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Monday, April 26, 2021

Rheumatic Patients Should Proceed Cautiously After COVID Vax

 On the heels of the announcement of depressed antibody responses to COVID-19 vaccines in transplanted patients, the first question that came to my mind as a practicing rheumatologist was: Does this important and frightening finding also apply to our patients with autoimmune diseases on immunosuppressants?

Fortunately, we have also been studying patients with rheumatic and musculoskeletal diseases (RMD) in our national study of vaccine immune responses. Among 123 COVID-19-naive patients with autoimmune disease -- inflammatory arthritis, systemic lupus erythematosus, or other connective tissue diseases -- who received a first dose of mRNA vaccine, 74% had detectable antibodies to SARS-CoV-2.

While there were no statistically significant differences between those on immunosuppression compared with those not on therapy, RMD patients on biologic or non-biologic disease-modifying antirheumatic drugs (DMARDS) had an absolute 15% decline in antibody response -- 67.5% of those taking biologic or non-biologic DMARDS had detectable antibodies versus 82.4% of those not taking them.

Strikingly, detectable antibodies were identified in only 27.3% of patients on mycophenolate (compared with 70.3% of those taking other non-biological DMARDs) and in just a third taking rituximab (compared with 76.2% for those taking other biological DMARDs).

RMD patients had an overall better antibody response (74%) when compared to transplant patients (17%). While both groups of patients are on immunosuppression, the impact of immunosuppression on vaccine response was not as severe in the RMD population. One reason for this difference may be the fact that RMD patients take a greater heterogeneity of immunosuppressants, many of which did not severely dampen the antibody response.

Nevertheless, there were also similar groups (those on mycophenolate) who had a very low antibody response in both transplant and RMD patients. Until we better understand the mechanisms behind the differential response, any patient who is immunosuppressed should remain cautious even after vaccination. We anticipate the antibody response results following the second dose of the mRNA vaccine will also shed further light on the efficacy of these vaccines in this vulnerable population.

The major implications from our study are that our rheumatic patients are not fully immune after the first dose of the vaccine, and that the response is particularly curtailed in those taking mycophenolate or rituximab. Rituximab is well known to severely dampen antibody responses, and the American College of Rheumatology Vaccine Task Force has provided clear guidelines on the timing of COVID-19 vaccinations with rituximab administration. However, this is not the case for mycophenolate.

Therefore, modified guidelines in holding immunosuppression -- when safe to do so -- may need to apply more broadly to other immunosuppressants such as mycophenolate. Furthermore, antibody testing can be a very useful tool to assess vaccine response, especially in vulnerable groups, such as those on mycophenolate or rituximab. Lastly, it is imperative that patients with RMDs on immunosuppression talk to their providers before relaxing precautions, even if they have received a vaccine.

Julie J. Paik, MD, MHS, is an assistant professor of medicine and director of clinical trials at the Johns Hopkins Myositis Center in the Division of Rheumatology at Johns Hopkins University School of Medicine in Baltimore.

Dorry Segev, MD, PhD, is a professor of surgery and epidemiology and associate vice chair of surgery at Johns Hopkins University School of Medicine and Bloomberg School of Public Health.

https://www.medpagetoday.com/rheumatology/generalrheumatology/92255

COVID Vaccines More Available, but Mostly Not in Doctors' Offices

 Even as the supply of COVID-19 vaccines continues to increase, many doctors clamoring to distribute the vaccine directly to their patients are finding their requests go unheeded, experts say.

"Leaving physician practices out makes no sense at all because patients trust physicians on vaccines more than they trust anybody else," said Bob Doherty, senior vice president of governmental affairs and public policy at the American College of Physicians and a MedPage Today editorial board member. "Patients need to be able to get vaccines from their personal physician, who can reassure them about the safety of the vaccine, and also monitor the potential side effects. But right now, many primary care physicians have not been included in the distribution plans at all."

"I think it's a great idea," said Yalda Jabbarpour, MD, medical director of the Robert Graham Center at the American Academy of Family Physicians, and a family physician herself. "That's where people usually get their vaccines -- the primary care office."

Additionally, studies have found that "most Americans, their trusted source of information about vaccines, and particularly the COVID vaccine, is their primary care provider. Anecdotally, I've been seeing that like crazy. The second the Pfizer vaccine got emergency use authorization, patients were calling off the hook: When would they be eligible? How do they get the vaccine? Patients who have vaccine hesitancy wanted to talk to me about my experience getting the vaccine," she said.

Maryland's Distribution Program

There is at least one state government that's getting on board with distributing to physician offices. Under the Maryland Primary Care Program -- which provides funding for delivery of advanced primary care to 562 practices statewide -- COVID-19 vaccines have been distributed to 236 practices, said Howard Haft, MD, the program's director, who spoke during a phone interview at which a public relations person was present. "Primary care doctors have been clamoring to do COVID vaccinations since the beginning of the pandemic," he said. "As we developed vaccines, they were front and center, saying, 'we're here and ready to do that.'"

Haft said the rollout in Maryland is "going very, very well; we look at how quickly the primary care physicians are able to use the vaccine, and essentially they use it all within the week they get it, and they actually could use more." Unfortunately, however, the state "is limited by the amount the federal government gives us each week," he added.

The program "is really addressing the issue of health equity," he continued. "They're able to use the data the state provides to them to understand which of their patients are already vaccinated and which have not been, and they can also tell by race, ethnicity, age, and underlying medical condition, so they can reach out to the older [patients], those who have other barriers ... and may not have been as equally immunized as others, and they're able to bring that back into perspective and deliver vaccines in an equitable fashion."

The state is distributing only the Moderna and Johnson & Johnson vaccines because the Pfizer vaccine only comes in lots of about 1,000 vials, "which is a lot for a primary care practice to store and use in a relatively short period of time," Haft said. (A Pfizer spokesman said that although the vaccine lots are large, there are multiple options for vaccine storage, including commercially available ultra-low-temperature freezers that can extend storage for up to 6 months, as well as the shippers in which the vaccines arrive, which can be refilled with dry ice to allow storage for up to 30 days.)

Vaccines are shipped directly to the practice from the distributor or the manufacturer, and arrive Monday morning each week via Federal Express or UPS, Haft said. "Every Monday or Tuesday they fill out a survey and say how many doses they'd like for the next week ... Everybody gets at least 100 doses and it could go up to -- the sky's the limit."

Interest From the White House

Haft said he has heard from other states interested in Maryland's program, and also from the Biden administration. "The White House chief of vaccines has been interested, and will be visiting some practices here in the near future," he said. The state plans to continue expanding the program, with a short-term goal in the next few weeks of hitting 400 practices.

The Biden administration has publicly said it is interested in the idea of distributing vaccines through doctors' offices. "We're relying on local voices and local doctors to provide the best information, which every set of data we've seen, and even from some news organizations, show that those are the most trusted messengers," said White House Press Secretary Jen Psaki at an April 21 press briefing. "Along with the CDC, we're working to help states expand vaccine distribution to primary care physicians."

California is also including providers in its distribution efforts. Any provider can sign up through its myCAvax website to become a vaccine provider, although the process can be a little cumbersome, noted Anthony York, spokesman for the California Medical Association. "We're helping identify local providers, physicians, and also helping individual physicians navigate the process," York said in a phone interview. "We've been engaged for several weeks in terms of trying to identify where the need was going to be" to get vaccines into arms.

Some Doctors Taking the Reins Themselves

In some states, doctors -- particularly oncologists -- are acting on their own. Kashyap Patel, MD, an oncologist in Rock Hill, South Carolina, petitioned his local government for weeks to be able to distribute COVID-19 vaccines to his patients. "We got approved this week," Patel said in an interview last week. "We will get our supply this Friday and will do it next week. We are in the process of figuring out who we are going to vaccinate first." He noted that half of the patients in the state are not yet vaccinated, and many still have reservations about the vaccines and their side effects.

Cancer patients are good targets for office-based vaccination because their chances of getting the coronavirus are higher than the normal population, "and if they get it, they have a three to five times higher chance of being hospitalized or dying," said Patel, who is also president of the Community Oncology Alliance, an association of community-based oncology practices.

To identify patients who should get the vaccine, "we're going to create an algorithm from our electronic health records, pull out the patients we deem at highest risk, and start calling them on the phone, explaining that this is an option we recommend strongly that they do it," he continued, adding that the first shipment will contain 50 doses of vaccine.

Maen Hussein, MD, an oncologist in The Villages, Florida, has been mounting a similar effort. In Florida early on, vaccines were difficult to come by, with many available only through the Publix chain of supermarkets and pharmacies. "It was very hard to get an appointment because patients had to go online ... and lots of patients were complaining that they didn't know how to use a computer," he said. Even those who were computer-savvy had difficulties: "It took my wife 2 hours to get an appointment for her mother."

Oncology practices are good places to distribute vaccines because cancer patients who receive chemotherapy may be immunosuppressed for a week or 10 days, and therefore shouldn't be vaccinated during that time. "This way we can control when we give patients their vaccines, because I know their treatment schedule," he said. "That's why a cancer practice is different than primary care, whose patients are mostly healthy or have issues that won't interfere with the vaccine."

Initially, the county was only willing to give Hussein's practice 300 doses, and those had to be given to county residents even though patients also came from other counties, he said. Eventually, that restriction was relaxed, and within a few weeks, the practice was receiving 5,000 doses. "We started to give it to other offices and opened on Saturdays and Sundays" for vaccinations, he added. "We really try hard not to waste any doses."

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/92285

90% of J&J vaccines unused at Central Florida FEMA site

 Turnout has been so low for the Johnson & Johnson single-shot vaccine at Florida's FEMA-run sites that about 90% of the supply has gone unused following a 11-day pause, health officials said.

The federally-run vaccine site at Valencia College’s West Campus in Orlando only administered 268 doses of the 3,000 Johnson & Johnson vaccines that were available on Sunday, site spokesman Ian Ohlin told the Orlando Sentinel.

For much of the day, there was “little to no wait,” Ohlin said.

A similar story played out in Miami, where by Monday afternoon, officials at the Miami had only administered 303 doses of the vaccine of about 3,000 that were available.

Shirley Harrison had planned to receive the single-shot vaccine Sunday, she told WSVN-TV.

“I heard was going on, and I just changed my mind. I said, ‘I’ll do Pfizer,’” she said.

Late Friday, the Food and Drug Administration and the Centers for Disease Control and Prevention lifted the pause, which began after 15 women, out of nearly 8 million people who received the vaccine, developed blood clots.

A federal advisory panel decided the benefits far outweighed the risks.

The Florida Division of Emergency Management tweeted that it was resuming the Johnson & Johnson shots on Sunday at the vaccination sites in Tampa, Orlando, Jacksonville and Miami after reviewing guidance from the Centers for Disease Control and Prevention and the Food and Drug Administration.

“The bottom line is, now you have options, you have choices, so you can get the Pfizer first-dose vaccine here at Miami Dade College North, or you can get the J&J vaccine,” the state agency's spokesman Mike Jachles told WSVN. “That’s an individual decision. If you have any conditions or any concerns, we urge you to speak to your health care provider first to see which vaccine is best suited for you.”

Valeria Ibarcena, 29, of Miami, said she decided to get the J&J vaccine, convinced the chances of developing blood clots were slim.

“The sample was very small. This side effect outweighs getting COVID, which is a serious disease. The J&J is one shot and you are done. Now I can go out with some confidence, even while wearing a mask,” Ibarcena said.

Through Sunday, 8,562,544 people in Florida have received at least one vaccination shot including 5,798,487 who have completed their shot regimen, whether it’s the two-dose Pfizer or Moderna option or the one-dose Johnson & Johnson vaccine, state health officials said Sunday.

Also on Monday, the state added 3,513 positive COVID-19 cases to bring the total to 2,212,097. Florida's COVID-19 death toll stands at 35,600, health officials reported.

https://www.clickorlando.com/news/florida/2021/04/26/super-low-turnout-90-of-johnson-johnson-vaccine-unused-at-central-florida-fema-site/

WV Gov: State to use COVID stimulus funds to give all residents 16-35 $100 savings bond

 The state will give a $100 savings bond to each West Virginian from age 16-35 who takes a COVID-19 vaccine. West Virginia will use federal COVID-19 stimulus funding to finance the program.

Gov. Jim Justice announced the savings bond plan Monday in a bid to get more COVID-19 vaccine shots in arms in West Virginia. He said the plan had been "vetted [in] every way in the world." He added that he had made the decision "if we want to really move this needle, and we want to move it right now."

"I'm telling you, West Virginia, it's time to shut this thing down" unless state residents want COVID-19 to "linger forever."

The governor later in his news conference said he's hopeful the state will be able to give all those 16-35 savings bonds, and added that he believes a savings bond would be something meaningful to look at it in the future, rather than "just ... a dash in the pan and a couple of trips to Wendy's with your friends."

Justice estimates the initiative could cost $27.5 million if it's wildly successful. If there aren't enough savings bonds available, the state will hand out cash, Justice said.

"But if we did that ... it would be the best money ever spent, like you can't imagine," Justice said.

Justice also went over the many ideas submitted and kicked around to boost the numbers of those being vaccinated.

The governor indicated state officials have received "lots and lots of good ideas here, but I am telling you, we need to kickstart this, and kickstart this in a big way."

He added, "maybe just a real dose of patriotism from the standpoint of a savings bond" would be meaningful to the young. "Our young people should be really, really proud if they help us step up," Justice said.

He said without vaccine buy-in from many more people, he would be "reading names" of the pandemic dead every other day, "and also we're going to be faced with wearing these masks that nobody likes for a long, long, long time."

But if young people "step up in masses, we'll be done, and we'll be done soon" with COVID-19.

Dr. Clay Marsh, who leads the state's medical response to COVID-19, said the state is "at a critical point in this pandemic response," with people choosing to be vaccinated, plus wearing masks and staying physically distanced, pivotal at this inflection point in Mountain State history. Marsh added that the vaccines are "incredibly effective" and "incredibly safe." All of his close loved ones have been vaccinated, Marsh added.

James Hoyer, who leads the West Virginia vaccine effort, said the state is "doing exceptionally well" with residents getting their second vaccine. He said it's key to get the second vaccine to have full immunity. 

Justice added that vaccines would be offered at the state basketball tournament in Charleston, via the Kanawha-Charleston Health Department, and likely would be added through mobile units at fairs, festivals and other events.

A total of 700,260 residents, about 52%, now have received at least one COVID-19 vaccine dose, while 558,785 are fully vaccinated. The state has about 1.792 million people in all, but only those who are 16 and older — about 1.47 million — are eligible to be vaccinated.

Justice fears that about 40%, or 588,000, of the 1.47 million are hesitant or just don't want to be vaccinated. He indicated the approximately 380,000 residents from age 16-35 are especially hesitant. Justice is hopeful the savings bond initiative with the young will result in an 80% participation rate, adding 275,000 to the state's total, and putting the overall vaccination rate in West Virginia at around 71%.

The state's variant numbers, according to Marsh: 471 of the United Kingdom variant, and it's spreading in the 10-35 age group' 215 cases of the Brazilian variant; and two cases of the South African variant. Marsh noted that as variants continue to mutate, they will come in "more and more and more deadly" forms.

Justice began by noting the loss of eight more individuals to COVID-19 since Friday's briefing.

"Considering where we've been, it's a good number, and we want to continue to be at this level, or less and less, and finally we'll get to zero," the governor said.

The state now has 2,821 deaths since the beginning of the pandemic in West Virginia in March 2020. However, that number will fall by 162 Tuesday, according to Dr. Ayne Amjad, state health officer. A review of deaths listed as COVID-19-related ended up not being attributable to the virus, Amjad said. She added that the state is continuing to work toward rolling out an electronic death reporting system.

https://www.wvnews.com/news/wvnews/west-virginia-gov-justice-state-will-use-covid-19-stimulus-funds-to-give-all-residents/article_3464b366-a6af-11eb-8cef-a3be246c97ac.html

Vital to get U.S. vaccine help along border: Mexican official

 Mexico is ramping up requests for more COVID-19 shots from the United States, and in the coming days may ask for assistance vaccinating people along the countries' shared border, the Mexican government official in charge of vaccine diplomacy said.

Mexico has received 2.7 million doses of AstraZeneca's COVID-19 vaccine from the United States, but has not made progress on accessing larger U.S. stocks, deputy foreign minister for multilateral affairs Martha Delgado said in an interview with Reuters late last week.

"We are once again taking up dialogue to insist on this need," she said, ahead of an upcoming visit by Foreign Minister Marcelo Ebrard to the United States.

Mexico may also put forward a proposal to prioritize vaccination along its border with the United States, Delgado said, describing the issue as important and a concern in Mexico.

The proximity and human ties between populous towns and cities along the border means it is easy for the coronavirus to reinfect both sides.

The U.S.-Mexico border region, which stretches 3,175 km (1,973 miles), is home to at least 14.6 million people, according to government data from 2018.

Tens of thousands of Central Americans have trekked to the U.S. border in recent months, in a growing humanitarian challenge for U.S. President Joe Biden. Delgado did not specify whether a new proposal for vaccines in the border area would include migrants.

The supply of vaccines has become a global diplomatic tussle.

Mexico government officials on Friday declared the doses of AstraZeneca's vaccine shipped from the United States safe and approved by two health regulators after operations were halted at the U.S. plant that produced them due to contamination.

Following Delgado's interview with Reuters, a representative for her declined to comment on whether the issue could impact future vaccine agreements with the United States.

Ebrard will also make trips to Russia, China and India, as part of efforts to ensure supply agreements are honored.

Part of his agenda in the United States will be devoted to vaccines, including "scientific exchange," Delgado said.

Mexico has so far received more than 21 million shots, primarily from Pfizer, AstraZeneca, China's Sinovac and Cansino and Russia's Sputnik V.

But supply delays and shortages have hampered the campaign to vaccinate its population of 126 million.

The country has relied on deals with China and Russia amid gaps by Western suppliers and slow shipments through global COVAX facility mechanism, led by the GAVI vaccines alliance and the World Health Organization to promote equitable access.

Mexico was considering hosting Phase III trials for an additional Chinese vaccine, Delgado said. She declined to say which one.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/Important-to-get-U-S-vaccine-help-along-border-Mexican-official-says-33067760/

U.S. to Share AstraZeneca Covid-19 Vaccine Doses With World

 The U.S. government plans to share as many as 60 million doses of the AstraZeneca Covid-19 vaccine with the rest of the world, the White House said Monday.

"The administration is looking at options to share American-made AstraZeneca vaccine doses during the next few months," White House press secretary Jen Psaki said, adding that the U.S. was confident in its supply of other available vaccines. "Given AstraZeneca is not authorized for use in the United States, we do not need to use AstraZeneca in our fight against Covid over the next few months."

Ms. Psaki said the Food and Drug Administration would confirm that all AstraZeneca doses meet safety expectations before they are shipped from the U.S.

The Biden administration has faced growing pressure to share vaccine doses with developing countries and other nations that have been hard-hit by the coronavirus pandemic. A surge in India, which for the fifth consecutive day set a record for the world's largest single-day increase in new cases, prompted calls for the U.S. to share its AstraZeneca supply with the Indian government as the latter struggles to vaccinate its population.

AstraZeneca declined to comment on whether it was consulted on the decision. "The doses are part of AstraZeneca's supply commitments to the U.S. government," a spokeswoman for AstraZeneca said in an email. "Decisions to send U.S. supply to other countries are made by the U.S. government."

The Biden administration said last month it would share roughly four million doses of the AstraZeneca vaccine with Mexico and Canada. The White House said at the time those doses would be seen as a loan, with the expectation that the nations would send doses to the U.S. later.

The Biden administration has said it has secured enough doses to inoculate the eligible U.S. population. But officials have said the U.S. needs to hold on to additional doses for possible booster shots and for when the vaccine is authorized for children.

Meanwhile, U.S. officials have turned from managing a flood of interest in the vaccines to persuading people who are unsure about getting it. The U.S. weekly average of vaccine doses administered, which has been generally rising since mid-December, ticked down recently.

AstraZeneca has encountered setbacks in meeting its supply agreements. The European Union said Monday that it was suing AstraZeneca for failure to deliver on its Covid-19 vaccine contract.

Reported cases of rare blood clotting in Europe raised concerns recently about the AstraZeneca vaccine's safety. European regulators have said the benefits of using the vaccine outweigh its potential risks, but they recommended that EU governments add a warning to the vaccine's product information.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/U-S-to-Share-AstraZeneca-Covid-19-Vaccine-Doses-With-World-3rd-Update-33072376/

Reata: FDA accepts filing for chronic kidney disease med

  Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” or “we”), a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (“FDA”) accepted for filing the New Drug Application (“NDA”) for bardoxolone methyl (“bardoxolone”) for the treatment of patients with chronic kidney disease (“CKD”) caused by Alport syndrome.

This NDA submission is based on the efficacy and safety data from the CARDINAL Phase 3 clinical trial. The FDA will review the application under a Standard Review timeline. The Prescription Drug User Fee Act (“PDUFA”) date, the FDA action date for the application, is scheduled for February 25, 2022. The FDA also advised the Company that it is currently planning to hold an Advisory Committee meeting to discuss the application.

“We are pleased with the FDA’s decision to accept for filing our NDA for bardoxolone and look forward to continuing to work with the Division during the review process,” said Warren Huff, Reata’s President and Chief Executive Officer. “Alport syndrome is one of the most rapidly progressive forms of CKD and a truly devastating disease to those patients and the families who are affected by it. If approved, bardoxolone may be the first therapy to slow the progression of kidney disease in patients with this serious and debilitating disease.”

https://finance.yahoo.com/news/reata-announces-fda-accepted-filing-205400827.html