Author: admin

Patients who discontinue dupilumab treatment after their atopic dermatitis has cleared remain susceptible to relapse and thereby require longer-term management and monitoring, according to a new study.¹ Several independent risk factors are implicated in the greater risk of disease recurrence following treatment discontinuation, the authors explained in Frontiers in Medicine.

“Dupilumab controls symptoms while in use, but relapses may occur after discontinuation of use,” they wrote. “How to choose the most appropriate treatment regimen for different populations, which can ensure sustained efficacy while minimizing the probability of disease recurrence, and thus reduce the burden of disease on patients has become a key issue that needs to be urgently resolved.”

There were 141 patients with atopic dermatitis included in this analysis, who received care at the dermatology outpatient clinic at Sichuan Provincial People’s Hospital in Chengdu, China, between January 1, 2021, and December 31, 2023. The latter date was the cohort termination time, and patients were followed retrospectively from medication discontinuation until disease recurrence or the study end date. These follow-ups were every 2 weeks.

Patients’ mean (SD) age was 37.3 (20.7) years, and 42.6% were female patients. To be included, they had to have been treated with dupilumab for at least 4 weeks, received the standard induction dose of dupilumab (600 mg for body weight ≥ 30 kg; 300 mg for body weight < 30 kg), received the standard maintenance dose of dupilumab (300 mg every 2 weeks for body weight ≥ 30 kg; 300 mg every 2 weeks for body weight < 30 kg), and have complete medical records and follow-up information.

Overall, the investigators saw a recurrence rate of 23.4% (95% CI, 16%-30%) and a median time to relapse of 29 weeks (range, 22-59). No patient deaths were attributed to recurrence of atopic dermatitis, but 1 patient death was reported during the follow-up period, and this was linked to serious complications.

The highest risks of recurrence were seen in patients who had comorbid conjunctivitis (HR, 7.912; 95% CI, 1.280-48.895; P = .026), were treated with dupilumab for fewer than 16 weeks (HR, 5.871; 95% CI, 2.154-16.003; P = .001), had a body mass index (BMI) of 28 kg/m² (HR, 5.653; 95% CI, 2.331-13.713; P < .001), were male (HR, 5.634; 95% CI, 1.727-18.373; P = .004), and had a familial predisposition to allergy (HR, 3.438; 95% CI, 1.351-8.747; P = .01).

Risk factors that did not reach statistical significance were having comorbid urticaria (HR, 1.035) or comorbid allergic rhinitis (HR, 1.023), despite their noted modestly increased risks of atopic dermatitis recurrence. Factors that were negatively associated with risk of recurrence were comorbid asthma (HR, 0.935), previous corticosteroid treatment (HR, 0.880), age older than 60 (HR, 0.763), disease duration of 10 or more years (HR, 0.761), and comorbid chronic bronchitis (HR, 0.416).

Explaining the strengths of their findings, the study investigators highlighted several examples of where their results echoed previous research on links between risk factors and atopic dermatitis recurrence. There was a greater risk of reduced drug survival during dupilumab treatment in a setting that included male sex (HR, 2.34; 95% CI, 1.14-4.78; P = .02) and susceptibility to allergic rhinitis (HR, 2.61; 95% CI, 1.37-5.00; P = .004).² Another previous study showed male sex (P = .002) and high BMI (P < .000) to be potential determinants of atopic dermatitis severity. Also, several other studies have demonstrated that female gender and a BMI below 24 kg/m² may predispose individuals to better responses to dupilumab.^3-5

The investigators expressed their concern both for the lack of early intervention in the setting of atopic dermatitis relapse and for the disease status of these patients, and they noted that subsequent management and treatment in this setting should encompass reassessment, potential dupilumab reinitiation, and transitioning to another treatment regimen if needed. However, they also add that their results show how dupilumab maintained its effectiveness when reinitiated in their study population, that this treatment course was effective in older and younger patients—which reflects a real-world population, and that they believe these data reflect “modifiable factors leading to [atopic dermatitis] relapse and provide insight into the risk profiles associated with relapse at different stages of disease.”

References

1. Chen M, Wen X, Liu J, et al. Recurrence and influencing factors of moderate-to-severe atopic dermatitis after dupilumab withdrawal: a retrospective cohort analysis. Front Med (Lausanne). 2025:12:1585368. doi:10.3389/fmed.2025.1585368
2. Wollenberg A, Ariens L, Thurau S, van Luijk C, Seegräber M, de Bruin-Weller M. Conjunctivitis occurring in atopic dermatitis patients treated with dupilumab–clinical characteristics and treatment. J Allergy Clin Immunol Pract. 2018;6(5):1778-1780.e1. doi:10.1016/j.jaip.2018.01.034
3. Gu C, Wu Y, Luo Y, et al. Real-world efficacy and safety of dupilumab in Chinese patients with atopic dermatitis: a single-centre, prospective, open-label study. J Eur Acad Dermatol Venereol. 2022;36(7):1064-1073. doi:10.1111/jdv.18109
4. Stingeni L, Bianchi L, Antonelli E, et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: a multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022;36(8):1292-1299. doi:10.1111/jdv.18141
5. Mastorino L, Richiardi I, Gelato F, et al. Predisposition to conjunctivitis and male sex reduces drug survival of dupilumab in adults and adolescents. Expert Opin Biol Ther. 2024;24(8):863-868. doi:10.1080/14712598.2024.2372367

Contaminated metal at an industrial site in Indonesia may be the source of radioactive material that led to massive recalls of imported frozen shrimp, international nuclear safety officials say, as efforts are underway to halt more U.S.-bound shipments.

The International Atomic Energy Agency said Friday that officials are in “constant contact” with Indonesian nuclear regulators who have detected Cesium-137, a radioactive isotope, at a processing plant that sent millions of pounds of shrimp to the U.S.

“Preliminary information suggests that it may have originated from activities at a metal melting facility at the same industrial site or from the disposal of scrap metal junk to other areas of the site,” IAEA spokesperson Fredrik Dahl said in an email.

No U.S. investigators have been sent to the site in Serang, west of Jakarta, federal officials said.

Meanwhile, the company that exported the shrimp, PT Bahari Makmur Sejati, also known as BMS Foods, has recalled more than 300 shipping containers that were already on their way to the U.S., Dahl said.

The U.S. Food and Drug Administration warned last month that Cesium-137 was detected in shipping containers sent to four U.S. ports, and in a sample of imported frozen shrimp. That spurred multiple recalls of shrimp sold at Walmart, Kroger and other stores.

This week, additional recalls were issued by Tampa Maid Foods LLC, of Florida, for breaded butterfly shrimp sold under Admiral of the Fleet, Portico Seafood Classic and other labels.

None of the shrimp that triggered alerts or tested positive for Cesium-137 was released for sale, the FDA said. But other shipments sent to stores may have been manufactured under conditions that allowed the products to become contaminated, the agency said.

The risk appears to be small, but the shrimp could pose a “potential health concern” for people exposed to low levels of Cesium-137 over time, FDA officials said.

The FDA issued an import alert for shrimp from BMS Foods to stop the products from coming into the U.S.

The company sent about 12 million pounds of shrimp to U.S. ports in Los Angeles, Houston, Miami and Savannah, Georgia, in July and August, according to U.S. Customs and Border Protection records obtained by Import Genius, a trade data analysis company.

CPB officials alerted the FDA to potential radioactive contamination of multiple shipping containers. The National Nuclear Security Administration has sent emergency teams on “multiple deployments” to “isolate and characterize the extent of Cesium-137 contamination,” a U.S. Energy Department spokesperson said.

The level of Cesium-137 detected in the frozen shrimp was about 68 becquerels per kilogram, a measure of radioactivity. That is far below the FDA’s level of 1,200 becquerels per kilogram that could trigger the need for health protections.

Still, it is unusual to see that concentration of Cesium-137 in shrimp, said Steve Biegalski, a nuclear medicine expert at the Georgia Institute of Technology.

It’s possible that the contamination could have come from recycling old medical equipment that contained Cesium-137, Biegalski said. The material has been used in medical devices to reduce blood contamination and to treat cancer, for instance.

When such equipment is no longer useful, it can be recycled. But if the Cesium-137 isn’t properly removed, radioactive material can be released into the environment.

“If they get broken up in some sort of crushing mechanism, then all of a sudden, it’s basically a salt,” Biegalski said. “It would be like you taking a giant salt shaker and spreading it all over the kitchen floor.”

Containing the contamination is key, and it requires experts who have the training and expertise to respond, he said.

“It needs to be tracked down, isolated and cleaned up,” Biegalski said.

___

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

NEW YORK — Artificial intelligence company Anthropic has agreed to pay $1.5 billion to settle a class-action lawsuit by book authors who say the company took pirated copies of their works to train its chatbot.

The landmark settlement, if approved by a judge as soon as Monday, could mark a turning point in legal battles between AI companies and the writers, visual artists and other creative professionals who accuse them of copyright infringement.

The company has agreed to pay authors or publishers about $3,000 for each of an estimated 500,000 books covered by the settlement.

“As best as we can tell, it’s the largest copyright recovery ever,” said Justin Nelson, a lawyer for the authors. “It is the first of its kind in the AI era.”

A trio of authors — thriller novelist Andrea Bartz and nonfiction writers Charles Graeber and Kirk Wallace Johnson — sued last year and now represent a broader group of writers and publishers whose books Anthropic downloaded to train its chatbot Claude.

A federal judge dealt the case a mixed ruling in June, finding that training AI chatbots on copyrighted books wasn’t illegal but that Anthropic wrongfully acquired millions of books through pirate websites.

If Anthropic had not settled, experts say losing the case after a scheduled December trial could have cost the San Francisco-based company even more money.

“We were looking at a strong possibility of multiple billions of dollars, enough to potentially cripple or even put Anthropic out of business,” said William Long, a legal analyst for Wolters Kluwer.

U.S. District Judge William Alsup of San Francisco has scheduled a Monday hearing to review the settlement terms.

Anthropic said in a statement Friday that the settlement, if approved, “will resolve the plaintiffs’ remaining legacy claims.”

“We remain committed to developing safe AI systems that help people and organizations extend their capabilities, advance scientific discovery, and solve complex problems,” said Aparna Sridhar, the company’s deputy general counsel.

As part of the settlement, the company has also agreed to destroy the original book files it downloaded.

Books are known to be important sources of data — in essence, billions of words carefully strung together — that are needed to build the AI large language models behind chatbots like Anthropic’s Claude and its chief rival, OpenAI’s ChatGPT.

Alsup’s June ruling found that Anthropic had downloaded more than 7 million digitized books that it “knew had been pirated.” It started with nearly 200,000 from an online library called Books3, assembled by AI researchers outside of OpenAI to match the vast collections on which ChatGPT was trained.

Debut thriller novel “The Lost Night” by Bartz, a lead plaintiff in the case, was among those found in the dataset.

Anthropic later took at least 5 million copies from the pirate website Library Genesis, or LibGen, and at least 2 million copies from the Pirate Library Mirror, Alsup wrote.

The Authors Guild told its thousands of members last month that it expected “damages will be minimally $750 per work and could be much higher” if Anthropic was found at trial to have willfully infringed their copyrights. The settlement’s higher award — approximately $3,000 per work — likely reflects a smaller pool of affected books, after taking out duplicates and those without copyright.

On Friday, Mary Rasenberger, CEO of the Authors Guild, called the settlement “an excellent result for authors, publishers, and rightsholders generally, sending a strong message to the AI industry that there are serious consequences when they pirate authors’ works to train their AI, robbing those least able to afford it.”

The Danish Rights Alliance, which successfully fought to take down one of those shadow libraries, said Friday that the settlement would be of little help to European writers and publishers whose works aren’t registered with the U.S. Copyright Office.

“On the one hand, it’s comforting to see that compiling AI training datasets by downloading millions of books from known illegal file-sharing sites comes at a price,” said Thomas Heldrup, the group’s head of content protection and enforcement.

On the other hand, Heldrup said it fits a tech industry playbook to grow a business first and later pay a relatively small fine, compared to the size of the business, for breaking the rules.

“It is my understanding that these companies see a settlement like the Anthropic one as a price of conducting business in a fiercely competitive space,” Heldrup said.

The privately held Anthropic, founded by ex-OpenAI leaders in 2021, earlier this week put its value at $183 billion after raising another $13 billion in investments.

Anthropic also said it expects to make $5 billion in sales this year, but, like OpenAI and many other AI startups, it has never reported making a profit, relying instead on investors to back the high costs of developing AI technology for the expectation of future payoffs.

The settlement could influence other disputes, including an ongoing lawsuit by authors and newspapers against OpenAI and its business partner Microsoft, and cases against Metaand Midjourney. And just as the Anthropic settlement terms were filed, another group of authors sued Apple on Friday in the same San Francisco federal court.

“This indicates that maybe for other cases, it’s possible for creators and AI companies to reach settlements without having to essentially go for broke in court,” said Long, the legal analyst.

The industry, including Anthropic, had largely praised Alsup’s June ruling because he found that training AI systems on copyrighted works so chatbots can produce their own passages of text qualified as “fair use” under U.S. copyright law because it was “quintessentially transformative.”

Comparing the AI model to “any reader aspiring to be a writer,” Alsup wrote that Anthropic “trained upon works not to race ahead and replicate or supplant them — but to turn a hard corner and create something different.”

But documents disclosed in court showed Anthropic employees’ internal concerns about the legality of their use of pirate sites. The company later shifted its approach and hired Tom Turvey, the former Google executive in charge of Google Books, a searchable library of digitized books that successfully weathered years of copyright battles.

With his help, Anthropic began buying books in bulk, tearing off the bindings and scanning each page before feeding the digitized versions into its AI model, according to court documents. That was legal but didn’t undo the earlier piracy, according to the judge.