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Saturday, April 2, 2022

Pentagon Clarifies No 'Offensive' Bioweapons At US-Linked Ukraine Labs

 by Dave DeCamp via AntiWar.com, 

A Pentagon official told Congress on Friday that there are no "offensive" biological weapons in any of the dozens of US-linked labs in Ukraine.

"I can say to you unequivocally there are no offensive biologic weapons in the Ukraine laboratories that the United States has been involved with," Deborah Rosenbaum, the assistant secretary of defense for nuclear, chemical, and biological defense programs, told the House Armed Services subcommittee.

The Pentagon funds labs in Ukraine through its Defense Threat Reduction Agency (DTRA). According to a Pentagon fact sheet released last month, since 2005, the US has "invested" $200 million in "supporting 46 Ukrainian laboratories, health facilities, and diagnostic sites."

Moscow has accused Ukraine of conducting an emergency clean-up of a secret Pentagon-funded biological weapons program when Russia invaded. The World Health Organization said it advised Ukraine to destroy "high-threat pathogens" around the time of the invasion.

For their part, the US maintains that the program in Ukraine and other former Soviet states is meant to reduce the threat of biological weapons left over from the Soviet Union. While downplaying the threat of the labs, Pentagon officials have also warned that they could still contain Soviet-era bioweapons.

Robert Pope, the director of the DTRA’s Cooperative Threat Reduction Program, told the Bulletin of the Atomic Scientists in February that the labs might contain Soviet bioweapons and warned that the fighting in Ukraine could lead to the release of a dangerous pathogen.

The Biden administration has tried to portray any concerns about the labs as "Russian propaganda." When the issue gained more media attention, Biden officials started accusing Moscow of plotting to use chemical or biological weapons, but the US hasn’t presented any evidence to back up its claims.

https://www.zerohedge.com/geopolitical/pentagon-says-pathogens-us-linked-ukraine-labs-not-offensive-bioweapons

Most Chinese Biotech Stocks Can Continue US Listing After New Audit Framework

 

  • According to a Bloomberg report, U.S. regulators could reportedly have full access to auditing reports from most of the 200-plus China-based companies listed in New York in mid-2022.

  • In the drafting stage, the framework from the China Securities Regulatory Commission and other national agencies would let most Chinese firms keep their U.S. listings, Bloomberg said, citing anonymous sources. But those that hold sensitive data could still be delisted.

  • Nearly 300 companies are on the SEC's initial list of those at risk of falling off the Nasdaq, including four biopharma stocks, BeiGene Ltd (NASDAQ: BGNE), Hutchmed China Ltd (NASDAQ: HCM), Zai Lab Ltd (NASDAQ: ZLAB) and CASI Pharmaceuticals Inc (NASDAQ: CASI).

  • If the plan proceeds, non-compliant businesses will be kicked off the New York Stock Exchange and Nasdaq in 2024.

  • In a move to come into compliance, Hutchmed said this week it would assess "the merits of appointing an auditor outside of China." Zai Lab said it plans to review its audit process, as well.

  • Earlier Friday, CASI said it will evaluate options, "which include but are not limited to adding business processes and control to meet the requirements of the HFCAA."

Biotech Investors: Mark Your Calendar For April PDUFA Dates

 Biopharma stocks are sensitive to a key binary event called the PDUFA date, the date by which the Food and Drug Administration is required to give its verdict on a regulatory application filed with it.

The month of March saw several approvals coming through, while outright rejection and postponements were few and far between. Three new molecular entities, or NMEs, were approved during the month. NMEs are drugs that contain active moieties that haven't been previously approved by the FDA. It's, therefore, an indicator of innovation in drug research.

Marinus Pharmaceuticals, Inc.'s (NASDAQ:MRNS) Ztalmy, indicated to treat seizures associated with a rare genetic condition known as CDKL-5 deficiency disorder (CDD), was among the NMEs that scored win the FDA in March. H.C. Wainwright analyst Douglas Tsao expects peak U.S. sales potential of $92 million for Ztalmy, given CDD is a relatively small market.

Other NMEs approved during the month included Bristol-Myers Squibb Company's (NYSE:BMY) melanoma combo therapy Opdualag and Novartis AG's (NYSE:NVS) Pluvicto for treating a certain type of advanced, castration-resistant prostate cancer.

On the flip side, Akebia Therapeutics, Inc.'s (NASDAQ:AKBA) vadadustat was rejected by the FDA as a treatment option for anemia in chronic kidney disease patients.

Here are the key PDUFA dates scheduled for April.

Can BioXCel Push Psychiatric Disorder-Associated Agitation Drug Past Finish Line?

  • Company: BioXcel Therapeutics, Inc. (NASDAQ:BTAI)
  • Type of Application: new drug application
  • Candidate: dexmedetomidine (BXCL501)
  • Indication: agitation associated with schizophrenia and bipolar disorders I and II.
  • Date: April 5

BXCL501 is an investigational, proprietary, orally dissolving thin film formulation of dexmedetomidine for the treatment of agitation associated with neuropsychiatric disorders. The original PDUFA date of Jan. 5, 2022 was pushed back by three months, with BoXcel communicating that the FDA needed three more months to review data pertaining to analyses of clinical data submitted by the company upon the regulator's information request.

Regeneron Awaits Approval Of Antibody Cocktail For Prophylactic Treatment Of COVID-19

  • Company: Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN)
  • Type of Application: BLA
  • Candidate: REGEN-COV
  • Indication: prophylactic treatment of COVID-19
  • Date: April 13

Regeneron's REGEN-COV is a cocktail of two monoclonal antibodies, namely casirivimab and imdevimab, that's designed to block infectivity of SARS-CoV-2 using the company's proprietary VeloImmune and VelociSuite technologies. The biopharma has a collaboration agreement with Roche Holding AG (OTC:RHHBY) for increasing global supply.

Alnylam Hopes To Get Clearance For Second RNAi Therapeutic For ATTR Amyloidosis

  • Company: Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY)
  • Type of Application: NDA
  • Candidate: Vutrisiran
  • Indication: polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) polyneuropathy
  • Date: April 14

Vutrisiran is an investigational RNAi therapeutic being evaluated for treating hATTR in adults. hATTR is an inherited, progressively debilitating and fatal disease caused by mutations in the TTR gene, which will cause the build up of amyloid protein in organs and tissues. Vutrisiran is a second-generation, subcutaneous formulation of Alnylam's Onpattro, which was approved for the same indication. Onpattro is administered intravenously.

No or no-go For Amneal's Avastin Biosimilar

  • Company: Amneal Pharmaceuticals, Inc. (NYSE:AMRX)
  • Type of Application: BLA
  • Candidate: Bevacizumab
  • Indication: colorectal cancer
  • Date: April 17

Amneal's Bevacizumab regulatory application was accepted for standard review pursuant to Section 351(k) pathway of the Public Health Service Act, to the Biosimilar User Fee Act. The biosimilar was developed in collaboration with mAbxience, a Spain-based biotechnology company. Bevacizumab is the biosimilar version of Roche's Genentech unit's Avastin. Upon approval, the company expects to market it under the proprietary name Alymsys.

Bevacizumab is a vascular endothelial growth factor inhibitor. Amneal is seeking approval for Bevacizumab for the treatment of metastatic colorectal cancer. According to IQVI, U.S. annual sales for Bevacizumab for the 12 months ended April 2021 were approximately $2.8 billion.

Bristol-Myers Squibb Hopes For No Further Heartache On Heart Disease Drug

  • Company: Bristol-Myers Squibb Company (NYSE:BMY) & LianBio (NASDAQ:LIAN)
  • Type of Application: NDA
  • Candidate: mavacamten
  • Indication: symptomatic obstructive hypertrophic cardiomyopathy (oHCM)
  • Date: April 28

Mavacamten is a cardiac myosin inhibitor that demonstrated clinically meaningful improvements in symptoms, functional status, and quality of life in symptomatic oHCM patients in a pivotal trial. The investigational therapy came into Bristol-Myers Squibb's stable through its Myokardia acquisition. Myokardia and LianBio initially collaborated to develop mavacamten.

HCM is a chronic, progressive disease characterized by the abnormal thickening of heart muscle, which makes it difficult for the heart to pump blood. It affects one in every 500 persons and can lead to cardiac dysfunction and other debilitating symptoms.

In November, the company communicated an extension to the review period for mavacamten, and gave a new PDUFA date of April 28.

Can Supernus Snag Label Expansion For ADHD Drug?

  • Company: Supernus Pharmaceuticals, Inc. (NASDAQ:SUPN)
  • Type of Application: supplemental NDA
  • Candidate: Qelbree (viloxazine extended-release capsules)
  • Indication: attention deficit hyperactivity disorder
  • Date: April 29

Qelbree received its first approval in April 2021 for treating ADHD in pediatric patients, ages six to 17 years. The company now expects to make the treatment available to adult patients, who according to the company number around 10 million in the U.S.

Chinese Biopharma Hutchmed Knocks FDA Door For Approval Of Neuroendocrine Tumor Treatment Candidate

  • Company: HUTCHMED (China) Limited (NASDAQ:HCM)
  • Type of Application: NDA
  • Candidate: surufatinib
  • Indication: pancreatic and extra-pancreatic neuroendocrine tumors (NET)
  • Date: April 30

Hutchmed's surufatinib is marketed in China under the brand name Sulanda. Surufatinib is evaluated as a treatment option for NET, which forms in cells interacting with the nervous system or in glands that produce hormones. It originates mostly in the gut and lungs and can be benign or malignant.

Will Axsome Add A Drug To Crowded Migraine Market?

  • Company: Axsome Therapeutics, Inc. (NASDAQ:AXSM)
  • Type of Application: NDA
  • Candidate: meloxicam-rizatriptan (AXS-007)
  • Indication: acute migraine
  • Date: April 30

AXS-07 (MoSEIC meloxicam-rizatriptan) is an oral, rapidly absorbed, multi-mechanistic, investigational medicine for migraine. According to CDC, over 37 million Americans suffer from migraine.

AXS-007, if approved, will be joining a crowded field, comprising AbbVie, Inc. (NYSE:ABBV), Eli Lilly & Company (NYSE:LLY) and Biohaven Holding Company Limited (NYSE:BHVN).

Coherus, Chinese Partner Seek Approval For Nasopharyngeal Cancer Treatment

  • Company: Coherus BioSciences, Inc. (NASDAQ:CHRS)
  • Type of Application: BLA
  • Candidate: Toripalimab
  • Indication: nasopharyngeal caner
  • Date: April 30

Coherus is developing toripalimab, an anti PD-1 monoclonal antibody, along with China's Junshi Biosciences. The investigational treatment is being evaluated in combination with gemcitabine and cisplatin for the first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma and toripalimab monotherapy for the second-line or above treatment of recurrent or metastatic NPC after platinum-containing chemotherapy.

Adcom Calendar

FDA's Oncologic Drugs Advisory Committee is scheduled to meet on April 22 to discuss TG Therapeutics, Inc.'s (NASDAQ:TGTX) sNDA for Ukoniq (umbralisib) tablets, and BLA for ublituximab injection. The proposed indication for these two products is in combination for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

The committee will also discuss the existing umbralisib indications in patients with relapsed or refractory follicular lymphoma and marginal zone lymphoma approved under accelerated approval regulations.

https://markets.businessinsider.com/news/stocks/attention-biotech-investors-mark-your-calendar-for-april-pdufa-dates-1031327374

Pharmacists Get More Leeway to Offer Treatment With Testing

 When Reyna or Justin Ansley or one of their three kids feels sick and needs to be tested for strep throat or flu, there's a good chance they'll head to their local pharmacy in Hemingford or Alliance, Nebraska. Dave Randolph, the proprietor of both locations of Dave's Pharmacy, can do a rapid test, give them medicine if they need it, and send them on their way.

"I'm a cattle rancher," said Reyna Ansley, whose family lives about 15 miles outside Hemingford. "You don't necessarily have the time to drive to the doctor and sit in the waiting room. It's really quicker through Dave."

The Ansleys don't have health insurance and using the pharmacy, where Randolph charges $50 to $60 to do the tests, is cheaper than paying up to $200 for an office visit with a local doctor, Ansley said. If the test is positive, the medications generally cost $20 to $30.

Randolph's ability to provide treatments for flu and strep throat is somewhat unusual. He can do so in Nebraska because he has an annual collaborative practice agreement with a local doctor that is subject to state approval.

The easy availability of pharmacists also helped propel them into a key role during the pandemic as they became a go-to resource for covid-19 testing and vaccines. Yet even before covid engulfed the country, many states were giving pharmacists a bigger role in consumers' health.

According to the National Alliance of State Pharmacy Associations, more than a dozen states have expanded what pharmacists can do to include testing and treating people for illnesses such as strep throat, flu, and urinary tract infections and preventing HIV. Some states allow pharmacists to prescribe oral contraceptives or drugs to help people quit smoking. Typically, pharmacists have prescribing authority under agreements with doctors or rules called statewide protocols.

But a limited number of states have gone further, allowing pharmacists to prescribe medications on their own to treat a broad range of conditions for which there are rapid point-of-care tests, if it's appropriate based on clinical guidelines.

"We're seeing more states looking at direct prescribing authority now as opposed to collaborative practice agreements," said Allie Jo Shipman, director of state policy at the National Alliance of State Pharmacy Associations. The alliance offers point-of-care testing and point-of-care treating training programs for pharmacists and pharmacy students.

The Biden administration, which has leaned on pharmacies to help battle the covid pandemic by administering vaccines and tests, is now calling for a limited number of pharmacies with retail clinics that employ doctors or other health care workers with prescribing authority to directly provide medication rapidly to people who test positive for the virus. The "test-to-treat" program is designed to make sure that people with covid get a course of antiviral medication quickly because it is most effective if used within five days of when someone shows symptoms.

Pharmacists say their expanded efforts on covid have helped raise their profile.

"One of the big things that came out of covid is that consumers understand that pharmacies do offer these services that are high-quality and convenient and support their health," said B. Douglas Hoey, CEO of the National Community Pharmacists Association, which represents the interests of independent pharmacists.

But physicians don't necessarily welcome this development. Doctor groups have long objected to the taking on of certain types of patient care by pharmacists, nurse practitioners, physician assistants, and other nondoctors unless it is overseen by or approved by physicians.

In November, the American Medical Association, which represents doctors, announced that since 2019, it had successfully opposed more than 100 legislative actions that would have expanded nonphysicians' scope of practice, called scope creep. The group also issued a statement criticizing the Biden administration's plan to allow pharmacy-based clinics to prescribe covid antiviral medications, saying that the program poses a danger to patient safety and risks negative health outcomes. And the AMA unsuccessfully opposed a federal decision to let pharmacists give covid vaccines to children younger than 18.

Meanwhile, the American College of Physicians, which represents internists, announced it "opposes independent pharmacist prescriptive privileges and initiation of drug therapy outside of a collective practice agreement, physician standing order or supervision, or similar arrangement."

The AMA didn't respond to questions about independent pharmacist prescribing, and the ACP declined to comment on its policy.

But are physicians correct that patient safety is at risk if a doctor isn't involved in prescribing decisions? Pharmacists say that they want to provide care in line with their training and skills and that they know their limits. And they note that timely prescribing is vital for treating covid and other infectious diseases.

They also note that pharmacists are increasingly part of the multidisciplinary clinical teams that direct patient care at hospitals and in health care systems.

"Pharmacists are the professionals that are the most trained to deal with drug interactions," said Rita Jew, a pharmacist who is president of the Institute for Safe Medication Practices, a nonprofit that focuses on preventing medication errors. "We monitor patients for both efficacy and side effects. So from that perspective, it's not a safety concern. Delay in treatment is a concern."

Many pharmacists are eager to expand their menu of patient services, but payment remains a problem. Pharmacists aren't generally recognized as service providers under Medicare and don't typically receive payment when they spend time evaluating, testing, or treating patients. Many private insurers follow Medicare's lead on payment.

For many people, pharmacies are convenient and familiar. More than 90% of people in the United States live within 5 miles of a community pharmacy, and Medicare beneficiaries visit the pharmacy nearly twice as often as they do their primary care physician.

Dr. Jeffrey Singer, a general surgeon and a senior fellow at the libertarian Cato Institute, wrote a recent blog post suggesting that doctors who object to nonphysician prescribing may be more worried about competition than patient safety.

"Rather than work to prevent laws that could meet the needs of patients, the onus is on the profession to persuade people that they need to see a doctor," Singer said in an interview, adding that he has relied on pharmacists' expertise in his practice. "I ask them, 'Is there any particular problem with this drug?' They have the software. And that's what they're trained to do."

In Arkansas, a 2021 law gave pharmacists the authority to treat conditions for which there are point-of-care tests, as long as they follow statewide protocols established by the state board of pharmacy and the state medical board.

"There are myriad tests that are on the market now that are quick and inexpensive and that can really increase access dramatically for folks who don't have time or resources to go to a primary care provider," said Scott Pace, a pharmacist and co-owner of Kavanaugh Pharmacy in Little Rock, Arkansas.

But pharmacists aren't interested in replacing physicians, said Shipman. "We want to come alongside physicians," she said. "We want to be another health care provider. In the middle of the pandemic, we need more help. The burden is too great to be carried by any one provider."

https://www.medscape.com/viewarticle/971418

In-Person ACC Meeting Returns, Serving Diet Intervention Studies and More

 Much-anticipated data on salt restriction and nutrition education are on the menu at this weekend's American College of Cardiology (ACC) meeting, which welcomes in-person attendees for the first time since the start of the COVID-19 pandemic.

The meeting will take place in Washington, D.C., and will also offer virtual streaming and participation for some sessions.

Among ACC's late-breaking scientific presentations scheduled for Saturday is SODIUM-HF, the largest and longest-running randomized trial of salt restriction in patients with heart failure. If nutritional counseling reduces sodium intake and cuts down on major adverse events or hospitalizations at 1 year, SODIUM-HF could be the study that strengthens the limited evidence base for curbing dietary salt.

Primary prevention guidelines currently recommend limiting salt, but do not endorse a specific target daily amount.

Also notable at this year's ACC meeting is the SuperWIN trial, which tested how nutrition education sessions in grocery stores, coupled with online tools, might help people adhere to the heart-healthy Dietary Approaches to Stop Hypertension (DASH) diet. A partnership with the Kroger supermarket chain allowed researchers to determine how participants' eating habits changed after 3 months based on their grocery purchasing data. SuperWIN will be presented on Sunday in a late-breaking trial session.

Other highlights of the scientific program include:

  • VALOR-HCM: A phase III trial evaluating mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy; topline results were previously announced, with the cardiac myosin inhibitor reportedly cutting down the need for septal reduction therapy at week 16
  • POISE-3: In this large trial, tranexamic acid is put to the test for bleeding prevention in noncardiac surgery

  • PROTECT: Also in the setting of noncardiac surgery, this study looked at intraoperative hypothermia versus aggressive warming to 98.6º F to find which is associated with less myocardial injury at 30 days

  • CHAP: In this randomized trial, pregnant women with chronic hypertension are treated with a blood pressure target goal of 140/90 mm Hg, with pregnancy outcomes compared against untreated controls

  • PROMPT: A cluster-randomized trial on using electronic health record alerts to improve prescribing of guideline-directed medical therapy for heart failure
  • TRANSLATE-TIMI 70: A dose-finding study evaluating the lipid-lowering effects of vupanorsen, an antisense oligonucleotide inhibiting ANGPTL3 synthesis

  • FLAVOUR: A head-to-head comparison of fractional flow reserve versus intravascular ultrasound to guide angioplasty in people with intermediate coronary stenosis

On Friday, the eve of the ACC meeting's kickoff, updated heart failure guidelines will be released. A Saturday session will be dedicated to the new recommendations.

The conference comes during a time when states across the U.S. are relaxing their pandemic restrictions, despite the spread of the Omicron subvariant BA.2.

For a safe return to an in-person meeting experience, ACC organizers are requiring attendees to provide proof of full COVID vaccination (booster optional), which will be verified when they pass one of four physical health and safety checkpoints. Additionally, masks must be worn in the convention center.

https://www.medpagetoday.com/meetingcoverage/acc/97974

Mix and Match mRNA Boosters May Be a Good Idea

 The two mRNA vaccines authorized in the U.S. prompt different immune responses -- and that could suggest a benefit for mixing and matching booster shots, researchers said.

Galit Alter, PhD, of Harvard Medical School in Boston, and colleagues set out to investigate the immune responses driven by three doses of Pfizer or Moderna in a cohort of 73 healthcare workers. Both vaccines induced robust functional humoral immune responses, but there were clear differences, they reported in a paper in Science Translational Medicine.

Moderna appeared to have an advantage in mucosal immunity, as measured by immunoglobulin (Ig) A, while Pfizer had a "really functional IgG response," Alter told MedPage Today.

"The mRNA vaccines are inducing different flavors of immunity," Alter said. "That suggests the immune system is seeing them in slightly different ways. And we know that 'different' is incredibly important for training the immune system."

Clinicians on medtwitter quickly interpreted the findings as supporting mixing and matching mRNA boosters -- a strategy that may become even more relevant as certain groups are now eligible for second boosters.

While that wasn't the intention of the study, Alter said it was a "creative" response and agreed that heterologous boosting could be advantageous, based on these findings.

"By slightly changing the way that the immune system sees the COVID antigen, we could essentially not only improve the overall quality and levels of the antibodies we induce, like the amount of neutralizing antibodies, but it could give us better mucosal immunity, or better affinity maturation," Alter said.

In their study of healthcare workers -- 28 received Moderna and 45 had Pfizer -- Alter and colleagues found that those who received Moderna had higher concentrations of IgA binding titers targeting the receptor binding domain (RBD) and the N-terminal domain (NTD). They also had higher levels of antibodies that elicit neutrophil phagocytosis and natural killer cell activation.

When looking specifically at variants of concern, they again found similarly robust functional antibody responses, but vaccination with Pfizer was associated with an IgM- and IgG-biased profile, whereas Moderna prompted an IgA- and IgG-driven profile, they reported.

Alter and colleagues noted that there's an "emerging appreciation" of the importance of antibody functions aside from neutralization, especially with the rise of new variants. Mutations can affect specific regions on the spike protein targeted by neutralizing antibodies, but functional antibodies can target the whole surface of the spike protein, and thus aren't compromised in the same way.

Earlier data have suggested that mixing and matching vaccines was safe and induced robust immune responses, said Christine Johnston, MD, MPH, of the University of Washington School of Medicine in Seattle, who was involved in an NIH-funded study of various boosting strategies published in the New England Journal of Medicine. That study supported an FDA recommendation in October allowing for mixing and matching boosters.

"It makes sense ... that if you're stimulating slightly different parts of the immune system, you would get better overall coverage from the version of SARS-CoV-2 that's circulating, or from variants that are emerging," Johnston said of the interpretations of Alter's data.

While Moderna "looks a little bit better for IgA," or mucosal immunity, Johnston said, she warned that "we don't know the real correlate of immunity -- the overall profile of immune response that's going to give us the best protection against infection or severe disease."

Because that correlate is still unknown, Alter said, "I think the suggestion [of mixing and matching mRNA vaccines] is brilliant, to get the best of both."

"You can diversify your immune response as much as possible to get maximal protective immunity," Alter said. "And then one day when we have the mechanistic correlate of protection, we'll be able to design vaccines that specifically give you that response."

Johnston said studies are ongoing to determine whether mixing and matching various vaccines can lead to clinical benefit, though these will never be at the same scale as the initial vaccine trials. "It's going to be a hard question to answer," she said.

Robert Schooley, MD, of the University of California San Diego, noted that both mRNA vaccines are "highly efficacious" and that any difference in immune profile, "if real, is not sufficiently great to make a recommendation of one over the other."

"If someone is in line for a booster vaccination," Schooley said, "the vaccines are so similar in efficacy that it would be a mistake to delay being vaccinated with whichever of the two is available."


Primary Source

Substance Use Disorder Symptoms Follow Teens Into Adulthood

 Adolescents with substance use disorder (SUD) were more likely to have subsequent prescription drug use and symptoms of SUD in adulthood, revealed a longitudinal analysis that followed high school seniors to the age of 50.

Students with two or more SUD symptoms at age 18 had higher odds of medical prescription drug use and prescription drug misuse in adulthood, and 61.6% of adolescents with the most severe SUD symptoms (six or more) had at least two SUD symptoms in adulthood, reported Sean Esteban McCabe, PhD, of the University of Michigan in Ann Arbor, and colleagues.

"This finding reinforces that the long-term sequelae are more deleterious for those with more severe SUD symptoms during adolescence," the study group wrote in JAMA Network Open. "Notably, most adolescents with severe SUD symptoms do not mature out of symptomatic substance use during the transition from adolescence to adulthood."

Writing in an accompanying commentary, Nora Volkow, MD, and Eric Wargo, PhD, of the National Institute on Drug Abuse in North Bethesda, Maryland, said: "Critics of the chronic disease model of addiction have argued that people frequently recover on their own, unaided, from SUDs, but [McCabe and colleagues] show that SUDs in adolescence often carry over into adulthood and may last decades."

"Consequently, screening in this age group could be leveraged to help estimate adult SUD and the risk of adverse health outcomes, including overdoses," Volkow and Wargo added.

In 2020, the U.S. Preventive Services Task Force recommended drug screenings for adults, but said that evidence on the benefit of drug screening adolescents was insufficient.

McCabe and co-authors said their study was the first national investigation to examine the long-term association of SUD symptoms in adolescence with prescription drug use, prescription drug misuse, and SUD symptoms in adulthood.

Using multivariable analysis, the team found that adolescents with the highest SUD symptom severity were one and a half times more likely to use prescription drugs in adulthood compared with those without SUD symptoms in adolescence (adjusted odds ratio 1.55, 95% CI 1.11-2.16).

Adolescents with four or more SUD symptoms were nearly twice as likely to have prescription drug misuse in the past year as adults compared with those without SUD symptoms in adolescence, the researchers added.

Notably, while SUD symptoms decreased overall between ages 35 and 50, prescription drug use and misuse increased in that same age group, McCabe and co-authors said. In addition, approximately half the adults prescribed opioids, sedatives, or tranquilizers had reported two or more SUD symptoms at age 18.

"Prescribers should be aware that many adults prescribed opioids, sedatives, or tranquilizers had multiple SUD symptoms during adolescence and require careful assessment and monitoring," the researchers wrote. "Importantly, the cohorts of adolescents who were high school seniors between 1976 to 1986 and were followed over the 32-year study time frame (ending 2018) [run] parallel to the emergence and steep increase in the opioid crisis, largely associated with the widespread overprescribing of opioids."

"These prescribing practices may be associated with the high rates of prescription drug use and PDM [prescription drug misuse] as these cohorts aged into middle adulthood," the team added. "Although the association between adolescent SUD symptom severity and adult prescription drug use and PDM would still stand, it is important to acknowledge that the opioid crisis has led to changes in prescribing practices over the past several years that warrant more research that reexamines these associations over time."

The multi-cohort Monitoring the Future study used questionnaires to assess SUD symptoms over a 32-year period from ages 18 (when participants were high school seniors) to 50, beginning in 1975. Enrollees participated in 10 follow-up surveys in that period, and the baseline response rates ranged from 77% to 84% over the study period.

This analysis included 5,317 respondents, of whom 51.2% were women and 77.9% were white. One-fifth of respondents reported having two to three SUD symptoms, 12% reported four to five, and 11.5% reported six or more SUD symptoms at baseline.

The researchers acknowledged that school dropouts and institutionalized populations, who have higher rates of severe SUD symptoms, were excluded from the study, which may have resulted in underestimates. In addition, Volkow and Wargo noted that prescription stimulant use and smoking history were not studied.


Disclosures

The study was supported in part by grants from the National Institute on Drug Abuse (NIDA).

McCabe and co-authors reported no conflict of interest disclosures.

Volkow reported being the Director of the NIDA; Wargo reported no disclosures.