PHILADELPHIA -- Aimed at treating rheumatoid arthritis, an investigational antibody drug that stimulates checkpoint activity yielded good results in a phase II study reported here.
After 12 weeks, patients assigned to the drug, called peresolimab, achieved significantly greater improvement in symptoms as assessed through the 28-joint Disease Activity Score (DAS28) and the Clinical Disease Activity Index (CDAI) than did a placebo group, said Paul Emery, MD, of the University of Leeds in England.
In a second phase of the study with no placebo control, which was limited to participants who attained low disease activity in the first 12 weeks, clinical responses were maintained for an additional 12 weeks, Emery told attendees at the American College of Rheumatology's (ACR) annual meeting at a late-breaking abstract session.
Checkpoint-modulating drugs have taken the oncology world by storm in latest years. They seek to counteract tumors' ability to shut down immune attack through the programmed death-1 (PD-1) receptor on immune cells. Those drugs, epitomized by pembrolizumab (Keytruda) and nivolumab (Opdivo), inhibit this pathway.
Peresolimab has the opposite aim: it stimulates the PD-1 receptor as a means of preventing pathogenic immune cells from replicating. This, Emery explained, should rein in the overactivity and "restore normal homeostasis."
His multicenter study appears to be the first to test the hypothesis in rheumatoid arthritis patients.
A total of 98 patients were enrolled, randomized in a 1:2:1 ratio to 300 mg or 700 mg of peresolimab or placebo, each given by infusion every 4 weeks. Participants were typical for such trials: mostly women, mean age of about 50, with disease duration averaging 10 years and substantial current disease activity despite treatment. About 60% were using corticosteroids and nearly half had previously taken a biologic or other targeted agent for rheumatoid arthritis. Mean disease severity scores at baseline were about 5.9 on the DAS28 and 40 with CDAI.
During the initial 12-week phase, similar improvements in all three arms were seen for DAS28 total score and the CDAI up to week 8. At that point, the placebo group had no further improvement while scores on both measures continued to decline (indicating less disease activity) in the two peresolimab groups. Most of the DAS28's individual components showed a similar pattern, except for patients' global assessments, for which no difference was apparent among the three arms.
In general, efficacy was similar for the two peresolimab doses, although trends favored the higher dose on many measures. During the second phase, in which 42 patients in the peresolimab groups who had achieved CDAI scores ≤10 in the first phase continued with dosing for another 12 weeks, CDAI scores remained low with no difference between the dosage groups.
Safety findings were encouraging, Emery said, with no major differences between the active drug and placebo. Infections were numerically greater with peresolimab. Some 8% of the high-dose peresolimab group experienced nausea, which did not occur in the other groups, but there were no discontinuations because of nausea and the effect appeared to be confined to the first few doses.
Following Emery's talk, an audience member asked whether the approach could increase cancer risk, helping early malignancies escape "immune surveillance" and grow more rapidly. Emery replied that this will be evaluated in larger studies, but "there are reasons to believe" that it will not occur; the hypothesized mechanism of action does not suppress normal immune function but rather targets only the overactivity in rheumatoid arthritis, he explained.
A second phase II study in rheumatoid arthritis with planned enrollment of 420 patients recently got underway. Sponsor Eli Lilly had conducted an early trial in psoriasis patients but it was quietly terminated and the company appears to have no further plans for peresolimab in that condition.
Disclosures
The study was sponsored by Eli Lilly. Several authors were Lilly employees. Emery reported relationships with the firm and numerous others.
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A driver was arrested on suspicion of driving under the influence of an illegal drug at a DUI checkpoint in Chula Vista, police said Saturday.
The checkpoint in the 300 block of L Street was conducted from 6 p.m. to midnight Friday.
Of the 1,221 vehicles traveling through the checkpoint, 403 vehicles were screened, said Sgt. Anthony Molina of the Chula Vista Police Department.
Three drivers were given field sobriety tests, the sergeant said. Three vehicles were impounded. Police issued 13 citations to drivers who allegedly were unlicensed or had suspended licenses.
The next checkpoint was scheduled for December.
Checkpoint funding was provided by the California Office of Traffic Safety.
— City News Service
Construction is underway on a new security checkpoint at Denver International Airport. This is the second new checkpoint at the airport as part of the Great Hall Project.
This security checkpoint is on the northeast side of the Jeppesen Terminal. The area on the east side that overlooks north security will be entirely closed and there will be one pathway from bridge security to the north end.
DIA stresses that all security areas will stay open during construction but ask all travelers to check TSA wait times. The new security checkpoint should be completed by 2024.
(CNN) — A gun found inside a raw chicken at an airport security checkpoint has the TSA calling "personal fowl."
The passenger was headed to Port-au-Prince, Haiti, according to Sari Koshetz, a TSA spokesperson for the Gulf region.
Nestor Iglesias, a spokesperson for Homeland Security Investigations, the investigative arm of the US Department of Homeland Security, said he could not offer additional details because it is an "ongoing criminal case which has been accepted for prosecution."
Records have been set at 12 Florida airports, with airports in Orlando (129 guns), Fort Lauderdale (120 guns) and Tampa (102 guns) leading the way.
Nearly all of the guns discovered at checkpoints were loaded, the TSA said, and most had ammunition chambered.
"An accidental discharge could result in tragedy," the TSA's Koshetz said in a statement. "Every passenger bares the responsibility of knowing exactly where their gun is before entering the security checkpoint."
For many passengers, bringing guns to airports resulted in arrests and notices to appear in court.
Civil penalties from the TSA can reach $13,910 even if the passenger is not arrested, the TSA's news release said.
Top image: A gun was found concealed in a chicken at a TSA checkpoint in Florida in late September. (Transportation Security Administration)
Denver International Airport (DEN) has officially begun construction of the second new security checkpoint on Level 6 on the northeast side of the Jeppesen Terminal as part of the Great Hall Completion, the final phase of the airport’s Great Hall Project.
“Earlier this year, we received approval from Denver City Council to move forward on the $1.3 billion Great Hall Completion which will fulfill our original vision for the project by building the second new security checkpoint on Level 6 and constructing and modernizing the remaining ticket lobbies amongst other improvements,” said DEN CEO Phil Washington. “This is a significant milestone as we look to bring an enhanced and more efficient security experience to our passengers.”
All security checkpoints will remain operational during construction and there will always be a corridor open to access the north end of the terminal as well as the Bridge Security. Passengers are strongly encouraged to check live TSA wait times on FlyDenver.com to help them choose the most efficient checkpoint.
The area is separate from the main TSA line. It was used it for the first time Friday morning.
ATLANTA — Officials at Hartsfield-Jackson Atlanta International Airport said they are expecting one million more passengers to come through the airport this Thanksgiving than last year.
A new mini checkpoint area is expected to relieve wait times. The area is separate from the main TSA line. It was used for the first time Friday morning.
“We’re opening up a new auxiliary security checkpoint line downstairs in our lower north level," said Andrew Gobeil, communications director for the airport. "We opened it up for the first time today and it worked fantastic.”
He said the goal is to ease some of the pressure travelers feel during the holidays because of longer wait times.
“We want to make sure that we are on average about 20-25 minutes. Throughout today, we were a little bit below which is good," he said.
Gobeil said the mini checkpoint played a role in that. He also said the more than 60,000 airport employees who normally go through the regular check-in line, will now also go through the mini checkpoint too.
“We will have customer support representatives here to direct people. We’ll have signage out here to direct people,” Gobeil said.
However, that doesn’t mean tossing out the best practice officials recommend, such as arriving two and a half hours early.
Some passengers who had their own tips to mitigate extra time talked to 11Alive Friday. Wesley Watkins wanted to avoid paying an extra bag fee, so he tried something new.
“So, I actually just did this last night – the Army roll. You just roll your clothes up and it all fits in there tighter. It does work, I was shocked," Watkins said.
Briana Lott Thompson said she likes to make it easier to get to her gate.
"Check in on your phone. Prepare for TSA ahead of time and be sure to wear comfy, easy-to-take-off shoes," she said.
The same is true for Rob Ostrowski.
“Leave your host city early in case you need more time and then you can enjoy the trip and can have a cup of coffee," Ostrowski said
Airport officials said they will evaluate how things work with the mini checkpoint over the holiday week to see if they need to make changes.
© Getty Images Stock image. Abandoned cats. A Ukrainian soldier's cat checkpoint has melted hearts online.
A Ukrainian soldier has melted hearts online after a video of him building a "cat checkpoint" in the war-torn country went viral on social media.
The clip, shared on TikTok by the soldier under the username alexandrliashuk, shows him measuring each of the cats before carefully crafting an entry to his hut for them. Made mostly out of wood, bamboo, and plastic, he painted a sign above the door that read: "Cat checkpoint."
Many Ukrainians who are leaving the country are taking pets with them, and most neighboring countries including Hungary, Poland, and Romania are allowing the creatures in with minor paperwork, the People for the Ethical Treatment of Animals (PETA) has said.
More than 7.8 million Ukrainians are currently displaced in Europe, and about 4.7 million of them have registered for temporary protection or similar national protection schemes, according to the United Nations High Commissioner for Refugees (UNHCR).
Since the beginning of the Russian invasion of Ukraine in February, the Office of the United Nations High Commissioner for Human Rights (OHCHR) has Verified a total of 6,490 civilian deaths as of November 6, 2022, with 403 of the victims being children.
Furthermore, 9,972 people were reported to have been injured, although OHCHR said that the true number could be "considerably higher."
The TikTok post, which was first shared on the platform on Thursday, has attracted animal lovers from all over the world, receiving more than 7 million views and 929,000 likes so far.
One user, _notamber, commented: "At first I thought [he was] creating a growth chart for the kitties on the door frame like you do with little kids. This is better and so cute!"
And andeineko said: "The measuring was hilariousss." And happyinlife75 wrote: "The purring while measuring!!" Victoria added: "The way I laughed when he measured their tummies and faces."
Another user, The warmonger, wrote: "Deployment animals bring that comfort in for real. I knew a soldier that brought his deployment cat home. Then got out with it and took it back states." And Cris Kamado said: "This is the most adorable thing ever."
Rhiannon pointed out: "I'm losing it over the one cat that is just completely gone from the world while it's being measured." And _rosewater_ said: "This is what math was made for." KB Toy added: "I would've been content just watching you measure different parts of cats, honestly."
Newsweek reached out to Alexandrliashuk for comment. We could not verify the details of the case.
Do you have funny and adorable videos or pictures of your pet you want to share? Send them to life@newsweek.com with some details about your best friend and they could appear in our Pet of the Week lineup.
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Police have set up a checkpoint in front of BNP Chairperson Khaleda Zia's Gulshan residence in the city tonight.
Syrul Kabir Khan, a staff of the chairperson's media wing, confirmed this to The Daily Star.
Abdul Ahad, deputy commissioner (Gulshan division) of Dhaka Metropolitan Police, said as part of a drive, the number of police checkpoint was increased in Gulshan area.
"Police started setting up checkpoints in different areas of Gulshan tonight. It's part of a special drive to arrest drug peddlers, militants and criminal," the police official told this newspaper.
The Police Headquarters earlier directed the field-level officials to carry out a 15-day special drive across the country from December 1 to ward off any untoward incident ahead of the Victory Day.
Chiefs of all police units and superintendents of police in all districts have been asked to conduct the drive between December 1 and 15, according to an order sent by the operations wing of the PHQ on November 29.
