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David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>165681</fileName> <TBEID>0C04CEBA.SIG</TBEID> <TBUniqueIdentifier>MD_0C04CEBA</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>FastOA Initiative feature story</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20231027T103904</QCDate> <firstPublished>20231027T110133</firstPublished> <LastPublished>20231027T110133</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20231027T110133</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Jennifer Lubell</byline> <bylineText>JENNIFER LUBELL</bylineText> <bylineFull>JENNIFER LUBELL</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>Feature</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. 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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord</metaDescription> <articlePDF/> <teaserImage>298775</teaserImage> <teaser>A new strategy to test investigational treatments for patients with osteoarthritis (OA) is about to begin in patients who are at risk for accelerated development of OA following ACL reconstructive surgery, potentially speeding up the discovery of effective treatments that could be applied to the broader population of patients with OA.</teaser> <title>New initiative aims to test investigational OA treatments in high-risk patients after knee injury</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">27980</term> <term>39313</term> </sections> <topics> <term canonical="true">265</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012360.jpg</altRep> <description role="drol:caption">Dr. David Felson</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012361.jpg</altRep> <description role="drol:caption">Dr. Jason Kim</description> <description role="drol:credit">Ron Hester</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>New initiative aims to test investigational OA treatments in high-risk patients after knee injury</title> <deck/> </itemMeta> <itemContent> <p>David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.</p> <p>[[{"fid":"298775","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"David Felson, MD, MPH, professor of medicine and epidemiology at Boston University","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. David Felson"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said. <br/><br/>Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.<br/><br/>Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain. <br/><br/>There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury. <br/><br/></p> <h2>Previous clinical trials have failed</h2> <p>Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued. </p> <p>However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.<br/><br/>One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta. <br/><br/>[[{"fid":"298776","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation","field_file_image_credit[und][0][value]":"Ron Hester","field_file_image_caption[und][0][value]":"Dr. Jason Kim"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said. <br/><br/>Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said. <br/><br/></p> <h2>Finding patients with ACL reconstruction with ‘bad outcomes’</h2> <p>Dr. Kim and Dr. Felson have joined other researchers to test a <span class="Hyperlink"><a href="https://ard.bmj.com/content/early/2023/10/11/ard-2023-224675">new approach</a></span>, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins. </p> <p>When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer. <br/><br/>“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained. <br/><br/>The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.<br/><br/>A <span class="Hyperlink">longitudinal study known as the MOON trial</span> that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.<br/><br/>Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain. <br/><br/>“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said. <br/><br/></p> <h2>Clinical trial to test FastOA criteria </h2> <p>The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.</p> <p>FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said. <br/><br/>The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added. <br/><br/>The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .<br/><br/>Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will <span class="Hyperlink"><a href="https://www.prnewswire.com/news-releases/arthritis-foundation-announces-first-ever-foundation-directed-post-traumatic-osteoarthritis-clinical-trial-301954223.html">test the use of metformin</a></span>, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction. <br/><br/>Two groups will participate in the <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT06096259">PIKASO trial</a></span>, an initiative of the Arthritis Foundation’s <span class="Hyperlink"><a href="https://www.arthritis.org/science/oa-clinical-trial-network">Osteoarthritis Clinical Trials Network (OA-CTN)</a></span>. <br/><br/>“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.<br/><br/>People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement. <br/><br/>“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said. <br/><br/>Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said. <br/><br/>Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.<br/><br/>Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively. <br/><br/>“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation. <br/><br/></p> <h2>‘We’re taking a leap’</h2> <p>PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.</p> <p>Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said. <br/><br/>Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added. <br/><br/>Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.<br/><br/>“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.<br/><br/>Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.<br/><br/>The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.<br/><br/>PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken. <br/><br/>“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure. <br/><br/>“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.<br/><br/>Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.<br/><br/>While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said. <br/><br/>“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said. <br/><br/>The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024. <br/><br/>Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.<span class="end"><br/><br/></span> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
