Osteoarthritis

The Food and Drug Administration announced on Dec. 4 that it recommends the voluntary recall of Limbrel, a medical food product in capsule form that is currently marketed to “manage the metabolic processes associated with osteoarthritis.”

The FDA’s ongoing investigation at this point considers the product to be an unapproved new drug rather than a medical food product. However, the agency does not have mandatory recall authority. It has recommended the recall to the product’s manufacturer, Primus Pharmaceuticals, on the basis of the risk of liver injury and hypersensitivity pneumonitis associated with continued use of the product.

The agency had received 194 adverse event reports as of Nov. 21, of which it found a likely association of the events with Limbrel in at least 30 cases, and continues to evaluate reports, which consumers can submit through MedWatch. The FDA is currently testing samples of the product and has advised consumers to cease taking it, though the manufacturer has declined thus far to recall it.

The safety alert advises that “health care providers who are aware that their patients are taking Limbrel should advise them to immediately stop taking the product.”

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The Food and Drug Administration announced on Dec. 4 that it recommends the voluntary recall of Limbrel, a medical food product in capsule form that is currently marketed to “manage the metabolic processes associated with osteoarthritis.”

The FDA’s ongoing investigation at this point considers the product to be an unapproved new drug rather than a medical food product. However, the agency does not have mandatory recall authority. It has recommended the recall to the product’s manufacturer, Primus Pharmaceuticals, on the basis of the risk of liver injury and hypersensitivity pneumonitis associated with continued use of the product.

The agency had received 194 adverse event reports as of Nov. 21, of which it found a likely association of the events with Limbrel in at least 30 cases, and continues to evaluate reports, which consumers can submit through MedWatch. The FDA is currently testing samples of the product and has advised consumers to cease taking it, though the manufacturer has declined thus far to recall it.

The safety alert advises that “health care providers who are aware that their patients are taking Limbrel should advise them to immediately stop taking the product.”

[email protected]

The Food and Drug Administration announced on Dec. 4 that it recommends the voluntary recall of Limbrel, a medical food product in capsule form that is currently marketed to “manage the metabolic processes associated with osteoarthritis.”

The FDA’s ongoing investigation at this point considers the product to be an unapproved new drug rather than a medical food product. However, the agency does not have mandatory recall authority. It has recommended the recall to the product’s manufacturer, Primus Pharmaceuticals, on the basis of the risk of liver injury and hypersensitivity pneumonitis associated with continued use of the product.

The agency had received 194 adverse event reports as of Nov. 21, of which it found a likely association of the events with Limbrel in at least 30 cases, and continues to evaluate reports, which consumers can submit through MedWatch. The FDA is currently testing samples of the product and has advised consumers to cease taking it, though the manufacturer has declined thus far to recall it.

The safety alert advises that “health care providers who are aware that their patients are taking Limbrel should advise them to immediately stop taking the product.”

[email protected]

The prevalence of arthritis in the United States is much higher than current estimates indicate, especially among adults under 65 years of age, a study showed.

The higher prevalence can be largely attributed to “the previous underestimate of arthritis in adults between 18-64 years of age,” according to S. Reza Jafarzadeh, PhD, and David T. Felson , MD, both of Boston University. Using a new surveillance model, they estimated that 91.2 million adults in the United States (36.8%) had arthritis in 2015, compared with a previously reported national estimate of 54.4 million adults (22.7%). Of these, 61.1 million were between 18 and 64 years of age (Arthritis Rheumatol. 2017 Nov 27. doi: 10.1002/art.40355).

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The prevalence of arthritis in the United States is much higher than current estimates indicate, especially among adults under 65 years of age, a study showed.

The higher prevalence can be largely attributed to “the previous underestimate of arthritis in adults between 18-64 years of age,” according to S. Reza Jafarzadeh, PhD, and David T. Felson , MD, both of Boston University. Using a new surveillance model, they estimated that 91.2 million adults in the United States (36.8%) had arthritis in 2015, compared with a previously reported national estimate of 54.4 million adults (22.7%). Of these, 61.1 million were between 18 and 64 years of age (Arthritis Rheumatol. 2017 Nov 27. doi: 10.1002/art.40355).

[email protected]

The prevalence of arthritis in the United States is much higher than current estimates indicate, especially among adults under 65 years of age, a study showed.

The higher prevalence can be largely attributed to “the previous underestimate of arthritis in adults between 18-64 years of age,” according to S. Reza Jafarzadeh, PhD, and David T. Felson , MD, both of Boston University. Using a new surveillance model, they estimated that 91.2 million adults in the United States (36.8%) had arthritis in 2015, compared with a previously reported national estimate of 54.4 million adults (22.7%). Of these, 61.1 million were between 18 and 64 years of age (Arthritis Rheumatol. 2017 Nov 27. doi: 10.1002/art.40355).

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SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.

“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”

Doug Brunk/Frontline Medical News

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SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.

“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”

Doug Brunk/Frontline Medical News

[email protected]

SAN DIEGO – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.

“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD, said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”

Doug Brunk/Frontline Medical News

[email protected]

Flexion Therapeutics announced Oct. 6 the approval of Zilretta (triamcinolone acetonide extended-release injectable suspension) as the first and only extended-release, intra-articular injection for osteoarthritis knee pain.

Zilretta uses a proprietary microsphere-based formulation of triamcinolone acetonide to provide pain relief over 12 weeks by prolonging the release of triamcinolone acetonide inside the synovial fluid. The approval is based on data from a phase 3 clinical trial. The randomized, double-blind study enrolled 484 patients at 37 centers worldwide. The label also includes the results from a double-blind, randomized, parallel-group trial, which examined blood glucose concentrations in patients with type 2 diabetes to show how Zilretta can avoid blood glucose spikes observed with corticosteroid use.

[email protected]

Flexion Therapeutics announced Oct. 6 the approval of Zilretta (triamcinolone acetonide extended-release injectable suspension) as the first and only extended-release, intra-articular injection for osteoarthritis knee pain.

Zilretta uses a proprietary microsphere-based formulation of triamcinolone acetonide to provide pain relief over 12 weeks by prolonging the release of triamcinolone acetonide inside the synovial fluid. The approval is based on data from a phase 3 clinical trial. The randomized, double-blind study enrolled 484 patients at 37 centers worldwide. The label also includes the results from a double-blind, randomized, parallel-group trial, which examined blood glucose concentrations in patients with type 2 diabetes to show how Zilretta can avoid blood glucose spikes observed with corticosteroid use.

[email protected]

Flexion Therapeutics announced Oct. 6 the approval of Zilretta (triamcinolone acetonide extended-release injectable suspension) as the first and only extended-release, intra-articular injection for osteoarthritis knee pain.

Zilretta uses a proprietary microsphere-based formulation of triamcinolone acetonide to provide pain relief over 12 weeks by prolonging the release of triamcinolone acetonide inside the synovial fluid. The approval is based on data from a phase 3 clinical trial. The randomized, double-blind study enrolled 484 patients at 37 centers worldwide. The label also includes the results from a double-blind, randomized, parallel-group trial, which examined blood glucose concentrations in patients with type 2 diabetes to show how Zilretta can avoid blood glucose spikes observed with corticosteroid use.

[email protected]

BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”

Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.

“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.

“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.

[email protected]

BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”

Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.

“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.

“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.

[email protected]

BARCELONA – For Clyde Yancy, MD, presentation of the bombshell CANTOS trial results at the annual congress of the European Congress of Cardiology made for “a really good day.”

Those results showed that inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer. But further, they introduced a new way of identifying and treating patients for secondary prevention.

“Here is an alternative way to get to cardiovascular events; here is bringing inflammation right to the front page of what we do as cardiologists to prevent events; here is a brand-new agent that is a monoclonal antibody against interleukin that may be modifying this risk, and … a remarkable advantage that really needs to be replicated,” said Dr. Yancy, chief of medicine-cardiology at Northwestern University in Chicago, in a video interview.

“This is a really good day” because we’ve got new things to think about, new ways to approach our patients, and [we may soon be] entering the realm where we’ll want personalized therapy based on the unique phenotype a patient represents, and think about the pathways to disease through these brand new schemes” that are helping us understand the burden of disease, he declared.

[email protected]

BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.

“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.

He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).

“These results will have impact on your daily practice when you go home,” the cardiologist promised.

PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).

The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.

The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.

The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.

Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.

“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”

Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”

Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.

“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).

“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.

That report triggered a fevered reaction.

“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.

Dr. Ruschitzka discussed his findings in a video interview.

PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.

[email protected]

BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.

“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.

He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).

“These results will have impact on your daily practice when you go home,” the cardiologist promised.

PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).

The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.

The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.

The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.

Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.

“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”

Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”

Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.

“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).

“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.

That report triggered a fevered reaction.

“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.

Dr. Ruschitzka discussed his findings in a video interview.

PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.

[email protected]

BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.

“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.

He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).

“These results will have impact on your daily practice when you go home,” the cardiologist promised.

PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).

The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.

The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.

The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.

Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.

“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”

Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”

Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.

“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.

Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).

“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.

That report triggered a fevered reaction.

“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.

Dr. Ruschitzka discussed his findings in a video interview.

PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.

[email protected]

MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.

In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.

copyright Nandyphotos/Thinkstock

Synthetic trans-capsaicin CNTX-4975

“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.

CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.

The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m², and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.

The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.

The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).

“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.

The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.

A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).

“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.

Wnt inhibitor SM04690

Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.

Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.

SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.

Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.

In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.

Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.

A total of 455 subjects, mean age 60 years, were randomized into the trial.

Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.

An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.

The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).

However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.

Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.

“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.

The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.

MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.

In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.

copyright Nandyphotos/Thinkstock

Synthetic trans-capsaicin CNTX-4975

“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.

CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.

The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m², and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.

The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.

The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).

“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.

The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.

A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).

“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.

Wnt inhibitor SM04690

Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.

Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.

SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.

Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.

In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.

Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.

A total of 455 subjects, mean age 60 years, were randomized into the trial.

Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.

An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.

The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).

However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.

Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.

“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.

The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.

MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.

In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.

copyright Nandyphotos/Thinkstock

Synthetic trans-capsaicin CNTX-4975

“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.

CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.

The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m², and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.

The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.

The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).

“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.

The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.

A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).

“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.

Wnt inhibitor SM04690

Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.

Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.

SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.

Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.

In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.

Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.

A total of 455 subjects, mean age 60 years, were randomized into the trial.

Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.

An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.

The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).

However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.

Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.

“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.

The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.

MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.

The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.

Sara Freeman/Frontline Medical News

Disappointing results with cytokine targeting

Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.

While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.

Sara Freeman/Frontline Medical News

[email protected]

On Twitter @rheumnews1

MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.

The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.

Sara Freeman/Frontline Medical News

Disappointing results with cytokine targeting

Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.

While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.

Sara Freeman/Frontline Medical News

[email protected]

On Twitter @rheumnews1

MADRID – Treatment with the dual interleukin (IL) 1 blocker ABT-981 did not improve pain scores or erosive joint damage in patients with hand osteoarthritis (OA) in a phase 2a trial reported at the European Congress of Rheumatology.

The disappointing findings suggest that IL-1 may not be an effective target in erosive hand OA, said Margreet Kloppenburg, MD, of Leiden (the Netherlands) University Medical Center, even though the investigators obtained adequate pharmacodynamic results that suggested it was effectively blocking both IL-1 alpha and IL-1 beta.

Sara Freeman/Frontline Medical News

Disappointing results with cytokine targeting

Hand OA affects around 11% of the OA population and erosive hand OA is a very painful phenotype that affects multiple joints, Xavier Chevalier, MD, of Henri-Mondor Hospital, Paris XII University (France), said during a separate session at the congress.

While there is a rationale for using anti-inflammatory drugs for erosive hand OA, so far there just have not been many, if any, real successes. “The effect sizes are small,” Dr. Chevalier said. “There are not a lot of drugs when compared to hip and knee OA,” he observed.

Sara Freeman/Frontline Medical News

[email protected]

On Twitter @rheumnews1

LAS VEGAS – Childhood overweight was associated with increased risk of patellar cartilage defects in young adulthood independent of adult weight status in what’s believed to be the first long-term prospective study to address the issue using informative MRI imaging.

“Our data indicate the importance of intervening in childhood obesity for adult joint health,” Benny E. Antony, MD, reported at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

He presented the 25-year prospective follow-up from the population-based Childhood Determinants of Adult Knee Cartilage Study, a substudy of the Australian Schools Health and Fitness Survey of 1985. The analysis included 322 nationally representative participants who were 7-15 years old at enrollment and 31-41 years old at follow-up, when they underwent screening MRI knee scans in which cartilage defects in the tibial, femoral, and patellar zones were rated by a modified Outerbridge scoring system.

• Women had a higher prevalence of cartilage defects: 43% in the whole knee and 30% at the patella, compared with rates of 34% and 20%, respectively, in men.

• The prevalence of patellar cartilage defects in young adulthood was 24.2% in those who had a normal weight both as children and young adults compared with 40% in participants who were overweight at both time points, for an adjusted 1.77-fold increased risk in subjects who were overweight across the decades, .

• Excess childhood weight per kilogram, fat mass per kilogram, and body mass per unit were each associated with 5%-12% increased risks of patellar cartilage defects 25 years later, independent of adult body weight status, in an analysis adjusted for childhood age, sex, height, duration of follow-up, and history of pediatric or adult knee injury.

• A dose-response relationship was evident between the degree of childhood overweight and the severity of cartilage defects as young adults on a 0-4 rating scale.

Dr. Antony reported having no financial conflicts of interest regarding the study, which was supported by the National Health and Medical Research Council of Australia.

[email protected]

LAS VEGAS – Childhood overweight was associated with increased risk of patellar cartilage defects in young adulthood independent of adult weight status in what’s believed to be the first long-term prospective study to address the issue using informative MRI imaging.

“Our data indicate the importance of intervening in childhood obesity for adult joint health,” Benny E. Antony, MD, reported at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

He presented the 25-year prospective follow-up from the population-based Childhood Determinants of Adult Knee Cartilage Study, a substudy of the Australian Schools Health and Fitness Survey of 1985. The analysis included 322 nationally representative participants who were 7-15 years old at enrollment and 31-41 years old at follow-up, when they underwent screening MRI knee scans in which cartilage defects in the tibial, femoral, and patellar zones were rated by a modified Outerbridge scoring system.

• Women had a higher prevalence of cartilage defects: 43% in the whole knee and 30% at the patella, compared with rates of 34% and 20%, respectively, in men.

• The prevalence of patellar cartilage defects in young adulthood was 24.2% in those who had a normal weight both as children and young adults compared with 40% in participants who were overweight at both time points, for an adjusted 1.77-fold increased risk in subjects who were overweight across the decades, .

• Excess childhood weight per kilogram, fat mass per kilogram, and body mass per unit were each associated with 5%-12% increased risks of patellar cartilage defects 25 years later, independent of adult body weight status, in an analysis adjusted for childhood age, sex, height, duration of follow-up, and history of pediatric or adult knee injury.

• A dose-response relationship was evident between the degree of childhood overweight and the severity of cartilage defects as young adults on a 0-4 rating scale.

Dr. Antony reported having no financial conflicts of interest regarding the study, which was supported by the National Health and Medical Research Council of Australia.

[email protected]

LAS VEGAS – Childhood overweight was associated with increased risk of patellar cartilage defects in young adulthood independent of adult weight status in what’s believed to be the first long-term prospective study to address the issue using informative MRI imaging.

“Our data indicate the importance of intervening in childhood obesity for adult joint health,” Benny E. Antony, MD, reported at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

He presented the 25-year prospective follow-up from the population-based Childhood Determinants of Adult Knee Cartilage Study, a substudy of the Australian Schools Health and Fitness Survey of 1985. The analysis included 322 nationally representative participants who were 7-15 years old at enrollment and 31-41 years old at follow-up, when they underwent screening MRI knee scans in which cartilage defects in the tibial, femoral, and patellar zones were rated by a modified Outerbridge scoring system.

• Women had a higher prevalence of cartilage defects: 43% in the whole knee and 30% at the patella, compared with rates of 34% and 20%, respectively, in men.

• The prevalence of patellar cartilage defects in young adulthood was 24.2% in those who had a normal weight both as children and young adults compared with 40% in participants who were overweight at both time points, for an adjusted 1.77-fold increased risk in subjects who were overweight across the decades, .

• Excess childhood weight per kilogram, fat mass per kilogram, and body mass per unit were each associated with 5%-12% increased risks of patellar cartilage defects 25 years later, independent of adult body weight status, in an analysis adjusted for childhood age, sex, height, duration of follow-up, and history of pediatric or adult knee injury.

• A dose-response relationship was evident between the degree of childhood overweight and the severity of cartilage defects as young adults on a 0-4 rating scale.

Dr. Antony reported having no financial conflicts of interest regarding the study, which was supported by the National Health and Medical Research Council of Australia.

[email protected]

LAS VEGAS – One of the most intriguing clues that suggest the metabolic syndrome or one of its components might cause hand osteoarthritis comes from a recent study of middle-aged HIV-positive patients, David T. Felson, MD, asserted at the World Congress on Osteoarthritis.

“This is an important study. The identification of an unusual cohort, which otherwise wasn’t supposed to get a particular disease, has really helped us to determine the cause of diseases in other circumstances,” said Dr. Felson, a rheumatologist who is professor of medicine and epidemiology and director of the clinical epidemiology research and training unit at Boston University. He cited an example that also happens to have been related to HIV: Kaposi’s sarcoma in gay men “that alerted us initially to the existence of HIV infection,” he commented.

Other evidence to suggest that metabolic factors are causally related to hand OA comes from animal models, as well as from large population-based cohort studies, including the Netherlands Epidemiology of Obesity (NEO) study. NEO involved 6,673 middle-aged Dutch men and women. Metabolic syndrome was associated with increased rates of both hand OA and knee OA in analyses unadjusted for body weight. However, when the Leiden University investigators adjusted for body weight, the association between metabolic syndrome and knee OA went away, whereas the association between metabolic syndrome and hand OA remained strong (Ann Rheum Dis. 2015 Oct;74[10]:1842-7).

This has uniformly been the case in other cohort studies reporting an association between metabolic syndrome and knee OA: upon adjusting for body mass index (BMI), there is no longer a residual relationship between metabolic syndrome and knee OA.

“One of the challenges in studying metabolic syndrome and knee osteoarthritis is that all the components of the metabolic syndrome are strongly correlated with obesity, and obesity is a major risk factor for knee osteoarthritis through its effects on joint loading. So obesity – at least for knee osteoarthritis – is an enormous confounder,” Dr. Felson said.

The findings from NEO and other large cohort studies underscore a key point: “Metabolic syndrome is not a risk factor for knee osteoarthritis, despite a lot of hullabaloo to the contrary. It doesn’t emerge in cohort studies as an important factor,” according to the rheum

Thinkstock/ LarsNeumann

[email protected]
 

LAS VEGAS – One of the most intriguing clues that suggest the metabolic syndrome or one of its components might cause hand osteoarthritis comes from a recent study of middle-aged HIV-positive patients, David T. Felson, MD, asserted at the World Congress on Osteoarthritis.

“This is an important study. The identification of an unusual cohort, which otherwise wasn’t supposed to get a particular disease, has really helped us to determine the cause of diseases in other circumstances,” said Dr. Felson, a rheumatologist who is professor of medicine and epidemiology and director of the clinical epidemiology research and training unit at Boston University. He cited an example that also happens to have been related to HIV: Kaposi’s sarcoma in gay men “that alerted us initially to the existence of HIV infection,” he commented.

Other evidence to suggest that metabolic factors are causally related to hand OA comes from animal models, as well as from large population-based cohort studies, including the Netherlands Epidemiology of Obesity (NEO) study. NEO involved 6,673 middle-aged Dutch men and women. Metabolic syndrome was associated with increased rates of both hand OA and knee OA in analyses unadjusted for body weight. However, when the Leiden University investigators adjusted for body weight, the association between metabolic syndrome and knee OA went away, whereas the association between metabolic syndrome and hand OA remained strong (Ann Rheum Dis. 2015 Oct;74[10]:1842-7).

This has uniformly been the case in other cohort studies reporting an association between metabolic syndrome and knee OA: upon adjusting for body mass index (BMI), there is no longer a residual relationship between metabolic syndrome and knee OA.

“One of the challenges in studying metabolic syndrome and knee osteoarthritis is that all the components of the metabolic syndrome are strongly correlated with obesity, and obesity is a major risk factor for knee osteoarthritis through its effects on joint loading. So obesity – at least for knee osteoarthritis – is an enormous confounder,” Dr. Felson said.

The findings from NEO and other large cohort studies underscore a key point: “Metabolic syndrome is not a risk factor for knee osteoarthritis, despite a lot of hullabaloo to the contrary. It doesn’t emerge in cohort studies as an important factor,” according to the rheum

Thinkstock/ LarsNeumann

[email protected]
 

LAS VEGAS – One of the most intriguing clues that suggest the metabolic syndrome or one of its components might cause hand osteoarthritis comes from a recent study of middle-aged HIV-positive patients, David T. Felson, MD, asserted at the World Congress on Osteoarthritis.

“This is an important study. The identification of an unusual cohort, which otherwise wasn’t supposed to get a particular disease, has really helped us to determine the cause of diseases in other circumstances,” said Dr. Felson, a rheumatologist who is professor of medicine and epidemiology and director of the clinical epidemiology research and training unit at Boston University. He cited an example that also happens to have been related to HIV: Kaposi’s sarcoma in gay men “that alerted us initially to the existence of HIV infection,” he commented.

Other evidence to suggest that metabolic factors are causally related to hand OA comes from animal models, as well as from large population-based cohort studies, including the Netherlands Epidemiology of Obesity (NEO) study. NEO involved 6,673 middle-aged Dutch men and women. Metabolic syndrome was associated with increased rates of both hand OA and knee OA in analyses unadjusted for body weight. However, when the Leiden University investigators adjusted for body weight, the association between metabolic syndrome and knee OA went away, whereas the association between metabolic syndrome and hand OA remained strong (Ann Rheum Dis. 2015 Oct;74[10]:1842-7).

This has uniformly been the case in other cohort studies reporting an association between metabolic syndrome and knee OA: upon adjusting for body mass index (BMI), there is no longer a residual relationship between metabolic syndrome and knee OA.

“One of the challenges in studying metabolic syndrome and knee osteoarthritis is that all the components of the metabolic syndrome are strongly correlated with obesity, and obesity is a major risk factor for knee osteoarthritis through its effects on joint loading. So obesity – at least for knee osteoarthritis – is an enormous confounder,” Dr. Felson said.

The findings from NEO and other large cohort studies underscore a key point: “Metabolic syndrome is not a risk factor for knee osteoarthritis, despite a lot of hullabaloo to the contrary. It doesn’t emerge in cohort studies as an important factor,” according to the rheum

Thinkstock/ LarsNeumann

[email protected]