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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Experts bust common sports medicine myths
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44).
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44).
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44).
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
Depressed OA patients get far-reaching benefits from Internet-delivered CBT
Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.
The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).
The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.
The investigators randomized the participants to the 10-week Internet cognitive behavioral therapy (iCBT) Sadness Program in addition to usual treatment or to a control group that received usual treatment. Participants were followed up at 1 week and 3 months after the intervention. The iCBT Sadness Program consists of six online lessons representing best practice CBT, as well as regular homework assignments and access to supplementary resources. The program has been validated in several clinical efficacy and effectiveness trials.
The iCBT program proved superior to usual treatment on the primary outcomes of depression as measured by the Patient Health Questionnaire (PHQ-9) and psychological distress (measured using Kessler-10). In particular, a large between-group effect size was seen for PHQ-9 scores (Hedge’s g = 1.01; 95% confidence interval [CI], 0.47-1.54) and a medium effect size for the Kessler-10 score (Hedge’s g = 0.75, 95% CI, 0.23-1.28).
At 3-month follow-up, large between-group effect sizes developed between the iCBT group and the usual treatment-only group on the PHQ-9 (Hedge’s g = 0.90, 95% CI, 0.36-1.44) and Kessler-10 (Hedge’s g = 0.94, 95% CI, 0.41-1.48).
In the iCBT group, the intervention produced large effect-size reductions in depression and distress from pre- to posttreatment and from pretreatment to 12-week follow-up, but in the usual treatment-only group, the effect-size reductions were small and not significant.
In terms of clinical significance, the authors noted that 21 (47.7%) of the participants in the iCBT group “reliably improved,” compared with 3 participants (12%) in the usual treatment-only group.
At 3-month follow-up, 33 participants (84.6%) in the iCBT group no longer met the criteria for major depression, compared with 11 (50%) of the control group.
The intervention also improved the secondary outcomes of OA-specific pain, stiffness, and physical functioning on the Western Ontario and McMaster Osteoarthritis Index and Arthritis Self-Efficacy Scale score, but this was seen by the research team only at the 3-month follow-up. They suggested that further studies should evaluate whether the intervention reduced pain-related catastrophic cognitions or sensitivity to pain and improved a patients’ estimation of their own ability and/or adherence to pain management.
“The outcomes of these studies may provide insight into why there were no significant changes in global physical functioning and no between-group differences for arthritis-related self-efficacy, pain, stiffness, and physical function directly following the program, yet differences emerged 3 months later,” the researchers noted.
They suggested that changes in OA-specific variables such as pain or self efficacy likely required time to interact with cognitive change mechanisms that occur through iCBT.
“It is possible that reduced depressive symptoms result in flow-on effects to OA variables over time and perhaps programs that specifically target OA management may show more immediate effects,” they added.
The researchers concluded that a biopsychosocial approach to managing people with OA was consistent with the recent emphasis on a holistic assessment of older patients with OA.
“These findings are significant given iCBT programs can overcome barriers to receiving face-to-face psychological and/or pharmacological treatment in this population, such as cost, lack of accessibility, and pharmacological side-effects and interactions,” the study authors wrote.
“Medical management of OA of the knee could be supplemented with integrated evidence-based depression treatment, including iCBT, to maximize functional status and mental health well-being,” they added.
The study was funded by grants from the Australian National Health and Medical Research Council. The authors declared no relevant conflicts of interest.
Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.
The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).
The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.
The investigators randomized the participants to the 10-week Internet cognitive behavioral therapy (iCBT) Sadness Program in addition to usual treatment or to a control group that received usual treatment. Participants were followed up at 1 week and 3 months after the intervention. The iCBT Sadness Program consists of six online lessons representing best practice CBT, as well as regular homework assignments and access to supplementary resources. The program has been validated in several clinical efficacy and effectiveness trials.
The iCBT program proved superior to usual treatment on the primary outcomes of depression as measured by the Patient Health Questionnaire (PHQ-9) and psychological distress (measured using Kessler-10). In particular, a large between-group effect size was seen for PHQ-9 scores (Hedge’s g = 1.01; 95% confidence interval [CI], 0.47-1.54) and a medium effect size for the Kessler-10 score (Hedge’s g = 0.75, 95% CI, 0.23-1.28).
At 3-month follow-up, large between-group effect sizes developed between the iCBT group and the usual treatment-only group on the PHQ-9 (Hedge’s g = 0.90, 95% CI, 0.36-1.44) and Kessler-10 (Hedge’s g = 0.94, 95% CI, 0.41-1.48).
In the iCBT group, the intervention produced large effect-size reductions in depression and distress from pre- to posttreatment and from pretreatment to 12-week follow-up, but in the usual treatment-only group, the effect-size reductions were small and not significant.
In terms of clinical significance, the authors noted that 21 (47.7%) of the participants in the iCBT group “reliably improved,” compared with 3 participants (12%) in the usual treatment-only group.
At 3-month follow-up, 33 participants (84.6%) in the iCBT group no longer met the criteria for major depression, compared with 11 (50%) of the control group.
The intervention also improved the secondary outcomes of OA-specific pain, stiffness, and physical functioning on the Western Ontario and McMaster Osteoarthritis Index and Arthritis Self-Efficacy Scale score, but this was seen by the research team only at the 3-month follow-up. They suggested that further studies should evaluate whether the intervention reduced pain-related catastrophic cognitions or sensitivity to pain and improved a patients’ estimation of their own ability and/or adherence to pain management.
“The outcomes of these studies may provide insight into why there were no significant changes in global physical functioning and no between-group differences for arthritis-related self-efficacy, pain, stiffness, and physical function directly following the program, yet differences emerged 3 months later,” the researchers noted.
They suggested that changes in OA-specific variables such as pain or self efficacy likely required time to interact with cognitive change mechanisms that occur through iCBT.
“It is possible that reduced depressive symptoms result in flow-on effects to OA variables over time and perhaps programs that specifically target OA management may show more immediate effects,” they added.
The researchers concluded that a biopsychosocial approach to managing people with OA was consistent with the recent emphasis on a holistic assessment of older patients with OA.
“These findings are significant given iCBT programs can overcome barriers to receiving face-to-face psychological and/or pharmacological treatment in this population, such as cost, lack of accessibility, and pharmacological side-effects and interactions,” the study authors wrote.
“Medical management of OA of the knee could be supplemented with integrated evidence-based depression treatment, including iCBT, to maximize functional status and mental health well-being,” they added.
The study was funded by grants from the Australian National Health and Medical Research Council. The authors declared no relevant conflicts of interest.
Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.
The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).
The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.
The investigators randomized the participants to the 10-week Internet cognitive behavioral therapy (iCBT) Sadness Program in addition to usual treatment or to a control group that received usual treatment. Participants were followed up at 1 week and 3 months after the intervention. The iCBT Sadness Program consists of six online lessons representing best practice CBT, as well as regular homework assignments and access to supplementary resources. The program has been validated in several clinical efficacy and effectiveness trials.
The iCBT program proved superior to usual treatment on the primary outcomes of depression as measured by the Patient Health Questionnaire (PHQ-9) and psychological distress (measured using Kessler-10). In particular, a large between-group effect size was seen for PHQ-9 scores (Hedge’s g = 1.01; 95% confidence interval [CI], 0.47-1.54) and a medium effect size for the Kessler-10 score (Hedge’s g = 0.75, 95% CI, 0.23-1.28).
At 3-month follow-up, large between-group effect sizes developed between the iCBT group and the usual treatment-only group on the PHQ-9 (Hedge’s g = 0.90, 95% CI, 0.36-1.44) and Kessler-10 (Hedge’s g = 0.94, 95% CI, 0.41-1.48).
In the iCBT group, the intervention produced large effect-size reductions in depression and distress from pre- to posttreatment and from pretreatment to 12-week follow-up, but in the usual treatment-only group, the effect-size reductions were small and not significant.
In terms of clinical significance, the authors noted that 21 (47.7%) of the participants in the iCBT group “reliably improved,” compared with 3 participants (12%) in the usual treatment-only group.
At 3-month follow-up, 33 participants (84.6%) in the iCBT group no longer met the criteria for major depression, compared with 11 (50%) of the control group.
The intervention also improved the secondary outcomes of OA-specific pain, stiffness, and physical functioning on the Western Ontario and McMaster Osteoarthritis Index and Arthritis Self-Efficacy Scale score, but this was seen by the research team only at the 3-month follow-up. They suggested that further studies should evaluate whether the intervention reduced pain-related catastrophic cognitions or sensitivity to pain and improved a patients’ estimation of their own ability and/or adherence to pain management.
“The outcomes of these studies may provide insight into why there were no significant changes in global physical functioning and no between-group differences for arthritis-related self-efficacy, pain, stiffness, and physical function directly following the program, yet differences emerged 3 months later,” the researchers noted.
They suggested that changes in OA-specific variables such as pain or self efficacy likely required time to interact with cognitive change mechanisms that occur through iCBT.
“It is possible that reduced depressive symptoms result in flow-on effects to OA variables over time and perhaps programs that specifically target OA management may show more immediate effects,” they added.
The researchers concluded that a biopsychosocial approach to managing people with OA was consistent with the recent emphasis on a holistic assessment of older patients with OA.
“These findings are significant given iCBT programs can overcome barriers to receiving face-to-face psychological and/or pharmacological treatment in this population, such as cost, lack of accessibility, and pharmacological side-effects and interactions,” the study authors wrote.
“Medical management of OA of the knee could be supplemented with integrated evidence-based depression treatment, including iCBT, to maximize functional status and mental health well-being,” they added.
The study was funded by grants from the Australian National Health and Medical Research Council. The authors declared no relevant conflicts of interest.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: At 3-month follow-up, 33 participants (84.6%) in the iCBT group no longer met the criteria for major depression, compared with 11 (50%) of the control group.
Data Source: A randomized, controlled trial of 69 adults aged 50 years or older with major depressive disorder and symptomatic osteoarthritis of the knee.
Disclosures: The study was funded by grants from the Australian National Health and Medical Research Council. The authors declared no relevant conflicts of interest.
Knee injuries in youth sports bring double whammy
LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.
“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.
She presented highlights from the Alberta Youth Prevention in Early OA study, an ongoing prospective longitudinal cohort study of the long-term consequences of sports-related knee injury. The study includes 100 individuals who experienced a sports-related intra-articular knee injury 3-10 years earlier, prior to age 18 years, and 100 controls matched for age, sex, and participation in the same sport but without a knee injury. Their median age at follow-up was 22 years. Their knee injury occurred at a median age of 16 years; 55% of subjects were female.
It’s well established from other studies that roughly 50% of youth who have a significant knee joint injury for which they seek medical attention go on to develop knee osteoarthritis within 10-15 years. The Alberta study focuses on the years between injury and OA onset in an effort to identify modifiable risk factors and develop interventions to delay or halt progression to the disease. There is a paucity of research regarding this crucial time period, Dr. Whittaker explained at the congress sponsored by the Osteoarthritis Research Society International.
“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.
At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.
“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.
“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.
Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.
“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.
She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.
“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.
The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.
LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.
“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.
She presented highlights from the Alberta Youth Prevention in Early OA study, an ongoing prospective longitudinal cohort study of the long-term consequences of sports-related knee injury. The study includes 100 individuals who experienced a sports-related intra-articular knee injury 3-10 years earlier, prior to age 18 years, and 100 controls matched for age, sex, and participation in the same sport but without a knee injury. Their median age at follow-up was 22 years. Their knee injury occurred at a median age of 16 years; 55% of subjects were female.
It’s well established from other studies that roughly 50% of youth who have a significant knee joint injury for which they seek medical attention go on to develop knee osteoarthritis within 10-15 years. The Alberta study focuses on the years between injury and OA onset in an effort to identify modifiable risk factors and develop interventions to delay or halt progression to the disease. There is a paucity of research regarding this crucial time period, Dr. Whittaker explained at the congress sponsored by the Osteoarthritis Research Society International.
“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.
At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.
“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.
“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.
Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.
“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.
She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.
“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.
The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.
LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.
“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.
She presented highlights from the Alberta Youth Prevention in Early OA study, an ongoing prospective longitudinal cohort study of the long-term consequences of sports-related knee injury. The study includes 100 individuals who experienced a sports-related intra-articular knee injury 3-10 years earlier, prior to age 18 years, and 100 controls matched for age, sex, and participation in the same sport but without a knee injury. Their median age at follow-up was 22 years. Their knee injury occurred at a median age of 16 years; 55% of subjects were female.
It’s well established from other studies that roughly 50% of youth who have a significant knee joint injury for which they seek medical attention go on to develop knee osteoarthritis within 10-15 years. The Alberta study focuses on the years between injury and OA onset in an effort to identify modifiable risk factors and develop interventions to delay or halt progression to the disease. There is a paucity of research regarding this crucial time period, Dr. Whittaker explained at the congress sponsored by the Osteoarthritis Research Society International.
“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.
At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.
“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.
“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.
Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.
“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.
She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.
“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.
The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.
Key clinical point:
Major finding: Just 3-10 years after sustaining a knee injury while participating in youth sports, 29% of young people already have MRI evidence of knee osteoarthritis.
Data source: The Alberta Youth Prevention in Early OA study, an ongoing prospective 200-subject longitudinal cohort study of the long-term consequences of sports-related knee injury.
Disclosures: The study is funded by the Canadian Institutes of Health Research and nonprofit organizations. The presenter reported having no financial conflicts.
Think twice before recommending partial meniscectomy
LAS VEGAS – Patients with knee osteoarthritis (OA) and a meniscal tear who underwent arthroscopic partial meniscectomy (APM) subsequently experienced accelerated structural progression of their OA, compared with those randomized to physical therapy alone in the randomized METEOR trial.
“In discussing treatment options for symptomatic meniscal tear, patients and providers must weigh the potential benefits and risks of arthroscopic partial meniscectomy, including this increased risk of structural progression,” Jamie E. Collins, PhD, said at the World Congress on Osteoarthritis.
The METEOR (Meniscal Tear in Osteoarthritis Research; NCT00597012) findings are clinically relevant because an estimated 14 million Americans have knee OA, and three-quarters of them also have MRI evidence of a meniscal tear, observed Dr. Collins, a senior statistician at the Orthopaedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, Boston.
A thorough physician-patient discussion also needs to mention that several large randomized trials have suggested that patients with meniscal tear and osteoarthritic changes experience similar pain relief with APM plus physical therapy (PT) as compared with PT alone, she added at the congress sponsored by the Osteoarthritis Research Society International.
The METEOR trial was a seven-center U.S. randomized trial of APM plus PT or PT alone in patients with MRI or radiographic evidence of OA changes, a meniscal tear on MRI, and mechanical knee symptoms. Dr. Collins reported on 176 randomized patients with baseline and 18-month follow-up MRIs read by a specialist musculoskeletal radiologist. This analysis excluded the 37 patients in the PT group who crossed over to APM within 6 months after randomization.
There was no significant difference between the two treatment groups in changes in bone marrow lesions or Hoffa-synovitis.
A secondary analysis that incorporated the 37 crossovers from PT to APM within 6 months showed similarly accelerated OA progression after arthroscopic surgery.
“Future work should focus on determining whether this accelerated structural progression is associated with changes in symptoms and ultimately with a higher risk of total knee replacement. In other words, is 2+ structural worsening something that’s noticeable or important for patients?” Dr. Collins concluded.
She reported having no financial conflicts regarding her study, which was sponsored by Brigham and Women’s Hospital.
LAS VEGAS – Patients with knee osteoarthritis (OA) and a meniscal tear who underwent arthroscopic partial meniscectomy (APM) subsequently experienced accelerated structural progression of their OA, compared with those randomized to physical therapy alone in the randomized METEOR trial.
“In discussing treatment options for symptomatic meniscal tear, patients and providers must weigh the potential benefits and risks of arthroscopic partial meniscectomy, including this increased risk of structural progression,” Jamie E. Collins, PhD, said at the World Congress on Osteoarthritis.
The METEOR (Meniscal Tear in Osteoarthritis Research; NCT00597012) findings are clinically relevant because an estimated 14 million Americans have knee OA, and three-quarters of them also have MRI evidence of a meniscal tear, observed Dr. Collins, a senior statistician at the Orthopaedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, Boston.
A thorough physician-patient discussion also needs to mention that several large randomized trials have suggested that patients with meniscal tear and osteoarthritic changes experience similar pain relief with APM plus physical therapy (PT) as compared with PT alone, she added at the congress sponsored by the Osteoarthritis Research Society International.
The METEOR trial was a seven-center U.S. randomized trial of APM plus PT or PT alone in patients with MRI or radiographic evidence of OA changes, a meniscal tear on MRI, and mechanical knee symptoms. Dr. Collins reported on 176 randomized patients with baseline and 18-month follow-up MRIs read by a specialist musculoskeletal radiologist. This analysis excluded the 37 patients in the PT group who crossed over to APM within 6 months after randomization.
There was no significant difference between the two treatment groups in changes in bone marrow lesions or Hoffa-synovitis.
A secondary analysis that incorporated the 37 crossovers from PT to APM within 6 months showed similarly accelerated OA progression after arthroscopic surgery.
“Future work should focus on determining whether this accelerated structural progression is associated with changes in symptoms and ultimately with a higher risk of total knee replacement. In other words, is 2+ structural worsening something that’s noticeable or important for patients?” Dr. Collins concluded.
She reported having no financial conflicts regarding her study, which was sponsored by Brigham and Women’s Hospital.
LAS VEGAS – Patients with knee osteoarthritis (OA) and a meniscal tear who underwent arthroscopic partial meniscectomy (APM) subsequently experienced accelerated structural progression of their OA, compared with those randomized to physical therapy alone in the randomized METEOR trial.
“In discussing treatment options for symptomatic meniscal tear, patients and providers must weigh the potential benefits and risks of arthroscopic partial meniscectomy, including this increased risk of structural progression,” Jamie E. Collins, PhD, said at the World Congress on Osteoarthritis.
The METEOR (Meniscal Tear in Osteoarthritis Research; NCT00597012) findings are clinically relevant because an estimated 14 million Americans have knee OA, and three-quarters of them also have MRI evidence of a meniscal tear, observed Dr. Collins, a senior statistician at the Orthopaedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, Boston.
A thorough physician-patient discussion also needs to mention that several large randomized trials have suggested that patients with meniscal tear and osteoarthritic changes experience similar pain relief with APM plus physical therapy (PT) as compared with PT alone, she added at the congress sponsored by the Osteoarthritis Research Society International.
The METEOR trial was a seven-center U.S. randomized trial of APM plus PT or PT alone in patients with MRI or radiographic evidence of OA changes, a meniscal tear on MRI, and mechanical knee symptoms. Dr. Collins reported on 176 randomized patients with baseline and 18-month follow-up MRIs read by a specialist musculoskeletal radiologist. This analysis excluded the 37 patients in the PT group who crossed over to APM within 6 months after randomization.
There was no significant difference between the two treatment groups in changes in bone marrow lesions or Hoffa-synovitis.
A secondary analysis that incorporated the 37 crossovers from PT to APM within 6 months showed similarly accelerated OA progression after arthroscopic surgery.
“Future work should focus on determining whether this accelerated structural progression is associated with changes in symptoms and ultimately with a higher risk of total knee replacement. In other words, is 2+ structural worsening something that’s noticeable or important for patients?” Dr. Collins concluded.
She reported having no financial conflicts regarding her study, which was sponsored by Brigham and Women’s Hospital.
AT OARSI 2017
Key clinical point:
Major finding: Surgically treated patients were 2.6 times more likely to demonstrate MRI evidence of structural disease progression at 18 months than those who received physical therapy alone.
Data source: This analysis from the multicenter METEOR trial included 176 patients with a symptomatic meniscal tear.
Disclosures: The presenter reported having no financial conflicts regarding her study, which was sponsored by Brigham and Women’s Hospital.
New evidence bisphosphonates may prevent OA
LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.
In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.
“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.
The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.
Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.
Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.
The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.
In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.
As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.
She reported having no financial conflicts regarding the NIH-sponsored study.
LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.
In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.
“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.
The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.
Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.
Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.
The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.
In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.
As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.
She reported having no financial conflicts regarding the NIH-sponsored study.
LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.
In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.
“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.
The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.
Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.
Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.
The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.
In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.
As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.
She reported having no financial conflicts regarding the NIH-sponsored study.
AT OARSI 2017
Key clinical point:
Major finding: Bisphosphonate users were 41% less likely to be in the group with the fastest trajectory of changes in bone shape known to be highly predictive of knee osteoarthritis.
Data source: This analysis of MRI-based changes in 3D bone shape of the knee over 4 years of follow-up included 1,071 female participants in the multicenter, prospective, observational Osteoarthritis Initiative.
Disclosures: The presenter reported having no financial conflicts regarding the NIH-sponsored study.
How bariatric surgery improves knee osteoarthritis
LAS VEGAS – Most of the improvement in knee pain that occurs following bariatric surgery in obese patients with knee osteoarthritis happens in the first month after surgery, well before the bulk of the weight loss takes place, Jonathan Samuels, MD, reported at the World Congress on Osteoarthritis.
This observation suggests that bariatric surgery’s mechanism of benefit in patients with knee osteoarthritis (OA) isn’t simply a matter of reduced mechanical load on the joints caused by a lessened weight burden, Dr. Samuels observed at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.
Indeed, his prospective study of 150 obese patients with comorbid knee OA points to metabolic factors as likely playing a key role.
“Post–bariatric surgery changes in inflammatory biomarkers, especially leptin, may help to explain the symptomatic relief of knee pain – and potential joint preservation,” said Dr. Samuels, a rheumatologist at New York University.
His study, featuring 2 years of follow-up to date, showed that bariatric surgery improved knee OA proportionate to the percentage of excess weight loss achieved. The greatest reduction in knee pain as well as the most profound weight loss occurred in the 35 patients who underwent gastric bypass and the 97 who opted for sleeve gastrectomy; patients who underwent laparoscopic adjustable gastric banding had more modest outcomes on both scores.
The disparate timing of the reductions in excess weight and knee pain was particularly eye catching. With all three forms of bariatric surgery, weight loss continued steadily for roughly the first 12 months. It then plateaued and was generally maintained at the new body mass index for the second 12 months.
In contrast, improvement in knee pain according to the validated Knee Injury and Osteoarthritis Outcome Score (KOOS) leveled out after just 1 month post surgery and was then sustained through 23 months. Levels of the inflammatory cytokines and adipokines interleukin-6, interleukin-1 receptor antagonist, and lipopolysaccharides were elevated at baseline but dropped steadily in concert with the reduction in excess body weight during the first 12 months after surgery. In contrast, levels of the anti-inflammatory cytokine sRAGE (soluble receptor for advanced glycation end products) were abnormally low prior to surgery but increased sharply for the first 3 months afterward before leveling off. And levels of serum leptin, which were roughly sevenfold greater than in normal controls at baseline, fell precipitously during the first month after bariatric surgery before plateauing, following the same pattern as the improvement in knee pain.
“This suggests that perhaps leptin is the key mediator in this OA population,” said Dr. Samuels.
Obese patients with knee OA are in a catch-22 situation. Obese individuals are at greatly increased lifetime risk of developing knee OA, and patients with chronic knee pain have a tough time losing weight.
“The treatments that might work with either obesity or knee pain alone often fail when both of these are present,” he observed.
That’s why bariatric surgery is becoming an increasingly popular treatment strategy in these patients. Sleeve gastrectomy, gastric bypass, and laparoscopic adjustable gastric banding are all Food and Drug Administration approved treatments for obesity in the presence of at least one qualifying comorbid condition, and knee OA qualifies.
Dr. Samuels reported having no financial conflicts regarding his study.
LAS VEGAS – Most of the improvement in knee pain that occurs following bariatric surgery in obese patients with knee osteoarthritis happens in the first month after surgery, well before the bulk of the weight loss takes place, Jonathan Samuels, MD, reported at the World Congress on Osteoarthritis.
This observation suggests that bariatric surgery’s mechanism of benefit in patients with knee osteoarthritis (OA) isn’t simply a matter of reduced mechanical load on the joints caused by a lessened weight burden, Dr. Samuels observed at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.
Indeed, his prospective study of 150 obese patients with comorbid knee OA points to metabolic factors as likely playing a key role.
“Post–bariatric surgery changes in inflammatory biomarkers, especially leptin, may help to explain the symptomatic relief of knee pain – and potential joint preservation,” said Dr. Samuels, a rheumatologist at New York University.
His study, featuring 2 years of follow-up to date, showed that bariatric surgery improved knee OA proportionate to the percentage of excess weight loss achieved. The greatest reduction in knee pain as well as the most profound weight loss occurred in the 35 patients who underwent gastric bypass and the 97 who opted for sleeve gastrectomy; patients who underwent laparoscopic adjustable gastric banding had more modest outcomes on both scores.
The disparate timing of the reductions in excess weight and knee pain was particularly eye catching. With all three forms of bariatric surgery, weight loss continued steadily for roughly the first 12 months. It then plateaued and was generally maintained at the new body mass index for the second 12 months.
In contrast, improvement in knee pain according to the validated Knee Injury and Osteoarthritis Outcome Score (KOOS) leveled out after just 1 month post surgery and was then sustained through 23 months. Levels of the inflammatory cytokines and adipokines interleukin-6, interleukin-1 receptor antagonist, and lipopolysaccharides were elevated at baseline but dropped steadily in concert with the reduction in excess body weight during the first 12 months after surgery. In contrast, levels of the anti-inflammatory cytokine sRAGE (soluble receptor for advanced glycation end products) were abnormally low prior to surgery but increased sharply for the first 3 months afterward before leveling off. And levels of serum leptin, which were roughly sevenfold greater than in normal controls at baseline, fell precipitously during the first month after bariatric surgery before plateauing, following the same pattern as the improvement in knee pain.
“This suggests that perhaps leptin is the key mediator in this OA population,” said Dr. Samuels.
Obese patients with knee OA are in a catch-22 situation. Obese individuals are at greatly increased lifetime risk of developing knee OA, and patients with chronic knee pain have a tough time losing weight.
“The treatments that might work with either obesity or knee pain alone often fail when both of these are present,” he observed.
That’s why bariatric surgery is becoming an increasingly popular treatment strategy in these patients. Sleeve gastrectomy, gastric bypass, and laparoscopic adjustable gastric banding are all Food and Drug Administration approved treatments for obesity in the presence of at least one qualifying comorbid condition, and knee OA qualifies.
Dr. Samuels reported having no financial conflicts regarding his study.
LAS VEGAS – Most of the improvement in knee pain that occurs following bariatric surgery in obese patients with knee osteoarthritis happens in the first month after surgery, well before the bulk of the weight loss takes place, Jonathan Samuels, MD, reported at the World Congress on Osteoarthritis.
This observation suggests that bariatric surgery’s mechanism of benefit in patients with knee osteoarthritis (OA) isn’t simply a matter of reduced mechanical load on the joints caused by a lessened weight burden, Dr. Samuels observed at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.
Indeed, his prospective study of 150 obese patients with comorbid knee OA points to metabolic factors as likely playing a key role.
“Post–bariatric surgery changes in inflammatory biomarkers, especially leptin, may help to explain the symptomatic relief of knee pain – and potential joint preservation,” said Dr. Samuels, a rheumatologist at New York University.
His study, featuring 2 years of follow-up to date, showed that bariatric surgery improved knee OA proportionate to the percentage of excess weight loss achieved. The greatest reduction in knee pain as well as the most profound weight loss occurred in the 35 patients who underwent gastric bypass and the 97 who opted for sleeve gastrectomy; patients who underwent laparoscopic adjustable gastric banding had more modest outcomes on both scores.
The disparate timing of the reductions in excess weight and knee pain was particularly eye catching. With all three forms of bariatric surgery, weight loss continued steadily for roughly the first 12 months. It then plateaued and was generally maintained at the new body mass index for the second 12 months.
In contrast, improvement in knee pain according to the validated Knee Injury and Osteoarthritis Outcome Score (KOOS) leveled out after just 1 month post surgery and was then sustained through 23 months. Levels of the inflammatory cytokines and adipokines interleukin-6, interleukin-1 receptor antagonist, and lipopolysaccharides were elevated at baseline but dropped steadily in concert with the reduction in excess body weight during the first 12 months after surgery. In contrast, levels of the anti-inflammatory cytokine sRAGE (soluble receptor for advanced glycation end products) were abnormally low prior to surgery but increased sharply for the first 3 months afterward before leveling off. And levels of serum leptin, which were roughly sevenfold greater than in normal controls at baseline, fell precipitously during the first month after bariatric surgery before plateauing, following the same pattern as the improvement in knee pain.
“This suggests that perhaps leptin is the key mediator in this OA population,” said Dr. Samuels.
Obese patients with knee OA are in a catch-22 situation. Obese individuals are at greatly increased lifetime risk of developing knee OA, and patients with chronic knee pain have a tough time losing weight.
“The treatments that might work with either obesity or knee pain alone often fail when both of these are present,” he observed.
That’s why bariatric surgery is becoming an increasingly popular treatment strategy in these patients. Sleeve gastrectomy, gastric bypass, and laparoscopic adjustable gastric banding are all Food and Drug Administration approved treatments for obesity in the presence of at least one qualifying comorbid condition, and knee OA qualifies.
Dr. Samuels reported having no financial conflicts regarding his study.
AT OARSI 2017
Key clinical point:
Major finding: Most of the improvement in knee pain – and most of the accompanying drop in serum leptin – happens in the first month following bariatric surgery, well before most weight loss has occurred.
Data source: A prospective observational study of 150 obese patients with knee osteoarthritis who underwent bariatric surgery.
Disclosures: The study presenter reported having no financial conflicts.
OARSI to FDA: Take osteoarthritis seriously
LAS VEGAS – The Osteoarthritis Research Society International has submitted a 103-page white paper to the Food and Drug Administration, the gist of which is captured in its title: “Osteoarthritis: A Serious Disease.”
The purpose of the voluminous white paper is to persuade FDA officials that osteoarthritis (OA) meets the agency’s formal definition of a serious disease for which there are currently no satisfactory treatments. That recognition would result in removal of current regulatory barriers to development of new structure-modifying treatments for OA, instead allowing such efforts to fall within the agency’s accelerated approval program, Marc C. Hochberg, MD, a coauthor of the white paper, explained at the World Congress on Osteoarthritis.
“FDA recognition of osteoarthritis as a serious disease would allow a pathway for approval of treatments for osteoarthritis without having to show that they reduce the incidence of total joint arthroplasty and possibly without having to show that a treatment reduces the progression of structural damage on plain radiographs,” according to Dr. Hochberg, professor of medicine, epidemiology, and public health and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.
OARSI would like to see novel investigational therapies be allowed to advance through the developmental pipeline on the basis of favorable changes in clinically relevant biomarkers – be they biochemical or imaging – as intermediate endpoints serving as surrogates for structural change endpoints and meaningful clinical outcomes.
There is an enormous unmet need for effective disease-modifying therapies for OA. Establishing a more flexible regulatory environment for drug development by designating OA as a serious disease is expected to rekindle pharmaceutical industry interest in developing such products, which at present is at an ebb, he continued at the congress sponsored by the Osteoarthritis Research Society International.
The FDA has defined a serious disease as “a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible if it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.”
The white paper makes the case that OA fits that description to a T. Dr. Hochberg said the big picture regarding OA as described in the white paper is this: It’s the most common form of arthritis, affecting more than 250 million people worldwide. And its costs approach 2% of the gross national product in the United States and other developed countries.
“Osteoarthritis accounts for more functional limitation, work loss, and physical disability than any other chronic disease, including cardiovascular disease and chronic obstructive pulmonary disease,” the rheumatologist said.
The white paper cites published data in support of these and other key points. At OARSI 2017, Dr. Hochberg presented highlights from the white paper, submitted to the FDA in December 2016:
• OA prevalence is relentlessly climbing. The Centers for Disease Control and Prevention put the U.S. prevalence of OA at 46 million in 2004 and has projected that it will reach 63 million in 2020 and 78 million Americans by 2040. The rise is being driven by the aging of the baby boomers, the obesity epidemic, predisposing physical injuries, and sedentary behavior.
• OA is expensive for patients and society. The combined direct medical costs and indirect costs stemming from lost earnings from OA amount to an estimated $461 billion annually in the United States.
• OA exacts a steep toll in years lived with disability (YLD). Estimated YLD from OA jumped by 75% during 1990-2013. This increase in YLD was exceeded only by dementia at 84% and diabetes at 135%. OA accounts for 1.6% of overall YLD in the United States, a rate comparable to ischemic heart disease at 1.63% and more than twice that for rheumatoid arthritis at 0.68%.
• Comorbidities are the rule. Various studies have estimated that 59%-87% of adults with OA have at least one additional significant chronic condition. The median number is two. One-third of OA patients have four or more additional comorbid conditions. The most common are cardiovascular disease, diabetes, obesity, metabolic syndrome, depression, anxiety, and falls and fractures.
• No effective treatments exist. There are no approved drugs that can prevent or even slow progression of OA to the point where total joint replacement is needed. Current medications are focused on pain relief and maintenance of functional independence. But these drugs are associated with significant risks of life-threatening side effects. NSAIDs have been linked to increased risk of cardiovascular events, GI bleeding, chronic kidney disease, and heart failure. And while opioids provide a small benefit in terms of pain relief, this is outweighed by the associated risks of falls, fractures, dependence, overdose, and death. All of these risks are accentuated in the presence of the common comorbid conditions associated with OA.
• OA increases the risk of dying prematurely. In a meta-analysis of individual patient data from the Multicenter Osteoarthritis Study and the Johnston County (N.C.) Osteoarthritis Project conducted specifically for the white paper, investigators determined that OA was associated with a 23% increase in the risk of death independent of age, race, and sex. This excess mortality is attributable in part to the presence of the metabolic syndrome and other commonly comorbid conditions, reduced physical activity because of OA disability, and the use of NSAIDs and opioid analgesics for symptomatic control.
The OARSI initiative is supported by EMD Serono, Fidia Pharma, Flexion Therapeutics, Nordic Biosciences, and Spinifex. Dr. Hochberg reported having numerous financial relationships with industry.
LAS VEGAS – The Osteoarthritis Research Society International has submitted a 103-page white paper to the Food and Drug Administration, the gist of which is captured in its title: “Osteoarthritis: A Serious Disease.”
The purpose of the voluminous white paper is to persuade FDA officials that osteoarthritis (OA) meets the agency’s formal definition of a serious disease for which there are currently no satisfactory treatments. That recognition would result in removal of current regulatory barriers to development of new structure-modifying treatments for OA, instead allowing such efforts to fall within the agency’s accelerated approval program, Marc C. Hochberg, MD, a coauthor of the white paper, explained at the World Congress on Osteoarthritis.
“FDA recognition of osteoarthritis as a serious disease would allow a pathway for approval of treatments for osteoarthritis without having to show that they reduce the incidence of total joint arthroplasty and possibly without having to show that a treatment reduces the progression of structural damage on plain radiographs,” according to Dr. Hochberg, professor of medicine, epidemiology, and public health and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.
OARSI would like to see novel investigational therapies be allowed to advance through the developmental pipeline on the basis of favorable changes in clinically relevant biomarkers – be they biochemical or imaging – as intermediate endpoints serving as surrogates for structural change endpoints and meaningful clinical outcomes.
There is an enormous unmet need for effective disease-modifying therapies for OA. Establishing a more flexible regulatory environment for drug development by designating OA as a serious disease is expected to rekindle pharmaceutical industry interest in developing such products, which at present is at an ebb, he continued at the congress sponsored by the Osteoarthritis Research Society International.
The FDA has defined a serious disease as “a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible if it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.”
The white paper makes the case that OA fits that description to a T. Dr. Hochberg said the big picture regarding OA as described in the white paper is this: It’s the most common form of arthritis, affecting more than 250 million people worldwide. And its costs approach 2% of the gross national product in the United States and other developed countries.
“Osteoarthritis accounts for more functional limitation, work loss, and physical disability than any other chronic disease, including cardiovascular disease and chronic obstructive pulmonary disease,” the rheumatologist said.
The white paper cites published data in support of these and other key points. At OARSI 2017, Dr. Hochberg presented highlights from the white paper, submitted to the FDA in December 2016:
• OA prevalence is relentlessly climbing. The Centers for Disease Control and Prevention put the U.S. prevalence of OA at 46 million in 2004 and has projected that it will reach 63 million in 2020 and 78 million Americans by 2040. The rise is being driven by the aging of the baby boomers, the obesity epidemic, predisposing physical injuries, and sedentary behavior.
• OA is expensive for patients and society. The combined direct medical costs and indirect costs stemming from lost earnings from OA amount to an estimated $461 billion annually in the United States.
• OA exacts a steep toll in years lived with disability (YLD). Estimated YLD from OA jumped by 75% during 1990-2013. This increase in YLD was exceeded only by dementia at 84% and diabetes at 135%. OA accounts for 1.6% of overall YLD in the United States, a rate comparable to ischemic heart disease at 1.63% and more than twice that for rheumatoid arthritis at 0.68%.
• Comorbidities are the rule. Various studies have estimated that 59%-87% of adults with OA have at least one additional significant chronic condition. The median number is two. One-third of OA patients have four or more additional comorbid conditions. The most common are cardiovascular disease, diabetes, obesity, metabolic syndrome, depression, anxiety, and falls and fractures.
• No effective treatments exist. There are no approved drugs that can prevent or even slow progression of OA to the point where total joint replacement is needed. Current medications are focused on pain relief and maintenance of functional independence. But these drugs are associated with significant risks of life-threatening side effects. NSAIDs have been linked to increased risk of cardiovascular events, GI bleeding, chronic kidney disease, and heart failure. And while opioids provide a small benefit in terms of pain relief, this is outweighed by the associated risks of falls, fractures, dependence, overdose, and death. All of these risks are accentuated in the presence of the common comorbid conditions associated with OA.
• OA increases the risk of dying prematurely. In a meta-analysis of individual patient data from the Multicenter Osteoarthritis Study and the Johnston County (N.C.) Osteoarthritis Project conducted specifically for the white paper, investigators determined that OA was associated with a 23% increase in the risk of death independent of age, race, and sex. This excess mortality is attributable in part to the presence of the metabolic syndrome and other commonly comorbid conditions, reduced physical activity because of OA disability, and the use of NSAIDs and opioid analgesics for symptomatic control.
The OARSI initiative is supported by EMD Serono, Fidia Pharma, Flexion Therapeutics, Nordic Biosciences, and Spinifex. Dr. Hochberg reported having numerous financial relationships with industry.
LAS VEGAS – The Osteoarthritis Research Society International has submitted a 103-page white paper to the Food and Drug Administration, the gist of which is captured in its title: “Osteoarthritis: A Serious Disease.”
The purpose of the voluminous white paper is to persuade FDA officials that osteoarthritis (OA) meets the agency’s formal definition of a serious disease for which there are currently no satisfactory treatments. That recognition would result in removal of current regulatory barriers to development of new structure-modifying treatments for OA, instead allowing such efforts to fall within the agency’s accelerated approval program, Marc C. Hochberg, MD, a coauthor of the white paper, explained at the World Congress on Osteoarthritis.
“FDA recognition of osteoarthritis as a serious disease would allow a pathway for approval of treatments for osteoarthritis without having to show that they reduce the incidence of total joint arthroplasty and possibly without having to show that a treatment reduces the progression of structural damage on plain radiographs,” according to Dr. Hochberg, professor of medicine, epidemiology, and public health and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.
OARSI would like to see novel investigational therapies be allowed to advance through the developmental pipeline on the basis of favorable changes in clinically relevant biomarkers – be they biochemical or imaging – as intermediate endpoints serving as surrogates for structural change endpoints and meaningful clinical outcomes.
There is an enormous unmet need for effective disease-modifying therapies for OA. Establishing a more flexible regulatory environment for drug development by designating OA as a serious disease is expected to rekindle pharmaceutical industry interest in developing such products, which at present is at an ebb, he continued at the congress sponsored by the Osteoarthritis Research Society International.
The FDA has defined a serious disease as “a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible if it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.”
The white paper makes the case that OA fits that description to a T. Dr. Hochberg said the big picture regarding OA as described in the white paper is this: It’s the most common form of arthritis, affecting more than 250 million people worldwide. And its costs approach 2% of the gross national product in the United States and other developed countries.
“Osteoarthritis accounts for more functional limitation, work loss, and physical disability than any other chronic disease, including cardiovascular disease and chronic obstructive pulmonary disease,” the rheumatologist said.
The white paper cites published data in support of these and other key points. At OARSI 2017, Dr. Hochberg presented highlights from the white paper, submitted to the FDA in December 2016:
• OA prevalence is relentlessly climbing. The Centers for Disease Control and Prevention put the U.S. prevalence of OA at 46 million in 2004 and has projected that it will reach 63 million in 2020 and 78 million Americans by 2040. The rise is being driven by the aging of the baby boomers, the obesity epidemic, predisposing physical injuries, and sedentary behavior.
• OA is expensive for patients and society. The combined direct medical costs and indirect costs stemming from lost earnings from OA amount to an estimated $461 billion annually in the United States.
• OA exacts a steep toll in years lived with disability (YLD). Estimated YLD from OA jumped by 75% during 1990-2013. This increase in YLD was exceeded only by dementia at 84% and diabetes at 135%. OA accounts for 1.6% of overall YLD in the United States, a rate comparable to ischemic heart disease at 1.63% and more than twice that for rheumatoid arthritis at 0.68%.
• Comorbidities are the rule. Various studies have estimated that 59%-87% of adults with OA have at least one additional significant chronic condition. The median number is two. One-third of OA patients have four or more additional comorbid conditions. The most common are cardiovascular disease, diabetes, obesity, metabolic syndrome, depression, anxiety, and falls and fractures.
• No effective treatments exist. There are no approved drugs that can prevent or even slow progression of OA to the point where total joint replacement is needed. Current medications are focused on pain relief and maintenance of functional independence. But these drugs are associated with significant risks of life-threatening side effects. NSAIDs have been linked to increased risk of cardiovascular events, GI bleeding, chronic kidney disease, and heart failure. And while opioids provide a small benefit in terms of pain relief, this is outweighed by the associated risks of falls, fractures, dependence, overdose, and death. All of these risks are accentuated in the presence of the common comorbid conditions associated with OA.
• OA increases the risk of dying prematurely. In a meta-analysis of individual patient data from the Multicenter Osteoarthritis Study and the Johnston County (N.C.) Osteoarthritis Project conducted specifically for the white paper, investigators determined that OA was associated with a 23% increase in the risk of death independent of age, race, and sex. This excess mortality is attributable in part to the presence of the metabolic syndrome and other commonly comorbid conditions, reduced physical activity because of OA disability, and the use of NSAIDs and opioid analgesics for symptomatic control.
The OARSI initiative is supported by EMD Serono, Fidia Pharma, Flexion Therapeutics, Nordic Biosciences, and Spinifex. Dr. Hochberg reported having numerous financial relationships with industry.
AT OARSI 2017
Lifetime risk of hand OA comes close to 40%
Almost 40% of Americans can expect to develop hand osteoarthritis (OA) in their lifetimes, according to an analysis involving participants from an ongoing population-based, prospective cohort study.
The overall risk, 39.8%, is based on data from 2,218 eligible subjects in the Johnston County Osteoarthritis Project, but there is significant variation among various subgroups, said Jin Qin, ScD, of the Centers for Disease Control and Prevention, and her associates (Arthritis Rheumatol. 2017 May 4. doi: 10.1002/art.40097).
This report is the first to estimate the lifetime risk of symptomatic hand OA, they noted, and “given the aging population and increasing life expectancy in the United States, it is reasonable to expect that more Americans will be affected by this painful and debilitating condition in the years to come.”
The study was funded by the CDC and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators did not include any disclosures in the report.
Almost 40% of Americans can expect to develop hand osteoarthritis (OA) in their lifetimes, according to an analysis involving participants from an ongoing population-based, prospective cohort study.
The overall risk, 39.8%, is based on data from 2,218 eligible subjects in the Johnston County Osteoarthritis Project, but there is significant variation among various subgroups, said Jin Qin, ScD, of the Centers for Disease Control and Prevention, and her associates (Arthritis Rheumatol. 2017 May 4. doi: 10.1002/art.40097).
This report is the first to estimate the lifetime risk of symptomatic hand OA, they noted, and “given the aging population and increasing life expectancy in the United States, it is reasonable to expect that more Americans will be affected by this painful and debilitating condition in the years to come.”
The study was funded by the CDC and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators did not include any disclosures in the report.
Almost 40% of Americans can expect to develop hand osteoarthritis (OA) in their lifetimes, according to an analysis involving participants from an ongoing population-based, prospective cohort study.
The overall risk, 39.8%, is based on data from 2,218 eligible subjects in the Johnston County Osteoarthritis Project, but there is significant variation among various subgroups, said Jin Qin, ScD, of the Centers for Disease Control and Prevention, and her associates (Arthritis Rheumatol. 2017 May 4. doi: 10.1002/art.40097).
This report is the first to estimate the lifetime risk of symptomatic hand OA, they noted, and “given the aging population and increasing life expectancy in the United States, it is reasonable to expect that more Americans will be affected by this painful and debilitating condition in the years to come.”
The study was funded by the CDC and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The investigators did not include any disclosures in the report.
FROM ARTHRITIS & RHEUMATOLOGY
No increase in hand osteoarthritis seen in Sjögren’s syndrome
LAS VEGAS – Patients with Sjögren’s syndrome do not have an increased prevalence of hand osteoarthritis, but they are strongly predisposed to have a history of hypothyroidism, Jeremie Sellam, MD, reported at the World Congress on Osteoarthritis.
Both of these findings in his small case-control study were unexpected, he added at the congress sponsored by the Osteoarthritis Research Society International.
“In my clinical practice, I’ve had the impression that patients with Sjögren’s syndrome exhibit more hand osteoarthritis. Since this is an autoimmune disease and osteoarthritis is characterized by persistent low-grade inflammation, we hypothesized that patients with Sjögren’s syndrome would have a higher rate of hand osteoarthritis. But our hypothesis was not confirmed. We did not find any evidence of an increased prevalence of hand osteoarthritis in Sjögren’s syndrome patients,” said Dr. Sellam, a rheumatologist at Saint Antoine Hospital in Paris.
The study included 34 women with primary Sjögren’s syndrome according to the 2002 American-European Consensus Group criteria and 54 female controls with sicca syndrome but no autoantibodies and no Sjögren’s syndrome. All subjects were evaluated at a specialized tertiary Sjögren’s syndrome clinic. The controls were referred there to ascertain whether they had Sjögren’s syndrome.
Among the Sjögren’s syndrome patients, 41% had radiographic evidence of hand osteoarthritis, 12% had symptomatic hand osteoarthritis, and 9% had erosive hand osteoarthritis. In the sicca syndrome–only patients, the rates were similar at 52%, 28%, and 9%, respectively.
Looking for commonalities and differences between the Sjögren’s syndrome patients and controls, Dr. Sellam and his coinvestigators noted that the Sjögren’s syndrome patients were significantly older, with an average age of 64 years, compared with 48.5 years in the controls.
Impressively, two-thirds of the 15 Sjögren’s syndrome patients with hand osteoarthritis had a history of hypothyroidism, compared with just 15% of the 27 non-autoimmune sicca syndrome patients with hand osteoarthritis and one-quarter of the Sjögren’s syndrome patients without hand osteoarthritis. This suggests a possible interaction between Sjögren’s syndrome, hand osteoarthritis, and a history of hypothyroidism which merits further study, according to the rheumatologist.
Because of the relatively small patient numbers in the French study, Dr. Sellam and coworkers ran a crosscheck with data from the Framingham Osteoarthritis Study and found hand osteoarthritis prevalence rates comparable to their own findings. For example, the prevalences of radiographic and erosive hand osteoarthritis in the French Sjögren’s syndrome and non-autoimmune sicca syndrome groups were similar to the 44% and 10% figures, respectively, in the general population of age-matched Framingham women (Ann Rheum Dis. 2011 Sep;70[9]:1581-6).
He reported having no financial conflicts regarding his study, which was conducted free of commercial support.
LAS VEGAS – Patients with Sjögren’s syndrome do not have an increased prevalence of hand osteoarthritis, but they are strongly predisposed to have a history of hypothyroidism, Jeremie Sellam, MD, reported at the World Congress on Osteoarthritis.
Both of these findings in his small case-control study were unexpected, he added at the congress sponsored by the Osteoarthritis Research Society International.
“In my clinical practice, I’ve had the impression that patients with Sjögren’s syndrome exhibit more hand osteoarthritis. Since this is an autoimmune disease and osteoarthritis is characterized by persistent low-grade inflammation, we hypothesized that patients with Sjögren’s syndrome would have a higher rate of hand osteoarthritis. But our hypothesis was not confirmed. We did not find any evidence of an increased prevalence of hand osteoarthritis in Sjögren’s syndrome patients,” said Dr. Sellam, a rheumatologist at Saint Antoine Hospital in Paris.
The study included 34 women with primary Sjögren’s syndrome according to the 2002 American-European Consensus Group criteria and 54 female controls with sicca syndrome but no autoantibodies and no Sjögren’s syndrome. All subjects were evaluated at a specialized tertiary Sjögren’s syndrome clinic. The controls were referred there to ascertain whether they had Sjögren’s syndrome.
Among the Sjögren’s syndrome patients, 41% had radiographic evidence of hand osteoarthritis, 12% had symptomatic hand osteoarthritis, and 9% had erosive hand osteoarthritis. In the sicca syndrome–only patients, the rates were similar at 52%, 28%, and 9%, respectively.
Looking for commonalities and differences between the Sjögren’s syndrome patients and controls, Dr. Sellam and his coinvestigators noted that the Sjögren’s syndrome patients were significantly older, with an average age of 64 years, compared with 48.5 years in the controls.
Impressively, two-thirds of the 15 Sjögren’s syndrome patients with hand osteoarthritis had a history of hypothyroidism, compared with just 15% of the 27 non-autoimmune sicca syndrome patients with hand osteoarthritis and one-quarter of the Sjögren’s syndrome patients without hand osteoarthritis. This suggests a possible interaction between Sjögren’s syndrome, hand osteoarthritis, and a history of hypothyroidism which merits further study, according to the rheumatologist.
Because of the relatively small patient numbers in the French study, Dr. Sellam and coworkers ran a crosscheck with data from the Framingham Osteoarthritis Study and found hand osteoarthritis prevalence rates comparable to their own findings. For example, the prevalences of radiographic and erosive hand osteoarthritis in the French Sjögren’s syndrome and non-autoimmune sicca syndrome groups were similar to the 44% and 10% figures, respectively, in the general population of age-matched Framingham women (Ann Rheum Dis. 2011 Sep;70[9]:1581-6).
He reported having no financial conflicts regarding his study, which was conducted free of commercial support.
LAS VEGAS – Patients with Sjögren’s syndrome do not have an increased prevalence of hand osteoarthritis, but they are strongly predisposed to have a history of hypothyroidism, Jeremie Sellam, MD, reported at the World Congress on Osteoarthritis.
Both of these findings in his small case-control study were unexpected, he added at the congress sponsored by the Osteoarthritis Research Society International.
“In my clinical practice, I’ve had the impression that patients with Sjögren’s syndrome exhibit more hand osteoarthritis. Since this is an autoimmune disease and osteoarthritis is characterized by persistent low-grade inflammation, we hypothesized that patients with Sjögren’s syndrome would have a higher rate of hand osteoarthritis. But our hypothesis was not confirmed. We did not find any evidence of an increased prevalence of hand osteoarthritis in Sjögren’s syndrome patients,” said Dr. Sellam, a rheumatologist at Saint Antoine Hospital in Paris.
The study included 34 women with primary Sjögren’s syndrome according to the 2002 American-European Consensus Group criteria and 54 female controls with sicca syndrome but no autoantibodies and no Sjögren’s syndrome. All subjects were evaluated at a specialized tertiary Sjögren’s syndrome clinic. The controls were referred there to ascertain whether they had Sjögren’s syndrome.
Among the Sjögren’s syndrome patients, 41% had radiographic evidence of hand osteoarthritis, 12% had symptomatic hand osteoarthritis, and 9% had erosive hand osteoarthritis. In the sicca syndrome–only patients, the rates were similar at 52%, 28%, and 9%, respectively.
Looking for commonalities and differences between the Sjögren’s syndrome patients and controls, Dr. Sellam and his coinvestigators noted that the Sjögren’s syndrome patients were significantly older, with an average age of 64 years, compared with 48.5 years in the controls.
Impressively, two-thirds of the 15 Sjögren’s syndrome patients with hand osteoarthritis had a history of hypothyroidism, compared with just 15% of the 27 non-autoimmune sicca syndrome patients with hand osteoarthritis and one-quarter of the Sjögren’s syndrome patients without hand osteoarthritis. This suggests a possible interaction between Sjögren’s syndrome, hand osteoarthritis, and a history of hypothyroidism which merits further study, according to the rheumatologist.
Because of the relatively small patient numbers in the French study, Dr. Sellam and coworkers ran a crosscheck with data from the Framingham Osteoarthritis Study and found hand osteoarthritis prevalence rates comparable to their own findings. For example, the prevalences of radiographic and erosive hand osteoarthritis in the French Sjögren’s syndrome and non-autoimmune sicca syndrome groups were similar to the 44% and 10% figures, respectively, in the general population of age-matched Framingham women (Ann Rheum Dis. 2011 Sep;70[9]:1581-6).
He reported having no financial conflicts regarding his study, which was conducted free of commercial support.
AT OARSI 2017
Key clinical point:
Major finding: Nine percent of women with Sjögren’s syndrome had erosive hand osteoarthritis, a prevalence identical to that in a group with non-autoimmune sicca syndrome only.
Data source: This case-control study included 34 women with Sjögren’s syndrome and 54 women with non-autoimmune sicca syndrome.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was conducted free of commercial support.
Adalimumab strikes out for hand osteoarthritis
LAS VEGAS – Adalimumab proved no better than placebo for the treatment of erosive hand osteoarthritis in the double-blind, placebo-controlled, randomized HUMOR trial, throwing cold water on hopes that a disease-modifying treatment for osteoarthritis might at long last have been found.
“This randomized controlled trial demonstrated that subcutaneous adalimumab at 40 mg every other week was no different from placebo for alleviation of pain, synovitis, or bone marrow lesions in patients with erosive hand osteoarthritis presenting with MRI-detected synovitis. This suggests that pain and inflammation are not responsive to TNF [tumor necrosis factor] inhibition in this patient population,” Dawn Aitken, PhD, declared at the World Congress on Osteoarthritis.
The HUMOR (Humira for Erosive Hand Osteoarthritis) trial was a single-center, crossover study that included 43 patients who met American College of Rheumatology criteria for hand OA, with pain scores greater than 50 on a 100-point visual analog scale, morning stiffness lasting for more than 30 minutes, radiographic evidence of erosive hand OA, and an MRI showing synovitis in painful hand joints. Participants received 12 weeks of therapy with either adalimumab (Humira) or placebo, then were crossed over to the other study arm for another 12 weeks following an 8-week washout period, she explained at the congress sponsored by the Osteoarthritis Research Society International.
The primary endpoint was change in the visual analog pain score over the course of 12 weeks of therapy. Scores dropped by an average of 3.0 points from a mean baseline of 63.6 with adalimumab and by 0.7 points with placebo. That between-group difference wasn’t statistically significant, nor were those modest reductions clinically meaningful. By convention, a clinically meaningful treatment result requires at least a 15-point improvement on the self-assessed pain scale, noted Dr. Aitken of the University of Tasmania in Hobart, Australia.
It made no difference which treatment arm came first.
“There was absolutely no placebo effect,” she said.
The study proved negative for all prespecified secondary endpoints, too. These included change in the Australian/Canadian Hand OA Index pain, function, and stiffness subscales, as well as change in bone marrow lesions and synovitis. A mere 12% of patients showed improvement in synovitis scores with adalimumab, as did 10% on placebo. Five percent of the adalimumab group and 7% on placebo showed improvement in bone marrow lesion scores.
The proinflammatory cytokine TNF-alpha has been shown to play a key role in OA development and progression. However, several prior studies failed to show a benefit for anti-TNF therapy in terms of reducing pain in hand OA patients, although in one of those negative studies, a post hoc analysis found that adalimumab halted erosive progression in the subset of interphalangeal joints with palpable soft tissue swelling at baseline (Ann Rheum Dis. 2012 Jun;71[6]:891-8).
Also, earlier in the session at OARSI 2017 at which Dr. Aitken presented the negative HUMOR trial data, Margreet Kloppenburg, MD, presented the results of a 1-year, multicenter, double-blind, placebo-controlled European trial of etanercept (Enbrel) in 68 patients with erosive hand OA. There was no significant difference between the etanercept and placebo groups in the primary study endpoint, which was change in visual analog pain scores at 24 weeks, nor was there a difference at 1 year.
However, there was a positive signal: In a subgroup analysis confined to the patients with inflammatory joints, the use of etanercept was associated with less structural damage of those joints over time as assessed using the quantitative Ghent University Scoring System, or GUSS, according to Dr. Kloppenburg, professor of rheumatology at Leiden (the Netherlands) University.
The emphatically negative results of the HUMOR trial were greeted with dismay by several disappointed audience members. They raised questions: Might a study featuring more than 12 weeks of treatment have brought positive results? How about a larger study? Why no placebo effect, given that patients were receiving injections? Is this area of investigation of TNF-inhibitor therapy now a dead end? Or could adalimumab and etanercept have differential efficacy in hand OA, even though they are both TNF inhibitors?
Dr. Aitken had an answer for every question.
“I think our study was big enough based on our power calculations to detect a difference of 15 mm on a visual analog scale, which is a clinically important difference. And that’s what we should be chasing in OA, that big effect. Patients are not going to be interested in a treatment that improves their pain by 5 mm,” she said.
As for the possibility that 12 weeks of adalimumab might have been too short to see a treatment effect, Dr. Aitken noted that anti-TNF therapy in rheumatoid arthritis brings a rapid response.
“Ideally, if you did have a disease-modifying drug for osteoarthritis you would want it to have a relatively quick response for pain; if patients aren’t seeing an effect after 3 months they might be less interested in taking it,” she continued.
Also, studies with a crossover design, like HUMOR, are known to have a much smaller placebo effect because patients know that at some point they’re certain to receive the active agent, Dr. Aitken observed.
As for the possibility that etanercept might be effective for erosive hand OA, while adalimumab is not, one physician commented, “That’s really scraping the bottom of the barrel.”
The HUMOR trial was sponsored by AbbVie. Dr. Aitken reported having no financial conflicts.
LAS VEGAS – Adalimumab proved no better than placebo for the treatment of erosive hand osteoarthritis in the double-blind, placebo-controlled, randomized HUMOR trial, throwing cold water on hopes that a disease-modifying treatment for osteoarthritis might at long last have been found.
“This randomized controlled trial demonstrated that subcutaneous adalimumab at 40 mg every other week was no different from placebo for alleviation of pain, synovitis, or bone marrow lesions in patients with erosive hand osteoarthritis presenting with MRI-detected synovitis. This suggests that pain and inflammation are not responsive to TNF [tumor necrosis factor] inhibition in this patient population,” Dawn Aitken, PhD, declared at the World Congress on Osteoarthritis.
The HUMOR (Humira for Erosive Hand Osteoarthritis) trial was a single-center, crossover study that included 43 patients who met American College of Rheumatology criteria for hand OA, with pain scores greater than 50 on a 100-point visual analog scale, morning stiffness lasting for more than 30 minutes, radiographic evidence of erosive hand OA, and an MRI showing synovitis in painful hand joints. Participants received 12 weeks of therapy with either adalimumab (Humira) or placebo, then were crossed over to the other study arm for another 12 weeks following an 8-week washout period, she explained at the congress sponsored by the Osteoarthritis Research Society International.
The primary endpoint was change in the visual analog pain score over the course of 12 weeks of therapy. Scores dropped by an average of 3.0 points from a mean baseline of 63.6 with adalimumab and by 0.7 points with placebo. That between-group difference wasn’t statistically significant, nor were those modest reductions clinically meaningful. By convention, a clinically meaningful treatment result requires at least a 15-point improvement on the self-assessed pain scale, noted Dr. Aitken of the University of Tasmania in Hobart, Australia.
It made no difference which treatment arm came first.
“There was absolutely no placebo effect,” she said.
The study proved negative for all prespecified secondary endpoints, too. These included change in the Australian/Canadian Hand OA Index pain, function, and stiffness subscales, as well as change in bone marrow lesions and synovitis. A mere 12% of patients showed improvement in synovitis scores with adalimumab, as did 10% on placebo. Five percent of the adalimumab group and 7% on placebo showed improvement in bone marrow lesion scores.
The proinflammatory cytokine TNF-alpha has been shown to play a key role in OA development and progression. However, several prior studies failed to show a benefit for anti-TNF therapy in terms of reducing pain in hand OA patients, although in one of those negative studies, a post hoc analysis found that adalimumab halted erosive progression in the subset of interphalangeal joints with palpable soft tissue swelling at baseline (Ann Rheum Dis. 2012 Jun;71[6]:891-8).
Also, earlier in the session at OARSI 2017 at which Dr. Aitken presented the negative HUMOR trial data, Margreet Kloppenburg, MD, presented the results of a 1-year, multicenter, double-blind, placebo-controlled European trial of etanercept (Enbrel) in 68 patients with erosive hand OA. There was no significant difference between the etanercept and placebo groups in the primary study endpoint, which was change in visual analog pain scores at 24 weeks, nor was there a difference at 1 year.
However, there was a positive signal: In a subgroup analysis confined to the patients with inflammatory joints, the use of etanercept was associated with less structural damage of those joints over time as assessed using the quantitative Ghent University Scoring System, or GUSS, according to Dr. Kloppenburg, professor of rheumatology at Leiden (the Netherlands) University.
The emphatically negative results of the HUMOR trial were greeted with dismay by several disappointed audience members. They raised questions: Might a study featuring more than 12 weeks of treatment have brought positive results? How about a larger study? Why no placebo effect, given that patients were receiving injections? Is this area of investigation of TNF-inhibitor therapy now a dead end? Or could adalimumab and etanercept have differential efficacy in hand OA, even though they are both TNF inhibitors?
Dr. Aitken had an answer for every question.
“I think our study was big enough based on our power calculations to detect a difference of 15 mm on a visual analog scale, which is a clinically important difference. And that’s what we should be chasing in OA, that big effect. Patients are not going to be interested in a treatment that improves their pain by 5 mm,” she said.
As for the possibility that 12 weeks of adalimumab might have been too short to see a treatment effect, Dr. Aitken noted that anti-TNF therapy in rheumatoid arthritis brings a rapid response.
“Ideally, if you did have a disease-modifying drug for osteoarthritis you would want it to have a relatively quick response for pain; if patients aren’t seeing an effect after 3 months they might be less interested in taking it,” she continued.
Also, studies with a crossover design, like HUMOR, are known to have a much smaller placebo effect because patients know that at some point they’re certain to receive the active agent, Dr. Aitken observed.
As for the possibility that etanercept might be effective for erosive hand OA, while adalimumab is not, one physician commented, “That’s really scraping the bottom of the barrel.”
The HUMOR trial was sponsored by AbbVie. Dr. Aitken reported having no financial conflicts.
LAS VEGAS – Adalimumab proved no better than placebo for the treatment of erosive hand osteoarthritis in the double-blind, placebo-controlled, randomized HUMOR trial, throwing cold water on hopes that a disease-modifying treatment for osteoarthritis might at long last have been found.
“This randomized controlled trial demonstrated that subcutaneous adalimumab at 40 mg every other week was no different from placebo for alleviation of pain, synovitis, or bone marrow lesions in patients with erosive hand osteoarthritis presenting with MRI-detected synovitis. This suggests that pain and inflammation are not responsive to TNF [tumor necrosis factor] inhibition in this patient population,” Dawn Aitken, PhD, declared at the World Congress on Osteoarthritis.
The HUMOR (Humira for Erosive Hand Osteoarthritis) trial was a single-center, crossover study that included 43 patients who met American College of Rheumatology criteria for hand OA, with pain scores greater than 50 on a 100-point visual analog scale, morning stiffness lasting for more than 30 minutes, radiographic evidence of erosive hand OA, and an MRI showing synovitis in painful hand joints. Participants received 12 weeks of therapy with either adalimumab (Humira) or placebo, then were crossed over to the other study arm for another 12 weeks following an 8-week washout period, she explained at the congress sponsored by the Osteoarthritis Research Society International.
The primary endpoint was change in the visual analog pain score over the course of 12 weeks of therapy. Scores dropped by an average of 3.0 points from a mean baseline of 63.6 with adalimumab and by 0.7 points with placebo. That between-group difference wasn’t statistically significant, nor were those modest reductions clinically meaningful. By convention, a clinically meaningful treatment result requires at least a 15-point improvement on the self-assessed pain scale, noted Dr. Aitken of the University of Tasmania in Hobart, Australia.
It made no difference which treatment arm came first.
“There was absolutely no placebo effect,” she said.
The study proved negative for all prespecified secondary endpoints, too. These included change in the Australian/Canadian Hand OA Index pain, function, and stiffness subscales, as well as change in bone marrow lesions and synovitis. A mere 12% of patients showed improvement in synovitis scores with adalimumab, as did 10% on placebo. Five percent of the adalimumab group and 7% on placebo showed improvement in bone marrow lesion scores.
The proinflammatory cytokine TNF-alpha has been shown to play a key role in OA development and progression. However, several prior studies failed to show a benefit for anti-TNF therapy in terms of reducing pain in hand OA patients, although in one of those negative studies, a post hoc analysis found that adalimumab halted erosive progression in the subset of interphalangeal joints with palpable soft tissue swelling at baseline (Ann Rheum Dis. 2012 Jun;71[6]:891-8).
Also, earlier in the session at OARSI 2017 at which Dr. Aitken presented the negative HUMOR trial data, Margreet Kloppenburg, MD, presented the results of a 1-year, multicenter, double-blind, placebo-controlled European trial of etanercept (Enbrel) in 68 patients with erosive hand OA. There was no significant difference between the etanercept and placebo groups in the primary study endpoint, which was change in visual analog pain scores at 24 weeks, nor was there a difference at 1 year.
However, there was a positive signal: In a subgroup analysis confined to the patients with inflammatory joints, the use of etanercept was associated with less structural damage of those joints over time as assessed using the quantitative Ghent University Scoring System, or GUSS, according to Dr. Kloppenburg, professor of rheumatology at Leiden (the Netherlands) University.
The emphatically negative results of the HUMOR trial were greeted with dismay by several disappointed audience members. They raised questions: Might a study featuring more than 12 weeks of treatment have brought positive results? How about a larger study? Why no placebo effect, given that patients were receiving injections? Is this area of investigation of TNF-inhibitor therapy now a dead end? Or could adalimumab and etanercept have differential efficacy in hand OA, even though they are both TNF inhibitors?
Dr. Aitken had an answer for every question.
“I think our study was big enough based on our power calculations to detect a difference of 15 mm on a visual analog scale, which is a clinically important difference. And that’s what we should be chasing in OA, that big effect. Patients are not going to be interested in a treatment that improves their pain by 5 mm,” she said.
As for the possibility that 12 weeks of adalimumab might have been too short to see a treatment effect, Dr. Aitken noted that anti-TNF therapy in rheumatoid arthritis brings a rapid response.
“Ideally, if you did have a disease-modifying drug for osteoarthritis you would want it to have a relatively quick response for pain; if patients aren’t seeing an effect after 3 months they might be less interested in taking it,” she continued.
Also, studies with a crossover design, like HUMOR, are known to have a much smaller placebo effect because patients know that at some point they’re certain to receive the active agent, Dr. Aitken observed.
As for the possibility that etanercept might be effective for erosive hand OA, while adalimumab is not, one physician commented, “That’s really scraping the bottom of the barrel.”
The HUMOR trial was sponsored by AbbVie. Dr. Aitken reported having no financial conflicts.
FROM OARSI 2017
Key clinical point:
Major finding: Scores dropped by an average of 3.0 points from a mean baseline of 63.6 with adalimumab and by 0.7 points with placebo on the primary endpoint of change in the visual analog pain score over the course of 12 weeks.
Data source: The HUMOR trial was a double-blind, placebo-controlled, randomized, crossover trial in which 43 participants with erosive hand osteoarthritis received 12 weeks of treatment with adalimumab and 12 weeks of placebo.
Disclosures: The study was sponsored by AbbVie. The presenter reported having no financial conflicts.