News Connection- December 2015

RESOURCES: Interleukin-6 Plays Pivotal Role in Pathophysiology of RA

Rheumatoid arthritis (RA), estimated to affect at least 1.3 million Americans, is a chronic systemic disease resulting in pain, stiffness, swell-ing, and function of joints.¹ Interleukin-6 (IL-6), a multifunctional cytokine, plays an important part in the pathophysiology of rheumatoid arthritis (RA) and is a critical node in the inflammatory cytokine network.^2-5

In order for there to be balance within the inflammatory process, there must be normal levels of cytokines and other signaling molecules.  Elevated levels of IL-6 can disrupt balance and add to chronic inflammation and disease progression in conditions of autoimmunity and chronic inflam-mation.²

In response to severe infections, some studies have shown that serum IL-6 levels may reach 10,000 pg/mL. In healthy subjects, serum levels of circulating IL-6 range from ~1 pg/mL to ~16 pg/mL, but in patients with RA, serum IL-6 levels range from 5 pg/mL to 200 pg/mL, with 100- to 1000-fold higher concentrations found in synovial fluid.^2,3

IL-6 is one of the most abundant cytokines in the serum and synovial fluid of the inflamed joints of patients with RA and is associated with disease activity and articular destruction.²

IL-6 levels that remain high for an extended period of time, may have an affect on multiple physiologic processes including metabolism (lipid, glucose), hematopoiesis, the central nervous system, and host defense.^1,7-9 Elevated levels of IL-6 in patients with RA have been associated with disease activity, articular destruction, and systemic manifestations. It may also contribute to fatigue, anemia, osteoporosis, and cardiovascular disease.²

1. Ruderman E, Tambar S. Rheumatoid arthritis. Amer-ican College of Rheumatology website. Updated August 2012. Accessed May 8, 2015.
2. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford). 2010;49(1):15-24.
3. Choy E. Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v3-v11.
4. Liang KP, Myasoedova E, Crowson CS, et al. Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis. 2010;69(9):1665-1670.
5. Rho YH, Chung CP, Oeser A, et al. Inflammatory mediators and premature coronary atheroscle-rosis in rheumatoid arthritis. Arthritis Rheum. 2009;61(11)1580-1585.
6. Desgeorges A, Gabay C, Silacci P, et al. Concentra-tions and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid. J Rheumatol. 1997;24(8):1510-1516.
7. Saxena A, Cronstein BN. Acute phase reactants and the concept of inflammation. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, eds. Kelley’s Textbook of Rheumatology. Vol 1. 9th ed. Philadelphia, PA: Elsevier/Saunders; 2013:818-829.
8. Tutuncu Z, Kavanaugh A. Anticytokine therapies. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, eds. Kelley’s Textbook of Rheumatology. Vol 1. 9th ed. Philadelphia, PA: Elsevier/Saunders; 2013:957-977.
9. Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8(9):1227-1236.

SBM Recommends Insurers Expand Coverage of Diabetes Self-management Resources

The Society of Behavioral Medicine (SBM) announced policy guidance that suggested Medicare, Medicaid, and private insurers expand coverage of diabetes self-management (DSM) education and resources [Transl Behav Med. 2015;5(3):354-356]. Their recommendations come after multiple studies concluded that DSM education and support improves a patient’s management of diabetes and reduces complications, health care costs, and hospitalizations. Only 30% to 40% of diabetes patients receive DSM education and support, and a survey found that of 10 state Medicaid plans and 40 private insurance plans, only half covered DSM education and support. The authors of the SBM guidance indicated 3 limitations to access to current DSM resources: (1) restricted insurance coverage; (2) cost; and (3) patients required to have health care provider certification to prove they have diabetes prior to receiving DSM education.

Current policy states Medicare will reimburse for 10 hours of DSM education and 3 hours of medical nutrition therapy on 3 occasions: (1) it is within the first year following a diabetes diagnosis; (2) a diabetes drug new to the patient is started; or (3) the patient has a physician-written certification that he or she is at high-risk for complications. If none of these instances apply, Medicare will only cover 2 hours of educational follow-up and 2 hours of medical nutrition therapy.

The SBM recommended requiring Medicare, Medicaid, and private insurers to reimburse diabetes patients for 12 hours of DSM yearly and to eliminate the health care provider certification requirement. The SBM also suggested expanding the definition of DSM to include face-to-face meetings, group medical visits, visits with community health care workers, and use of technology-based support.—Melissa D. Cooper

Opinion: Time to Slow Incessant Bashing of Biopharmaceutical Companies

Biopharmaceutical companies have been subjected to a fair amount of criticism for skyrocketing drug prices. A recent opinion piece on the MedCity News website, however, argues that the manufacturers deserve more recognition than they get for the good that they do.

“It might be time to slow our collective role on the incessant bashing of biopharmaceutical manufacturers,” wrote Marc O’Connor, chief operating officer, Curant Health, a medication therapy management firm.

The piece primarily focused on pharmaceutical manufacturers’ patient support programs, discount pricing programs, and advances in treatment for hepatitis C.

The Humira Ambassadors program, by manufacturer AbbVie, helps patients understand appropriate injection techniques, issues medication reminders, and helps some patients access co-pay assistance. According to an AbbVie-sponsored study, mentioned by Mr O’Connor, among participants the program cut annual medical costs by 23%, disease-related medical costs by 22%, and total costs by 10%.

The piece also called attention to the many discount pricing and co-pay assistance programs pharmaceutical companies offer patients, as well as gains the companies have made that have advanced patient care—particularly for patients with hepatitis C.

“In the not-so-distant past, the capability of a biopharmaceutical manufacturer to develop a  hepatitis C cure through a single pharmaceutical therapy was considered unlikely,” Mr O’Connor wrote. “And yet it has happened … Gillead’s Harvoni and Sovaldi are actually curing people of hepatitis C.”

Compared with a liver transplant that could cost ≥$500,000, $94,500 for a 12-week course of Harvoni, Mr O’Connor wrote, “is a value-based outcome over cost result that is easy to understand.”—Jolynn Tumolo

Biosimilars Introduce New Concerns for Formulary Committees

Due to the unique characteristics of biosimilar drugs compared with small-molecule generic drugs, pharmacy and therapeutics (P&T) commit-tees will need to keep some new considerations in mind when drugs from this class are up for formulary review, according to an article in the October P&T Community.

“Formulary committee best practices for reviewing biosimilars should involve proactively planning and establishing a system to evaluate these products,” the article recommends.

 “Applying sound principles for formulary management will be critical in the objective and rational evaluation of biosimilar medicines for formulary inclusion.”

Factors to consider include:

•                Indications for biosimilar medications may not include all indications the branded biologic holds, so committees should not assume a biosimilar can stand in for an originator drug for every on-label and off-label use.

•                Naming rules have yet to be decided, but if multiple biosimilars produced by different manufacturers end up sharing the same generic name, institutional computer systems that track adverse events may need to be adapted.

•                Switching among different versions of biologics and biosimilars could cause immunogenicity reactions in patients. Therefore, when choosing a biosimilar from one of several manufacturers, chose one that has the necessary backup or multisite manufacturing capabilities to provide a reliable and consistent supply of medication.

•                When biosimilars hit the market, branded biologics may respond with significant discounts for health systems that continue to use their product. Though it might be enticing, think about how this may affect patients, who may have higher out-of-pocket costs for biologics, and how receiving a biologic while hospitalized and then switching to a biosimilar at the transition of care could impact efficacy and safety.

“P&T committee members will play a leadership role in adopting and using biosimilars appropriately through applying formulary and practice management tools and principles,” the article states.

“However, because of the variety and complexity of biosimilars, an especially in-depth analysis will be required when evaluating biosimilars for formulary inclusion.”—Jolynn Tumolo

Top-performing ACO Credits Risk Stratification With $11.9M in 2014 Savings

By focusing on patients at highest risk of hospitalization, the Premier Patient Health Care accountable care organization (ACO) generated $11.9 million in shared savings in 2014, according to a report in the Dallas Business Journal. Premier Patient Health Care, based in Carrollton, TX, ranked the highest-performing Medicare Shared Savings Program ACO in the state and third in the nation in quality and financial performance results released recently by the Centers for Medicare & Medicaid Services.

The ACO credits risk stratification software developed by Johns Hopkins University with helping it achieve the savings, the Dallas Business Journal reported. Premier Patient Health Care’s 900 physicians identified patients at greatest risk of hospitalization within the next 6 to 12 months, and then ramped up their case management, office visits, and even home health services to better their health.

“What we are doing is an integrated model to reduce duplication, improve communication, identify at-risk individuals, and meaningfully improve their care in a way that will reduce costs, which is a win-win-win for all involved,” said family physician Keith Wilkinson, MD, in the article.

Launched in late 2013, the ACO joined the Medicare Shared Savings Program in 2014 and now treats more than 20,000 Medicare patients. According to the Dallas Business Journal, Premier Patient Health Care is expanding its ACO-type management to include patients covered by commercial insurance, too.

“That also brings enhanced commercial payment rates to our physicians,” Dr Wilkinson told the publication, “which is good.”—Jolynn Tumolo

Turing Will “Somewhat” Reduce Price of Drug Amid Backlash

In September of 2015, Turing Pharmaceuticals purchased rights to Daraprim (pyrimethamine), an antimalarial medication commonly used to treat Toxoplasma gondii parasitic infections in immunocompromised patients, then increased its list price from $13.50 per tablet to $750.

According to The New York Times, at a meet-ing with critics, Turing announced that they will lower the price “somewhat” by the end of 2015. The company also announced that they will take steps to increase financial support for patients, including a patient assistance program that would expand in order to offer pyrimethamine for free to individuals with an income up to 500% of the federal poverty level.

During a recent interview, Martin Shkreli, founder, Turing Pharmaceuticals, said the reduction would be on the order of 10%, an amount not likely to mollify many people. Shkreli also said the issue was not so much the list price, since patients typically do not pay that, but rather the cost to hospitals of stocking the drug. According to The New York Times, doctors said that the higher price has made it difficult for them to obtain pyrimethamine.—Alessia D’Anna

Dartmouth-Hitchcock Leaves Pioneer ACO, Citing Flawed Penalty-bonus Formulas

Dartmouth-Hitchcock Medical Center in Lebanon, NH, recently left Medicare’s Pioneer Accountable Care Organization (ACO) initiative. The medical center told Modern Health-care it was at a disadvantage from the start: already an efficient organization before it entered the program, it did not have as much room to  improve as other less efficient practices did.

As a result of failing to meet quality and savings performance targets, the Dartmouth-Hitch-cock ACO racked up $3.5 million in Medicare penalties in its third year.

 “You are asking organizations that are already running really well to run a 2-minute mile,” CEO James Weinstein, DO, told Modern Healthcare. “It is not possible.”

Instead, the Centers for Medicare & Med-icaid Services Innovation Center should con-sider minimizing potential penalties for the most efficient organizations and minimizing bonuses for the least efficient, Dr Weinstein said. It should also give quality performance equal weight with financial performance, so efficient providers who reap quality gains are protected from penalties.

Since forming in 2012, the Pioneer ACO initiative has lost nearly half of its original members, according to the report.

“Dartmouth-Hitchcock may enter Medicare’s Next Generation ACO program, a new test of the payment model that will begin in January,” Modern Healthcare reported, “but [Dr] Weinstein said that model also has flaws.”—Jolynn Tumolo