FDA Calls for Boxed Warning on All Breast Implants

The FDA issued a draft guidance recommending that manufacturers of breast implants include a boxed warning that clearly spells out the risks of their products.
The agency also called on implant-makers to include a patient decision checklist and list the devices’ ingredients, and updated its own recommendations for implant rupture screening.
In a statement on Wednesday, FDA Principal Deputy Commissioner Amy Abernathy, MD, PhD, and Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said they got the message “loud and clear” that the regulatory body needs to do a better job protecting women considering breast implants — both from an advisory committee meeting held in March and other information-gathering efforts.
“We have heard from many women that they are not fully informed of the risks when considering breast implants,” they said. “Many stakeholders suggested that a boxed warning and patient decision checklist could provide this information.”
Suggestions for the boxed warning include the following:

• Breast implants are not considered lifetime devices

• The chance of developing complications increases over time

• Some complications require more surgery

• Implants carry the risk of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)

• Implants may be associated with systemic symptoms such as fatigue and joint pain

But the agency will still allow textured implants to stay on the market.
In July, the FDA called on Allergan to pull certain textured breast implants from the U.S. market due to the risk of BIA-ALCL. At the time, the agency said that 573 cases had been reported worldwide, with 481 linked to Allergan’s products.
FDA said makers should include the patient decision checklist as part of an informational booklet or brochure to help patients determine whether they might be a poor candidate for an implant, offering multiple examples putting individuals at higher risk of complications. For example, “I understand that if I have any of the following conditions, I may be at a higher risk for a poor surgical outcome: Medical conditions that affects my body’s ability to heal (e.g., diabetes, connective tissue disorder).”
In their example, they also urged patients to inquire about their “surgeon’s experience, education, training and credentials.”
The revised rupture screening recommendations say that asymptomatic patients with silicone gel-based implants should receive ultrasound or MRI at 5 to 6 years following an implantation, and then every other year thereafter. MRI is recommended for symptomatic patients and for those with uncertain ultrasound results for breast implant rupture.
As for the product ingredients, Abernathy and Shuren said the “FDA believes that improved access to this descriptive information will help better inform patients of the types and quantities of chemicals and heavy metals that are in breast implants.”
Writing in a JAMA Surgery “Viewpoint” article unrelated to the FDA’s announcement, Terence Myckatyn, MD, and colleagues from the Washington University School of Medicine in St. Louis, discussed the risks of BIA-ALCL and called for a “robust informed consent process” and that physicians engage in shared decision-making with patients who seek breast implants.
“In most cases, we believe that we can achieve equivalent results with either smooth or textured-surface breast implants, and that differential outcomes resulting from choosing one device vs the other are imperceptible in most cases,” they wrote. “Although the lifetime risk of BIA-ALCL is low, it is a serious risk that can be life threatening for a small subset of patients. ”
BIA-ALCL typically develops 7 to 9 years after an implantation, Myckatyn’s group noted. In about 80% of cases, patients present with a spontaneous seroma while approximately 20% present with a mass.
They acknowledged that certain situations might call for textured implants, however.
“Patients who require revision surgery owing to implant malposition can benefit from placement of a textured breast implant to reduce the risk of recurrent malposition,” said Myckatyn and co-authors. “Armed with this information, some patients do choose to accept the risks of BIA-ALCL to improve the chances of a durable cosmetic result after revision surgery.”

Myckatyn disclosed fees from Allergan Medical, RTI, and Viveve. Co-authors reported fees from Kyowa Hakko Kirin and institutional research support from Roche/Genentech, Bristol-Myers Squibb, Verastem Pharmaceuticals, and Celgene.

• Primary Source

  JAMA Surgery

  Source Reference: Myckatyn TM, et al “Breast implant-associated anaplastic large cell lymphoma: Real, rare, but avoidable” JAMA Surg 2019; DOI: 10.1001/jamasurg.2019.3154.

https://www.medpagetoday.com/washington-watch/fdageneral/82892

Treatment Still Falls Short in Majority With Rheumatoid Arthritis

More than half of patients with rheumatoid arthritis (RA) with persistent moderate-to-high disease activity after 6 months of treatment with a conventional disease-modifying anti-rheumatic drug (DMARD) did not have their therapy escalated, a U.S. registry study found.
Among 409 patients enrolled in the Corrona registry from 2014 to 2018 with moderate-to-high disease activity at baseline, and who had disease activity assessments after 6 months of DMARD monotherapy, 54% still had moderate-to-high disease, yet only 29% had any escalation in treatment, as has been recommended in international guidelines, according to Leslie R. Harrold, MD, of the University of Massachusetts in Worcester, and colleagues.

Moreover, those patients also had no improvements on multiple specific outcomes such as tender and swollen joint counts, Disease Activity Scores in 28 joints (DAS28), and Health Assessment Questionnaire (HAQ) scores, they reported online in Clinical Rheumatology.
These findings suggest that a majority of patients were not being managed with a treat-to-target approach, “despite its value being widely accepted and despite advanced therapies being readily available to treat patients after an inadequate response to conventional synthetic DMARD monotherapy,” the authors wrote.
Although the treat-to-target approach of close disease monitoring and prompt dose escalation when targets are not met after 3 to 6 months is advocated by groups such as the American College of Rheumatology, it is unclear how broadly implemented these strategies have been adopted in real-world clinical practice.
Harrold and colleagues retrospectively analyzed data from the observational Corrona RA registry, which has enrolled more than 50,000 patients since 2001.
Moderate-to-high disease activity was defined as a Clinical Disease Activity Index (CDAI) >10, and treatment escalation or advancement was defined as an increase in the dose of the original DMARD or the addition of another conventional DMARD, biologic, or targeted synthetic agent from the index visit to the 6 month follow-up visit.

Among the 409 patients included in this analysis, most were women, mean age was 66, mean duration of RA was 11 years, and mean duration of conventional DMARD therapy was 13.5 months. The most commonly used DMARD was methotrexate in 75%.
Among patients who had achieved remission/low disease activity by 6 months, improvements were seen on a wide range of specific measures, including pain, fatigue, and duration of morning stiffness.
For patients who received treatment escalation by 6 months, the change involved increase in the dose of the initial DMARD in 13%, addition of another DMARD in 8%, and initiation of a biologic in 10%.
The researchers also sought to identify patient and clinical factors that were associated with treatment escalation, finding that escalation was more common in patients who were younger (63.5 vs 66.9, P=0.007), had shorter disease duration (8.9 vs 11.9 years, P<0.001), had higher baseline CDAI (20.4 vs 17.7, P=0.008), and had daily doses of prednisone >10 mg (7% vs 1%, P=0.023).
Multiple clinical factors also were associated with treatment escalation, including:

• Higher tender joint counts, 7.3 vs 5.5 (P<0.001)
• Higher scores on patient global assessment, 46.7 vs 40.4 (P=0.021)
• Higher scores on patient pain assessment, 47.9 vs 40.3 (P=0.009)
• Fatigue, 47.8 vs 38.2 (P=0.002)
• DAS28 joint counts, 4.5 vs 4.2 (P<0.001)
• HAQ score, 0.5 vs 0.4 (P=0.035)
• Duration of morning stiffness, 114.1 vs 65.5 minutes (P=0.012)
• EuroQol 5 dimensions score, 0.69 vs 0.74 (P=0.007)

The observation that more than half of patients still had moderate-to-high disease activity at 6 months “suggests that potentially more aggressive treatment is needed across the entire population of patients with RA,” the investigators stated.
Potential reasons for the insufficient use of treatment escalation in RA include inadequate training of healthcare providers in disease assessment and patient hesitation, they suggested.
“There is considerable need for a treat-to-target approach to care to prevent joint damage and physical disability and maximize long-term health-related quality of life for patients with RA,” they concluded, adding that further work is needed to more fully examine factors that could interfere with optimization of treatment.
A study limitation was the lack of information on financial factors that may have influenced treatment decisions.

The study was supported by Corrona. Harrold and some co-authors are company employees.
The authors disclosed relevant relationships with Corrona, AbbVie, Bristol-Myers Squibb, Roche, Pfizer, Amgen, Genentech, Eli Lilly, Regeneron, and Sanofi.

last updated 10.23.2019

• Primary Source

  Clinical Rheumatology

  Source Reference: Harrold L, et al “Assessing disease severity in bio-naive patients with RA on treatment with csDMARDs: insights from the Corrona Registry” Clin Rheumatol 2019; DOI: 10.1007/s10067-019-04727-7.

https://www.medpagetoday.com/rheumatology/arthritis/82887

4 Myths on Universal Healthcare in Other Nations: None is ‘Medicare for All’

Recent polls show a majority of Americans support Medicare for All, but few seem to realize that no other system in the world operates like the current single-payer proposals in Congress. I addressed the concept of single-payer healthcare, with Cuba’s system as an example. Today I’m writing more about the ideas being discussed now in our country and how those compare to other nations that provide some type of universal care.
There are four significant misconceptions about universal health care systems that should be addressed:

1. Most universal health care systems are not highly centralized
2. Most universal coverage systems offer narrow benefit packages and incorporate cost-sharing for patients
3. Private health insurance plays a major role in most developed countries with universal coverage
4. Countries with universal coverage have strict immigration policies to control health care expenditures
Bearing these differences in mind, the Commonwealth Fund recently compared universal healthcare systems found in other countries with the U.S. single-payer bills proposed in Congress.

The country bearing the closest resemblance to the U.S. proposal, where decision-making is centralized, is France, where the government is responsible for 77% of total health expenditures. There is an out-of-pocket cost share for patients though it is relatively low, at 7% annually. The Netherlands, Singapore, and Taiwan are also highly centralized; however, they are smaller in scale – with populations similar to that of individual U.S. states – and their relative affluence allows them to sidestep long wait times.
In reality, “hybrid” systems, where decision-making and financing are shared among federal, provincial/regional, or local governments, are the most cost-effective way to deliver universal healthcare coverage to a large population. In Australia, Denmark, the U.K., and Norway, policymaking and resource allocation decisions remain centralized, yet there is flexibility within a region to distribute funds in a more individualized manner best suited to local needs.
At the other end of the spectrum are Canada, Germany, Sweden, and Switzerland, which provide “decentralized” universal health coverage, whereby decision-making and resource allocation is regulated at the regional or provincial level. In Canada, for example, each province receives per-capita block grants from the federal government. A “block grant” is a fixed amount of money the Canadian government allocates to a province in advance. Regions are usually held accountable through establishment of broad national guidelines to ensure fairness and service uniformity.
A second misnomer is that universal coverage can be delivered on a large scale with “no copays and no deductibles.” All countries with universal coverage provide a publicly-funded, basic benefits package that includes physician and hospital services, as well as inpatient (in-hospital) pharmaceuticals. However, these systems include a cost-share that patients pay out-of-pocket in order to control costs in the long-run.
Even those countries with the most comprehensive benefit plans, such as Denmark, the U.K., and Germany mandate copayments for outpatient pharmaceuticals and a cost-share for inpatient hospital stays. Out-of-pocket costs for each country range from 15% of health expenditures for Canadians, to 28% for those in Switzerland, and as high as 61% of health expenditures in Singapore. It is disingenuous for U.S. politicians to make empty promises, by promoting a system of “no copays and no deductibles” that does not exist anywhere else in the world.

It is important to clarify that nearly every country with universal coverage in the developed world is actually a “hybrid” system, mixing private insurance with publicly covered benefits to ensure access to physicians and hospitals when necessary rather than being a true “single-payer.” Canada, England, Germany, the Netherlands, Norway, Singapore, Sweden, and Taiwan all have supplementary private health insurance. France has complementary private health insurance and Australia and Denmark utilize both. 67% of Canadians purchase private insurance or have employer-based supplemental coverage for medications, mental health services, dental care, and other uncovered services.
Finally, the majority of universal healthcare systems in the developed world are considerably less “universal” when covering immigrants, who are mostly excluded. Some countries, like the U.K., insist new arrivals pay into their national system prior to obtaining health coverage. In Denmark, undocumented immigrants and visitors are covered through a voluntary, privately funded initiative by Danish doctors, the Danish Red Cross, and Danish Refugee Aid, who provide access to care.
Newcomers to Canada face an uphill battle when applying for healthcare coverage. In a nutshell, emergency medical services for immigrants are free, but access to basic medical care services is restricted and if necessary, might require out-of-pocket payment for most treatments or insurance. Those wishing to settle in Canada must pass a thorough “health screening” prior to being eligible for “universal” healthcare coverage. If the government cannot confirm that the cost of a pre-existing condition will not exceed $20,000 in annual expenditures, then healthcare coverage will be denied permanently.
When it comes to healthcare reform, our politicians need to stop trying everything else, and just do the right thing the first time. It is not Medicare for All.
Niran S. Al-Agba, MD, is a pediatrician who blogs at MommyDoc.
https://www.medpagetoday.com/blogs/kevinmd/82877

NY, states reach $700M settlement with Reckitt over opioid probes

New York and five other states have reached a $700 million settlement deal with Reckitt Benckiser over allegations that the drug distributor improperly marketed a drug to treat opioid addiction, New York Attorney General Letitia James said on Wednesday.
Reckitt in July agreed to pay up to $1.4 billion to resolve U.S. claims that its former pharmaceuticals business Indivior before it was spun out carried out an illegal scheme to boost sales of an opioid addiction treatment, Suboxone.
Indivior in April was indicted and accused of deceiving doctors and healthcare benefit programs into believing Suboxone Film, itself a form of opioid, was safer and less susceptible to abuse than similar drugs.
As part of the agreement, New York’s Medicaid program will receive more than $71.9 million in recoveries, with more than $39.9 million being returned to New York State, James said.
https://www.reuters.com/article/us-reckitt-benc-grp-probe-indivior/new-york-states-reach-700-million-settlement-with-reckitt-over-opioid-probes-idUSKBN1X22MJ

J&J: Proposed opioid settlement to lower reported third-quarter profit by $3B

Johnson & Johnson (JNJ.N) on Wednesday lowered its previously reported profit for the third quarter to $1.8 billion from $4.8 billion to account for a proposed opioid settlement payment.
The company lowered its earnings per share for the quarter to $0.66 from $1.81, and said there was no impact to its adjusted earnings numbers.
A framework deal, announced on Monday, was hammered out by some companies and attorneys general in North Carolina, Pennsylvania, Tennessee and Texas, and will need broad support among the state attorneys general and local governments that sued several drugmakers and distributors over the opioid crisis.
J&J said it could not predict when or if the deal would be finalized.
https://www.reuters.com/article/us-usa-opioids-jnj/johnson-johnson-says-proposed-opioid-settlement-to-lower-reported-third-quarter-profit-by-3-billion-idUSKBN1X22PX

Earnings after Thursday’s close

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Earnings before Thursday’s open

AZN, BAX, DHR, GNC, SCHN
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