Patent litigation is ongoing and 2029 appears to be the more likely launch date, however there is still a small chance that court judgment could favor the biosimilar manufacturer enabling a 2020 launch, Calabrese says. There are two more companies with biosimilars in phase 3 trials.

 will have three biosimilars on the market, all currently in phase 3 trials: FYB201, Xlucane, and SB11. Lucentis is used to treat wet age-related macular degeneration; diabetic macular edema; macular edema following retinal vein occlusion; diabetic retinopathy; and myopic choroidal neovascularization.

 is used alone or with other medications to treat moderate to severe rheumatoid arthritis, which affects about 1.3 million U.S. adults. In addition to rheumatoid arthritis, tocilizumab is also indicated to treat giant cell arteritis in adult patients, polyarticular juvenile idiopathic arthritis, and juvenile idiopathic arthritis. BAT1806 is a biosimilar in phase 3 trials. The manufacturer plans to file for approval in 2021, with a release date of July 2022 or later.

is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of wet age-related macular degeneration; diabetic macular edema; macular edema following retinal vein occlusion; diabetic retinopathy. The biosimilar MYL-1701P, is in phase 3 trials, with plans to file in the first quarter of 2021, with a release date of 2023.

Tricia Krizner is a Cleveland-based writer.

Articles

Several biosimilars will come to market within the next few years.

Biosimilars in the Pipeline

Cincinnati Children’s Hospital Medical Center

 has called Avondale, Ohio, home since 1926. The hospital has been on a decades-long mission to lead, advocate, and collaborate in order to improve the health of local children and reduce health disparities in targeted populations.

Two such population groups were the focus of a health initiative aimed at reducing the inpatient bed-day rate by at least 10% by mid-2020 for children from two nearby neighborhoods, and to narrow the gap between those neighborhoods and healthier ones.

“This was not a simple or straightforward program,” says the initiative’s lead researcher Andrew F. Beck, MD, attending physician, Division of General & Community Pediatrics and Division of Hospital Medicine at the health system. “Rather, it was complex, involving active collaboration with community partners.”

Beck and fellow researchers explored common elements that underpin morbidity across conditions and serve as key contributors to hospital days and disparities. This focus allowed them to bring the right hospital resources and community partners to the table to tackle the most problematic conditions.

The multi-level approach involved analyzing real-time EHRs to identify neighborhood “hot spots” in need of additional support for children living within those neighborhoods; optimizing chronic disease management by closing care gaps during hospitalizations and after discharge; mitigating social risks such as housing instability and limited access to medications and personal hygiene supplies; and helping children transition out of the hospital. The researchers hoped to develop, test, and refine a theory for how to narrow equity gaps across broader geographic areas.

There were exact improvements within each of these domains.  First, we engineered the EHR to send us alerts every morning if any child from the target neighborhoods was admitted.  This prompted a multi-disciplinary huddle for learning purposes to explore what could have prevented, care gap closure to look into preventive solutions during the hospitalization, like immunizations, and consideration of transition needs (e.g., follow up appointments, medications).  Second, we placed focus on common chronic conditions that were disproportionately contributing to bed-days.  For instance, we have pursued work with our asthma patients to ensure that they have controller medications prior to exacerbation seasons.  We also looked at the distribution of RN and social work care managers to ensure that they were connected with our most at-risk patients.  Third, we have worked with community partners to assess for patterns in social risks.  For instance, we have actively sought to identify building complexes that need broader advocacy and not just patient-level work.  When we identified resource limitations, we actively worked with the local food bank to start an in-clinic food pantry to deliver food into the neighborhood and bolster access to hygiene supplies.

Societal factors influence health outcomes


	In many neighborhoods like Avondale and Price Hill, access to pharmacies, grocery stores, green spaces, and adequate transportation can be limited. Housing may have exposures known to adversely affect health (e.g., pests, mold). This constellation of social, economic, and environmental factors influences short- and long-term health outcomes at the patient level, researchers say.

“We manage about 95% of all pediatric hospitalizations for children living in the county and nearly 100% of children in those neighborhoods,” Beck says. “Child hospitalization rates are high in those neighborhoods and are likely driven by a combination of social, economic, and environmental factors, so we set out to foster healthier communities where it was most urgently needed.”

The Impact of Care Coordination on Caregivers

Beck and his team defined a goal in spring 2015: to reduce the inpatient bed-day rate for children from Avondale and Price Hill by at least 10% by June 30, 2020. Meeting this goal required being accountable for an entire population and focusing on the root causes of place-based inequities, he says.

Improvement efforts began in July of that year, with the assembly of a multidisciplinary team that included inpatient and outpatient medical providers, social workers, community partners (such as legal aid), and parents of neighborhood children.

This initiative focused on roughly 8,000 children living in the high-morbidity, high-poverty Avondale and Price Hill neighborhoods. Children from these communities disproportionately experienced morbidity across nearly every condition and pediatric subspecialty.

The study period was between July 2012 and June 2018, with July 2012–June 2015 as the baseline phase and July 2015–June 2018 as the improvement phase.

Across the entirety of the study period there were a total of 38,583 hospitalizations for in-county children, of which 37,337 (97%) lasted less than 14 days. Hospitalizations that met diagnostic and length-of-stay inclusion criteria contributed 76,759 inpatient bed-days. The county’s inpatient bed-day rate was 5.6 days per 1,000 children per month.

The baseline rate for Avondale and Price Hill was 8.4 days per 1,000 children per month. This equated to neighborhood children collectively spending about 75 days each month and 900 days each year on inpatient units in Cincinnati Children’s Hospital Medical Center before improvement efforts began in the summer of 2015.

By the end of the study period in 2018, the average monthly inpatient bed-day rate decreased to 6.9 per 1,000 children, or 18% fewer in-hospital days than at baseline (July 2012–June 2015). There was no similar decrease in the rate for control neighborhoods, . where the rate remained at 7.6 inpatient bed-days per 1,000 children per month throughout the study period.

The rate reduction in Avondale and Price Hill was likely driven by fewer hospitalizations instead of shorter lengths-of-stay. The hospitalization rate dropped 20%-from 4.1 events per 1,000 children per month to 3.3 events-again beginning during the summer of 2015.

Finally, researchers assessed the degree to which the efforts narrowed equity gaps relative to the rest of the county. For the baseline period, Avondale had the fourth-highest and Price Hill the 11th-highest inpatient bed-day rates out of 80 county neighborhoods. In that period, Avondale and Price Hill children spent 2,720 days in the hospital, compared to 2,145 in the improvement period (July 2015–June 2018). The number of hospitalizations decreased from 1,344 to 1,041. Indicative of a move toward equity, Avondale improved to the ninth-highest and Price Hill to the 15-highest inpatient bed-day rates.


	Beck says he and his team have been encouraged by the marked, statistically significant improvements in Avondale and Price Hill when comparing two key metrics from the 2012-2015 benchmark to their results in 2015-2018: the inpatient bed-day rate and hospitalizations.

“This meant children spend hundreds of additional days at school and at home instead of in the hospital,” Beck says.

While they are pleased with the results, there is still progress to be made, Beck says. “We are taking what we have learned from our efforts in Avondale and Price Hill into account as we plan for scale and spread across additional local neighborhoods. We believe that the theories and methods used to decrease bed-day rates and hospitalizations could serve as a relevant example to other pediatric population health improvement projects-locally as well as nationally.”

 were recently published in Health Affairs.

How one hospital is combatting neighborhood-specific problems.

Population Health Initiative Reduces Pediatric Hospitalization Rate

	Mothers who breastfeed have a lower risk of developing breast cancer. That is one of the findings of a report of the American Institute of Cancer Research (AICR), which was released to mark World Breastfeeding Week in early August.

Diet, Nutrition, Physical Activity and Breast Cancer

, is a joint effort of AICR and the World Cancer Research Fund (WCRF), and is the result of systematic literature review on breast cancer. An independent panel of world-renowned experts evaluates and interprets the evidence and makes conclusions about what increases and decreases cancer risk.

	One area of study in the report is lactation. It identified and reviewed 18 studies on lactation, 13 of which focused on duration, showing a 2% decreased risk of breast cancer per five-month increase in breastfeeding. While the lower risk is modest, it is one additional reason to breastfeed for moms who are able, researchers say.

Bender"It isn’t always possible for moms to breastfeed but for those who can, know that breastfeeding can offer cancer protection for both the mother and the child,” says AICR’s Director of Nutrition Programs Alice Bender, MS, RDN.

	AICR recommends that new mothers breastfeed exclusively for up to six months and then add other liquids and foods. This advice is in line with recommendations of other health organizations, including the World Health Organization. Breastfeeding provides the nutrients babies need, helps protect them from infections and asthma, and boosts their immune system.

	There are several possible reasons that breastfeeding may influence breast cancer risk, according to the report. Lactation may delay a new mother’s menstrual periods, reducing lifetime exposure to hormones such as estrogen, which is linked to breast cancer risk. Also, the shedding of breast tissue after lactation may help rid cells with potential DNA damage.

	“With the many benefits of breastfeeding, it’s important that new moms get support to successfully breastfeed for longer than a few days or weeks,” Bender says. “I am a strong proponent that lactation, education and support should really be a normal part of pre- and postnatal care.”

	Breastfeeding provides health benefits now for the baby and later in life for both mom and baby, she adds.

	“It’s also critical to know there are steps all women can take to lower the risk of this cancer,” Bender says. “For women who don’t have children, have not breastfed or are choosing not to breastfeed, I think it’s important to emphasize that there are other lifestyle factors that can reduce breast cancer risk, and they include avoiding alcohol, being a healthy weight and physical activity.”

	The report finds that being overweight or obese in adulthood before menopause decreases the risk of premenopausal cancer. However, it increases the risk of postmenopausal breast cancer.

	Achieving and staying at a healthy weight can be difficult, and getting help to do it is even more challenging as nutrition counseling is sporadically covered by health insurance plans.

	“(Nutrition counseling) is often more therapeutic than for working with health behavior change,” Bender says. “So sometimes it’s covered in hospitals but not on an outpatient basis. We have 100,000 registered dieticians in this country all ready to help people make healthier diet changes,” she adds. “But oftentimes people do not have access to them because they don’t have insurance coverage for that kind of counseling and treatment.

	“I think with any kind of preventive care, especially lifestyle, the benefits come later in life. That is especially true with many types of adult-onset cancers like postmenopausal cancer,” Bender says. “For the healthcare insurance industry, the payoff in investment may not be seen until years later.”

There are several possible reasons that breastfeeding may influence breast cancer risk, according to the American Institute of Cancer Research. Find out what they are.

How does breastfeeding influence breast cancer risk?

	In the Ashkenazi Jewish population, the mutation profile of 

 is distinctive, with three ancient founder mutations in these two genes. Combined, these three mutations are responsible for 10% of invasive breast cancer among Ashkenazi Jewish women.

	The relatively high frequency of the Ashkenazi Jewish founder mutations in 

 has enabled the effective use of cancer genetics services by Jewish women, according to 

	For Ashkenazi Jewish patients with breast cancer who do 

 carry one of these three founder mutations, the chance of carrying some other pathogenic mutation in 

, or a pathogenic mutation in a different breast cancer gene, is not known. This information, however, would be valuable to patients and their families for cancer prevention and treatment.

	A group of researchers, led by Mary-Claire King, PhD, Department of Medicine, University of Washington in Seattle, conducted a study to determine the frequency of cancer-predisposing mutations other than the 

 founder mutations among patients of Ashkenazi Jewish ancestry with breast cancer.

	Should Ashkenazi Jewish women with breast or ovarian cancer who have negative results for the three founder mutations obtain complete sequencing of 

 so as not to miss some other mutation? Should these patients also be tested for mutations in other breast cancer genes?

	“We addressed these questions by sequencing all known breast and ovarian cancer genes in genomic DNA, which was provided by participants of the New York Breast Cancer Study (NYBCS), a longstanding cohort of Ashkenazi Jewish women with a primary diagnosis of invasive breast cancer,” the authors said.

	The result, they said, is that Ashkenazi Jewish patients with breast cancer can benefit from genetic testing for all breast cancer genes. Comprehensive sequencing would provide complete relevant genetic information.

	In the study, genomic DNA of women from 12 major cancer centers with a first diagnosis of invasive breast cancer who identified themselves and all four grandparents as Ashkenazi Jewish and participated from 1996 to 2000 was sequenced for 23 known and candidate breast cancer genes. Data analysis was performed from July 10, 2014, to March 10, 2017.

	Of the 1,007 patients in the study, 903 had no founder mutations in 

; of those 903 patients, 7 (0.8%) carried another pathogenic mutation in 

, and 31 (3.4%) carried a pathogenic mutation in another breast cancer gene.

	Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a 

 founder mutation, 4.9% (7 of 142) to another 

 mutation, and 21.8% (31 of 142) to a mutation in another gene. Overall, 14.1% (142 of 1,007) of Ashkenazi Jewish patients with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (111 of 1,007) in 

, and 3.1% (341 of 1,007) in another breast cancer gene. Of the 111 patients with 

 mutations, 57 (51.4%) had a mother or sister with breast or ovarian cancer and 54 patients (48.6%) did not.

	The authors concluded that, “The most recent national screening guidelines recommend genetic testing for all Ashkenazi Jewish patients with breast cancer. This recommendation is fine, but testing women only after they develop cancer severely limits the power of precision medicine.

	“To discover a mutation only after cancer is diagnosed is a missed opportunity to have prevented that cancer,” the authors added. “Many of these cancers could be prevented by offering genetic testing as described here to all women before they develop breast cancer, as part of routine medical care.”

New research shows that these certain patients with breast cancer can benefit from genetic testing for all breast cancer genes. 

Genetic testing may benefit this population

 found that women who take low-dose or baby aspirin at least three times a week have a 20% lower risk of developing HR-positive/HER2-negative breast cancer, which is the most common breast cancer subtype. This is the finding of a study published online May 1 in 

	The study assessed the potential risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in female public school professionals in California.

	The team of researchers chose to focus on low-dose aspirin, because not only is it inexpensive and readily available as a potential means of prevention, but because there are a lot of people already taking it for prevention of other diseases such as heart disease and colon cancer.

, the study used data from more than 57,000 women who were part of the 

 (CTS) and is the first to suggest that the reduction in risk is associated with low-dose aspirin.

	Bernstein, professor and director of the Division of Biomarkers of Early Detection and Prevention at City of Hope, an independent research and treatment center in Duarte, Calif., says that one reason for the finding may be that aspirin can lower inflammation.

	“Simple things like obesity or inflammatory conditions are a risk factor for breast cancer, so this may be one reason it could help," she says.

	Bernstein and her colleagues saw an overall 16% lower risk of breast cancer in women who reported using low-dose aspirin at least three times per week. Such regular use of low-dose aspirin reduced the risk by 20% of estrogen or progesterone receptor positive, HER2 negative breast cancer.

	“The study found an interesting protective association between low-dose aspirin and breast cancer,” according to lead author Christina A. Clarke, PhD, MPH, from the Cancer Prevention Institute of California. “We did not, by and large, find associations with other pain medications like ibuprofen and acetaminophen. We also did not find associations with regular aspirin since this type of medication is taken sporadically for headaches or other pain, and not daily for prevention of cardiovascular disease.”

	The CTS cohort was established in 1995 to 1996 when 133,479 active and retired female teachers, administrators and other public school professionals were recruited through the California State Teachers Retirement System. Participants completed a baseline questionnaire that collected information on family history of cancer and other conditions, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol and tobacco use, physical activity history, and frequency and duration of prior use of certain medications, including aspirin (but without detail on aspirin dose).

	In 2005 to 2006, 57,164 participants completed a 10-year follow-up questionnaire, which collected updated information on frequency of current use of aspirin, low-dose aspirin and other pain-relieving medications, weight, alcohol use, menopausal status, use of hormone therapy (HT), and physical activity. In the ensuing years through 2012, 1,457 of these participants developed invasive breast cancer.

	CTS participants are followed annually for changes of address, cancer diagnoses, hospitalizations, outpatient surgeries, emergency room visits and death. The CTS is overseen by the Institutional Review Boards of the Cancer Prevention Institute of California, the California Health and Human Services Agency, the University of California, Irvine, the University of Southern California, and the City of Hope.

	Now that there is some data separating low-dose from higher-dose aspirin, more detailed research can be undertaken to understand the full value of low-dose aspirin for breast cancer prevention, Clarke says.

Since the writing of this study, Clarke has taken a position at GRAIL, Inc., Menlo Park, Calif.

The medication’s ability to reduce inflammation sited as one possible explanation.

Regular use of low-dose aspirin may lower breast cancer risk

	The number of women in the United States living with distant metastatic breast cancer (MBC) is growing, likely because of an aging population and improvements in treatment, according to a study published online in 

Cancer Epidemiology, Biomarkers & Prevention

	Researchers came to this finding by estimating the number of U.S. women living with MBC, or breast cancer that has spread to distant sites in the body, including women who were initially diagnosed with metastatic disease, and those who developed MBC after an initial diagnosis at an earlier stage. Researchers also found that median and five-year relative survival for women initially diagnosed with MBC is improving, especially among younger women.

	The increasing burden of MBC highlights the importance of documenting recurrence to foster more research into the specific needs of this understudied population, researchers report.

	The study was led by Angela Mariotto, PhD, chief of the Data Analytics Branch of the Division of Cancer Control and Population Sciences at the National Cancer Institute (NCI), with coauthors from NCI, the Metastatic Breast Cancer Alliance, and the Fred Hutchinson Cancer Research Center.

	“Even though this group of patients with MBC is increasing in size, our findings are favorable,” Mariotto says. “This is because, over time, these women are living longer with MBC. Longer survival with MBC means increased needs for services and research. Our study helps to document this need.”

	The study uses population-based data to estimate the prevalence of MBC. Although researchers have been able to estimate the number of women initially diagnosed with MBC, data on the number of women whose cancers spread to a distant organ site, either as a progression or recurrence after being first diagnosed with an earlier stage of breast cancer, has been lacking because U.S. registries do not routinely collect or report data on recurrence.

	To develop a more accurate estimate of the total number of women living with MBC, researchers used data from NCI’s Surveillance, Epidemiology, and End Results (SEER) Program to include women who developed MBC after diagnosis. The researchers estimated that, as of Jan. 1, 2017, more than 150,000 women in this country were living with MBC, and that three out of four of them had initially been diagnosed with an earlier stage of breast cancer.

	The study shows that despite the poor prognosis of MBC, survival of women initially diagnosed with MBC has been increasing, especially among women diagnosed at younger ages. Researchers estimate a twofold increase in five-year relative survival rate from 18% to 36%, for women initially diagnosed with MBC at age 15 to 49 years between 1992 to 1994 and 2005 to 2012, respectively. The researchers also reported that a small but meaningful number of women live many years after an initial diagnosis of MBC. More than 11% of women diagnosed between 2000 to 2004 under the age of 64 survived 10 years or more.

	Based on their calculations, the researchers project that the number of women living with MBC will increase by 31% from 2010 to 2020.

	Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations. To help implement the comprehensive and accurate collection of these data, NCI is funding pilot studies aimed at identifying ways to leverage existing data and informatics methods to efficiently capture information on recurrent disease.

	By including women with recurrence, this study provides a more accurate number of women in the U.S. currently living with MBC. This estimation can help with healthcare planning and the ultimate goal of better serving these women, researchers conclude.

Study highlights the need for services and research for this understudied population.