What's Really Driving COVID 'Rebound' After Paxlovid?

 In the early days of the pandemic there was an understandable rush to define and optimally treat COVID-19. Anecdotal evidence and the opinions of eminent scientists and non-scientists overwhelmed social and mainstream media platforms only to eventually be overruled by the results of careful, scientific analyses and well-designed clinical trials. Now, more than 2 years into the pandemic, we must return to the standard of careful and thorough analyses for all interventions and treatments.

The debate about "COVID-19 rebound" after nirmatrelvir/ritonavir (Paxlovid) treatment is one of these timely areas warranting further investigation. Continuing down the current path of uncertainty has consequences for how and by whom this antiviral should be used. However, by applying lessons learned from the early days of the pandemic -- including acknowledging the importance of randomized controlled trials (RCTs) -- we can avoid repeating the same mistakes. To do this, it is necessary to start by defining the question, identifying current knowledge gaps, and only then can one propose scientific solutions to bring a rapid resolution to the COVID-19 rebound controversy.

The Need for a Sound Definition Before Studying COVID-19 Rebound

Paxlovid consists of two drugs: nirmatrelvir, which inhibits a SARS-CoV-2 protease inhibiting viral replication, and ritonavir, which slows the inactivation and breakdown of nirmatrelvir. Per a CDC health advisory released in May, COVID-19 rebound is defined as a return of symptoms or a "new positive viral test after having tested negative" occurring "2 to 8 days after initial recovery." We just saw this over the weekend in the case of President Biden.

This definition of rebound is challenging and prone to inflating the incidence of rebound. It is possible some individuals identified as having "Paxlovid rebound" may have been experiencing a waxing and waning of COVID-19 symptoms while some unknown number of other reported rebound cases could be due to the known limitations of COVID-19 testing.

First, infectious disease specialists have long witnessed that some respiratory illnesses can have a bimodal course. This phenomenon has been reported in patients with COVID-19, albeit best described in hospitalized patients with more severe disease. Additionally, secondary bacterial infections (e.g., sinusitis, bronchitis, pneumonia) have been known to occur after COVID-19, which could also be misidentified as COVID-19 rebound.

Second, COVID-19 antigen testing -- a convenient diagnostic tool -- does have limitations. It is plausible, for example, that some individuals, after getting COVID-19 and completing a course of nirmatrelvir/ritonavir, initially get a false negative test (especially if they have a low viral load); then, after testing again out of precaution a few days later, could get a positive result due to viable or dead viruses -- an antigen test cannot distinguish between them. Finally, some patients who have clinically recovered will continue with positive PCR COVID-19 testing for several weeks, which could explain some of the anecdotal reports of COVID-19 rebound.

Third, recall bias is another challenge to defining COVID-19 rebound and its incidence. It is a well-known phenomenon that patients who receive a particular therapy are more likely to report side effects or symptoms during their clinical course compared to individuals who are not treated. Thus, the problem of identifying cases of COVID-19 rebound solely based on observational or anecdotal reports, and not as part of a controlled trial, is that the number of cases may be falsely increased.

Few Studies Specifically Describe Paxlovid Rebound

The data supporting the existence of COVID-19 rebound after nirmatrelvir/ritonavir treatment is limited. Most studies were conducted prior to the emergence of Omicron and employ a retrospective design prone to various biases. Nonetheless, the data suggest the rebound phenomenon may occur in only a small number of high-risk patients and the findings to date don't offer sufficient evidence that it is definitely a result of nirmatrelvir/ritonavir.

A secondary analysis of the EPIC-HF trial (the basis for the antiviral's authorization) revealed that approximately 1% to 2% of all unvaccinated individuals (treated and untreated) tested positive after having a negative test. And a recently published study showed that COVID-19 rebound occurred in only four of 483 (0.8%) vaccinated, high-risk patients. The incidence of rebound among vaccinated and unvaccinated patients infected with the Omicron variant is unknown.

There are three notable, albeit small, case reports recently published in the medical literature regarding COVID-19 rebound after nirmatrelvir/ritonavir treatment. One non-peer-reviewed study describes 10 patients who experienced a relapse of symptoms and SARS-CoV-2 viral load following treatment with nirmatrelvir/ritonavir. The authors identified two instances of transmission during relapse. The second report, also not yet peer-reviewed, describes a single patient who experienced the return of symptoms and had culturable virus 5 days after completing a nirmatrelvir/ritonavir course. Because nirmatrelvir/ritonavir viral resistance was not noted nor did the patient demonstrate an absence of neutralizing antibodies, this raises the question of whether rebound could be a function of drug level in the individual's blood (while the dosage in the antiviral pill is consistent, not everyone absorbs the same amount or metabolizes it the same way). The third and most recent study has been peer-reviewed and describes a series of seven patients who experienced COVID-19 rebound, six of whom had recurrence of symptoms and one who was asymptomatic but had a repeat positive antigen test. While also limited in size, this study supports the findings of the previous two studies: three of the seven patients had culturable virus, suggesting that patients who experience COVID-19 rebound after nirmatrelvir/ritonavir may be infectious. However, there is no defined level of culturable virus that can identify patients who remain infectious/contagious. And fortunately, sequencing of SARS-CoV-2 virus from six of the seven patients did not identify any known antiviral resistant mutations.

Studies That Could Shed Light on Paxlovid Rebound

The EPIC-SR trial enrolled 1,553 individuals between August 2021 and December 2021 with confirmed SARS-CoV-2 who had a standard risk of progressing to severe disease. Pfizer has shared some of these results; however, these press releases have not mentioned COVID-19 rebound.

Another study, the PANORAMIC trial, is currently enrolling high-risk outpatients in the U.K., but like the EPIC-SR trial, it is unclear if rebound is among the study outcomes.

Together, these studies have the potential to both further define and report the incidence of rebound after nirmatrelvir/ritonavir. If these data were collected from the EPIC-SR trial then it should be released. And if the PANORAMIC trial is not already designed to identify cases of rebound, then the protocol should be amended accordingly.

Only an RCT Can Definitively Answer the Question of Paxlovid Rebound

Whether nirmatrelvir/ritonavir is associated with COVID-19 rebound and how often this occurs can only be determined by a prospective double-blind RCT. The basis for the standard of care of hospitalized COVID-19 patients was largely defined by the results of large RCTs that meticulously detailed adverse events. In a similar fashion, an RCT performed with individuals at low risk for progression to severe disease who have been vaccinated or previously infected with SARS-CoV-2 need to be randomized to placebo or nirmatrelvir/ritonavir and then followed closely for rebound by evaluating symptoms, signs, and serial collection of both molecular tests and viral cultures, in conjunction with monitoring of close contacts to determine whether this is transmissible. This will define more precisely the rebound prevalence, clinical consequences, and infectiousness rates. One could also test to see if there is any benefit to treating rebound with an additional course of nirmatrelvir/ritonavir. Despite reports of nirmatrelvir/ritonavir being prescribed to treat rebound, the CDC is not currently recommending this approach.

Without such a scientifically rigorous study, uncertainty will persist at a dire cost. Not knowing who best benefits from nirmatrelvir/ritonavir can result in its overuse, more drug-induced side effects, and the development of viral resistance. Additionally, some individuals who would benefit from nirmatrelvir/ritonavir may be hesitant to be treated because of the perceived risk of COVID-19 rebound. On the other hand, if COVID-19 rebound does occur due to nirmatrelvir/ritonavir, then it is important to know the incidence, clinical, and microbiologic course, and whether additional treatment with nirmatrelvir/ritonavir is warranted.

Once again, the pandemic reminds us to hurry but not rush to judgement, to conduct well-designed clinical trials, and to learn from the results to improve patient care.

Daniel A. Sweeney, MD, is an associate clinical professor of medicine at the University of California San Diego. Cameron R. Wolfe, MBBS, MPH, is an associate professor of medicine at Duke University in Durham, North Carolina. Andre C. Kalil, MD, MPH, is a professor of medicine at the University of Nebraska Medical Center.

Disclosures

The authors reported no conflicts of interest.

https://www.medpagetoday.com/opinion/second-opinions/100016

U.K. Hospital Trialling Cleaning Solution That’s ‘Better Than Bleach’

 A new cleaning solution clean can hospitals better than traditional products, U.K. researchers say.

The product – Pathisol – can disinfect a surface in two minutes, which is five times faster than bleach. It can also kill 99.99% of pathogens, including hospital superbug Clostridium difficile.

A team of researchers at Teeside University have been running an independent trial of the new product at North Tees and Hartlepool Foundation Trust in northern England.

Developed by hospital subsidiary NTH Solutions, it contains a chemical called “hypochlorous acid”, which is already used widely in the US.

“We know hypochlorous acid works from studies done in the U.S., but there isn’t yet clear evidence that it is effective in an acute clinical environment such as an NHS hospital,” NTH Solutions’ Educational and Development lead Dan Sullivan told Forbes.

“Our study aims to provide that evidence through a robust, independent trial set in live clinical environments.”

Lead nurse at North Tees and Hartlepool Rebecca Denton Smith added: “Pathisol is a natural product. It's known as hypochlorous acid, and it's found in our bodies.

“It’s our natural first-line defence against infection. It can be easily made, easily applied and, most importantly of all, it kills a wide range of pathogens.”

As well as being safer, cheaper to make and less harmful to the environment than bleach, the firm says Pathisol can be made onsite at hospitals, which may reduce the need for plastic bottles.

The trial, which has three phases, is still underway, with earlier research efforts delayed by the pandemic. But it’s already showing positive results.

During the first phase, researchers swab random locations across three hospital wards, before sending samples for testing at the hospital’s microbiology lab.

There, they are left for 24 hours to see what colonies grow. This gives researchers a baseline understanding of the pathogens that live in each ward when they’re cleaned as normal.

In the second phase, the normal cleaning solution is swapped for Pathisol.

In the third, researchers are trying a new method of applying hypochlorous acid: spraying it on to surfaces with hand-held electrostatic devices.

Swabs from each phase of the trial are compared with previous results to work out how effective the new solution is.

So far, results have been positive, both for Pathisol and the new application method.

Dan Sullivan said: “We are awaiting independent verification of the data, but early indications are that Pathisol has successfully reduced microbial load across the trial areas with an enhanced reduction when electrostatic technology was applied."

Teeside University plans to publish the data in due course.

The firm’s environmental and decontamination services manager Tony Sullivan said these promising results could translate into tangible benefits for hospitals.

He said: "Pathisol can take up to 2 minutes to disinfect a surface, whereas bleach can take up to 10 minutes. In National Health Service terms, that means we can turn a bed around 5 times faster by using [the product] to disinfect, and we can deep clean a ward without having to evacuate it for 24 hours."

https://www.forbes.com/sites/katherinehignett/2022/08/04/uk-hospital-trialling-cleaning-solution-thats-better-than-bleach/

Biden tests COVID-19 positive for sixth straight day

 President Biden tested positive for COVID-19 again on Thursday but feels “very well,” his physician, Kevin O’Connor, said in a new update two weeks after the president first tested positive.

Biden has tested positive for six days with a rebound COVID-19 infection that has been seen in some patients who take the antiviral treatment Paxlovid. He first tested positive for COVID-19 on July 21 and ended his isolation last week before testing positive again on Saturday.

“The President feels very well today. He is still experiencing a very occasional cough, but the cough is improving. His temperature pulse, blood pressure, respiratory rate and oxygen saturation remain entirely normal. His lungs remain clear,” O’Connor wrote in a memorandum released by the White House. 

“This morning, his SARS-CoV-2 antigen testing remained positive,” he added.

Biden is expected to continue to isolate in the White House residence until testing negative. 

On Wednesday, the president enjoyed a “light workout” and also had no fever and his vital signs remain normal, according to O’Connor. His loose cough returned on Tuesday.

Biden has hosted multiple virtual events this week while in isolation. On Thursday afternoon, he will host a roundtable event with business and labor leaders to discuss the Inflation Reduction Act.

https://thehill.com/homenews/administration/3588071-biden-tests-covid-19-positive-for-sixth-straight-day/

U.S. Regulators Announce Plans for Monkeypox Antiviral Trial

 To deal with the rapidly rising monkeypox cases in the country, experts from United States health regulatory agencies have announced plans to conduct a clinical trial to more thoroughly assess the safety and efficacy of TPOXX (tecovirimat) as an antiviral in patients with monkeypox.

TPOXX, developed by the New York-based pharma firm SIGA Technologies, is already approved for use in humans—but only as a treatment for smallpox. The U.S. Food and Drug Administration (FDA) has yet to give it the greenlight for monkeypox. Instead, patients and their doctors have to go through a stringent and cumbersome “compassionate use” process before the drug can be dispensed. Not many doctors are willing to jump through these hoops, and as a result, very few patients have received TPOXX.

According to a CNN report, as of July 22, TPOXX has been administered to over 223 patients, way below the more than 5,000 confirmed or probable infections at the time. As of this writing, there are 6,617 confirmed monkeypox cases across the country.

FDA approval would quickly get the TPOXX pills to those who need them the most. Supply wouldn’t be an issue, either, as before the current outbreak, the U.S. Strategic National Stockpile had some 1.7 million available courses of the drug.

Patients, health advocates and even physicians have expressed frustration at how the drug, despite being available and abundant, continues to be inaccessible. The situation is even more frustrating since TPOXX can already be used to treat monkeypox in other jurisdictions. The European Union gave the drug its nod in January this year, and the U.K. followed suit in July.

In an article published Wednesday in The New England Journal of Medicine, regulatory experts stood by their decision to still require a clinical trial before approval in the U.S. The authors are from the National Institute of Allergy & Infectious Diseases, the Centers for Disease Control and Prevention and the FDA.

When TPOXX was approved for smallpox in 2018, the disease had virtually been eradicated. And even if it hadn’t been, smallpox is such a severe and lethal condition that there would be no ethical way to conduct human trials.

Things are different for monkeypox, the NEJM authors argued: Human trials for monkeypox are not only ethical and feasible but would also be for the best, according to them. Instead of basing safety and efficacy data on animal models, human studies will allow for a more accurate, true-to-life estimation of the drug’s performance.

The exact details of the trial—such as its specific design, planned doses and a more fleshed-out schedule—remain hazy as of the moment. But Phillip Gomez, CEO of SIGA, told BioSpace that “[r]egarding the timeline for the randomized clinical trial, SIGA is working closely with NIAID and it is anticipated that the study will start within weeks.”

Gomez adds that SIGA is also working with various governments who want to secure their national stockpiles of TPOXX, even ahead of regulatory clearance.

In the meantime, however, patients have little choice other than to wait for the trials to complete—or to try their luck (and persistence) at the FDA’s compassionate use system. In this regard, at least, regulatory agencies recognize that some of their requirements may be excessive and have been working to streamline the application process by reducing the amount of data and paperwork needed.

Agencies say that they will continue to accept feedback from healthcare providers and make process adjustments as needed.

https://www.biospace.com/article/u-s-regulators-announce-plans-for-monkeypox-antiviral-trial/

Eli Lilly To Shift To Commercial Sales Of Its Covid Antibody Drug

 As government orders dry up, the sales of bebtelovimab, which is currently authorized for emergency use, will target states, hospitals, and other health care providers. CNN notes other shifts in government covid policy are happening, with the CDC expected to ease covid guidelines, including for schools.

Eli Lilly & Co. said it plans to begin commercial sales of its Covid-19 monoclonal antibody treatment to states, hospitals and other healthcare providers this month, as the federal government’s supply of the drug is nearly depleted. The move marks a shift away from the way Lilly’s drug and most other Covid-19 treatments and vaccines have been distributed in the U.S. It will likely be the first test of whether the vaccines and treatments would remain accessible if shifted to a commercial market.

https://khn.org/morning-breakout/eli-lilly-to-shift-to-commercial-sales-of-its-covid-antibody-drug/

South Africa reports first death causally linked to COVID vaccine

 South Africa’s health regulator reported on Thursday a causal link between the death of an individual and Johnson & Johnson’s (J&J)  Covid-19 vaccine, the first time such a direct link has been made in the country.

The person presented with rare neurological disorder Guillain-Barre Syndrome soon after being given J&J’s vaccine, after which the person was put on a ventilator and later died, senior scientists told a news conference.

“At the time of illness no other cause for the Guillain-Barre Syndrome (GBS) could be identified,” Professor Hannelie Meyer said.

The person’s age and other personal details were not disclosed for confidentiality reasons.

Last July, US authorities added a warning to a factsheet for J&J’s vaccine saying data suggested there was an increased risk of GBS in the six weeks after vaccination. At the time it noted 100 preliminary reports of GBS in vaccine recipients, including 95 serious cases and one reported death.

J&J did not immediately respond to an emailed request for comment. The company said at the time of the US warning it was in discussions with regulators and the rate of reported cases of GBS in J&J vaccine recipients exceeded the background rate only slightly.

“The benefit of vaccination still far outweighs the risk,” Boitumelo Semete-Makokotlela, chief executive of the South African Health Products Regulatory Authority (SAHPRA), told reporters.

“In our context we have administered about 9 million (doses) of the Janssen (J&J) vaccine, and this is the first causally linked case of GBS.”

Europe’s medicines regulator last year added GBS as a possible side-effect of AstraZeneca’s Covid vaccine which, like J&J’s, uses viral vector technology.

South Africa’s Health Minister Joe Phaahla told Thursday’s news conference that as of mid-July there had been just over 6 200 “adverse events” reported to SAHPRA out of the more than 37 million Covid vaccine doses administered in the country, equivalent to 0.017%.

Semete-Makokotlela said the regulator had assessed around 160 deaths since the Covid vaccination rollout started but had not seen a causal link to vaccination until now.

South Africa has been using shots from J&J and Pfizer in its Covid vaccination campaign. The rollout got off to a slow start due to difficulties securing supplies and protracted negotiations with pharmaceutical companies, but more recently it has been slowed by hesitancy.

Around 46% of its adult population of 40 million is now fully vaccinated.

https://www.moneyweb.co.za/in-depth/own-your-life/sa-reports-first-death-causally-linked-to-covid-vaccine/

Patients seeking novel weight loss drugs find a ‘wild west’ of online prescribers

 Briana Lawson was ready to knock her diabetes into remission. For years, the 47-year-old health care consultant had treated her high blood sugar with metformin. But to avoid a lifetime of medication, she knew she’d need to lose weight. She’d tried fad diets, Weight Watchers, Nutrisystem, and had even considered surgery when the results didn’t stick. When she started reading about GLP-1 receptor agonists — which, last year, became the first new FDA-approved chronic weight management drug since 2014 — she was ready to give them a try.

“Once I was ready to consider the GLP-1s and did a lot of research,” said Lawson, “then I had to figure out, how do I get it?”

She didn’t have to look far. With enthusiasm for a new class of drugs has come dozens of telehealth companies ready to prescribe them. Online searches surfaced an ad for Found, a virtual weight loss coaching program that can be paired with a drug prescription for $149 a month. Another pointed to Calibrate, a $1,650, year-long online program that guarantees 10% weight loss with coaching and the prescription of an oral or injectable GLP-1, including Novo Nordisk’s recently-approved Wegovy.

Others ads tease quick prescriptions: “Weight Loss Shots Online – Rx After 15 min Dr. Consult,” one says. “$99 Weight Loss Pills Near You – No Diet or Exercise Required,” reads another.

Tens of thousands of people have gotten online scripts from telehealth companies. On the surface, that’s not a bad thing: Good weight loss support is hard to come by. But experts are growing deeply worried that the rise in direct-to-consumer platforms could harm patients. They see two causes for concern: First, that even well-intentioned companies that pair prescriptions with weight coaching aren’t designed to provide long-term support, leaving chronic disease patients in a lurch. And even more troubling, they say, are the platforms that have seemingly cropped up just to churn out prescriptions for a profit.

“The world of obesity and weight loss treatments and products have forever been a wild west,” said Scott Kahan, director of a weight management clinic in Washington, D.C. “While there’s a legitimate core of the field, far more that surrounds it is bogus and nonsense and predatory. And a lot of these telehealth companies, from what I’ve seen, are sort of toeing the line between them.”

Virtual weight loss platforms, obesity physicians acknowledge, are the product of a broken system. There are more than 100 million people in the United States with obesity, and only 5,000 specialists. At one Boston-based weight center, the wait list is 4,000 people long. Another is booking appointments out until November.

For patients who could benefit from anti-obesity medications, the path to a prescription can be truly odyssean. The shortage of specialists means most patients turn to their primary care office for help. But non-specialists can struggle to navigate a complex web of prescriptions, medication shortages, and insurance coverage for the many classes of weight management drugs.

“Telemedicine at least gives an opportunity to mitigate some of those access issues,” said Kahan.

Online companies dedicated to prescribing the drugs could offer an appealing option to get care without the stigma that’s all too common. “It is such a willpower and shame-focused industry,” said Sarah Jones Simmer, CEO of Found, which also offers a non-medication program. “PCPs are saying, ‘Just go lose weight and then come back. Try harder, eat less, exercise more.’”

For Lawson, her primary care doctor was never an option. “Absolutely not,” she said. “I don’t want to go and have that conversation. It doesn’t always go well when you’re like, ‘So, I’ve been on the internet.’” So she took out a loan to join Calibrate, and began taking a GLP-1, Ozempic, last month after a brief virtual appointment with one of its doctors. “The urge to snack, the urge to overeat, any of that, it immediately goes away,” she said. “I feel like this must be how ‘normal’ people relate to food, and it feels pretty freaking awesome.” In three weeks, she’s lost six pounds.

The proliferation of prescription-writing startups — many of which emphasize GLP-1s, if not prescribe them exclusively — mirrors the growing enthusiasm patients and some obesity doctors have expressed for the drugs, which were first designated to treat type 2 diabetes and can be prescribed off-label for weight management. “We were most excited about the way that it shifted consumer and doctor perception around medication for obesity treatment and medication for metabolic health more broadly,” said Calibrate CEO Isabelle Kenyon.

Calibrate’s business increased 20-fold after the FDA’s greenlight for Wegovy, and at least one startup, Sequence, was founded explicitly on the back of the drug’s approval. Their competitors’ business models vary widely, making money from a combination of coaching, insurance navigation, and clinician services, paid through subscriptions or one-off fees. Others profit directly from medication sales.

John Buse, an endocrinologist and former president for medicine and science at the American Diabetes Association, went from a BMI of 32 to 24 while on Wegovy, in line with the 15% weight loss clinical trial participants saw over 68 weeks. “It’s a miracle,” said Buse, who has received consulting fees and grants from GLP-1 manufacturers. “It was in a way so easy, you almost feel guilty about it.”

But that perception of a simple, guaranteed fix can pose a risk to vulnerable patients searching for solutions. The most dangerous and predatory online weight loss services, experts agree, are those that begin and end with a prescription.

Online ads and search results are often dominated by these types of services, frequently offered by telehealth sites that don’t focus exclusively on weight management. They tout same-day appointments, easy prescriptions, and the promise of losing weight easily without diet or exercise. “A lot of these [companies], unfortunately, hold the GLP-1s up and sort of dole them out like candy,” said Kahan.

Wegovy is only indicated for people with BMIs that fall in the obese category, or those with BMIs over 27 who have at least one other weight-related health issue, such as prediabetes or high cholesterol. Many virtual weight loss startups, including Calibrate, attempt due diligence before prescribing: asking patients a lengthy list of questions, conducting video intake visits, and ordering blood work to check for undiagnosed metabolic conditions before writing a prescription. And some companies emphasize that GLP-1s are a good fit for virtual prescribing because they have fewer side effects and contraindications than other weight management drugs.

But some services provide prescriptions based on nothing more than a glorified Google form, and without careful screening, patients could easily be handed medications that harm them. “When you create these conveyor belt treatment programs, I think that’s where you risk more blanket inappropriate care, or really stretching the bounds of what’s medically appropriate,” said Kahan. There are dangerous drug interactions with many weight management drugs. And experts said rapid online prescribing could put them in the hands of patients with histories of disordered eating.

Even when drugs are doled out more carefully, obesity experts question the underlying model of companies putting prescriptions front and center. Providers for online weight loss platforms that advertise prescriptions are less likely to discuss non-pharmaceutical alternatives with patients, which experts consider a best practice in obesity medicine.

“I think people should have access to all the options, or at least have all the options presented to them, in order for them to make an appropriate decision on what’s best for them,” said Angela Fitch, associate director of the Mass General Weight Center and president-elect of the Obesity Medicine Association.

That’s especially unlikely to happen when sites prescribe a single drug or drug class, or have a financial incentive to sell weight management products. Pharmaceutical manufacturer Currax runs a telemedicine platform that only prescribes its own drug, Contrave. Digital pharmacy Ro prescribes a single weight management product after buying up $30 million of the satiety-inducing capsule Plenity.

“When you have a hammer, everything looks like a nail,” said Kahan.

When she found Calibrate, Lawson was sold on the company’s combination of medication and coaching, which happens in 15-minute video visits every two weeks. “Their data is, GLP-1s can offer you this amount of weight loss, but if you do coaching with us, it creates this magical multiplier of potentially up to twice as much success,” said Lawson.

But the value of that support can vary widely between services, and with few virtual platforms specifying their coaches’ credentials and qualifications, it can be hard for patients to pick the right fit. “Different people have different needs for behavior change,” said Fitch. Some may do well with Found’s text-based coaching or Calibrate’s face-to-face accountability, while others want to pay for extra sleep therapy through the fee-for-service model of Mochi, another startup that launched in February.

For Lawson, Calibrate’s coaching strategy wasn’t a match, so she now pays even more for a personal trainer. “If I could just get the medication and drop the counseling now I would, but it’s not really an option, and I’m fearful of the interruption of medication availability,” she said. “You feel kind of suckered in.”

Lawson was also surprised when the doctor she saw didn’t discuss her diabetes before writing her prescription. And while she’s allowed to message or make appointments with a doctor if she wants, Calibrate doesn’t require her to see a clinician for the rest of the year — which is “kind of crazy,” Lawson said. Other startups similarly prioritize clinician visits at the beginning of their programs, some providing the ability to message doctors on a time delay through online portals.

“The medications are powerful, but require, to me, a lot more monitoring than can be done via coach,” said Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital.

Weight-loss startups emphasize that they’re not built to replace primary or urgent care. But to obesity specialists, frequent clinical follow-up is critical to make sure conditions intertwined with obesity — like heart disease risk, diabetes, and chronic joint pain — are improving, as well as to manage any side effects from the drugs. Many patients enroll in these programs without a primary care doctor who could fill that role, and establishing those lines of communication is recommended, but often not required.

That gap becomes especially critical as patients come to the end of their online programs, whether they’re pay-as-you-go or part of a year-long subscription. Once patients stop taking GLP-1s, they usually gain back the weight they’ve lost.

“[These companies] don’t really understand that it’s not a matter of, ‘Just take this drug for three months and lose the 50 pounds and you’re done,’” said Apovian. “They didn’t think down the line.”

Calibrate, for one, aims to build a path for members to transition off of medication; “long-term, chronic use of obesity medications would bankrupt the U.S. healthcare system,” a company spokesperson said. The company also says it passes prescriptions off when members leave the program, and transitions patients to other coaches when — as recently happened with the company’s layoffs of nearly a quarter of its staff — they lose access to a particular coach.

But some patients have grown so frustrated that they decided to leave the program, illuminating the risks of abruptly ending online care. Some are now seeking prescriptions from telehealth sites that provide no follow-up — the platforms that experts are most concerned about harming patients.

“I think it’s good people have access to treatment,” said Fitch. “I just hope it’s access that helps them treat long-term, not short-term.”

Obesity doctors expressed hope that over time, primary care physicians will become more comfortable with providing evidence-based obesity care — and that telemedicine in the right form can help patients gain access to both prescribing expertise and skilled follow-up care. “What I worry about is telemedicine that sits outside of the person’s normal care,” said Fitch, encouraging patients to try respectfully educating their primary care physician if they experience resistance.

And Buse counsels patience: With Wegovy’s approval still relatively recent, “your PCP isn’t very far behind the times,” he said. With the anticipated approval of another GLP-1 for weight management this year, he thinks it will soon be easier for patients to get evidence-based care that can be so difficult to find. Telemedicine has the potential to drive improved access, too — but only if it prioritizes patients over profits.

https://www.statnews.com/2022/08/04/weight-loss-drugs-telehealth-calibrate-found/