Federal Practitioner

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

A version of this article first appeared on Medscape.com.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

A version of this article first appeared on Medscape.com.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

A version of this article first appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

A version of this article first appeared on WebMD.com.

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

A version of this article first appeared on WebMD.com.

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

A version of this article first appeared on WebMD.com.

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

A version of this article first appeared on Medscape.com.

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

A version of this article first appeared on Medscape.com.

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

A version of this article first appeared on Medscape.com.

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.