Osteoarthritis

 

LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.

Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.

“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.

Sara Freeman/MDedge News

Mr. Tiulpin, who is a doctoral student in the university’s research unit of medical imaging and technology, noted that, because of those problems, he and his fellow researchers sought out alternatives that would have higher sensitivity for early changes while also being cost-effective and widely available.

The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.

“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”

To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.

 

The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.

For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.

Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.

A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.

 

“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.

These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.

“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.

Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”

 

Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”

Mr. Tiulpin did not have any conflicts of interest to disclose.

SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.

 

LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.

Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.

“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.

Sara Freeman/MDedge News

Mr. Tiulpin, who is a doctoral student in the university’s research unit of medical imaging and technology, noted that, because of those problems, he and his fellow researchers sought out alternatives that would have higher sensitivity for early changes while also being cost-effective and widely available.

The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.

“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”

To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.

 

The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.

For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.

Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.

A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.

 

“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.

These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.

“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.

Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”

 

Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”

Mr. Tiulpin did not have any conflicts of interest to disclose.

SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.

 

LIVERPOOL, ENGLAND – The measurement of acoustic emissions and kinetic instability of the knee could become a promising noninvasive way to detect osteoarthritis (OA), according to a recent study.

Researchers at the University of Oulu (Finland) have developed a prototype device that allows multimodal assessment of the sound and motion of the knee.

“The OA diagnostic chain has many problems, some modalities are very expensive, and some have a low sensitivity as well,” said study investigator Aleksei Tiulpin, MSc, at the World Congress on Osteoarthritis, referring to magnetic resonance imaging, x-ray imaging, and symptomatic assessment, respectively.

Sara Freeman/MDedge News

Mr. Tiulpin, who is a doctoral student in the university’s research unit of medical imaging and technology, noted that, because of those problems, he and his fellow researchers sought out alternatives that would have higher sensitivity for early changes while also being cost-effective and widely available.

The investigational device that the research team has developed is worn like a brace around the knee and has microphones embedded within it to capture sound coming from the right and left sides of the knee. The device also uses two accelerometers, one placed on the thigh and one on the lower limb to measure movement simultaneously.

“We developed all the software and all the hardware ourselves for this project,” Mr. Tiulpin noted at the congress, sponsored by the Osteoarthritis Research Society International. “The acoustic and kinematic information was measured simultaneously.”

To see whether the prototype device was able to aid the diagnosis of OA, Mr. Tiulpin and his associates recruited 66 women aged 44-67 years old, roughly half of whom (51.5%) had radiographically confirmed knee OA of Kellgren-Lawrence grade 2 or higher.

 

The participants were asked to perform three exercise tests while wearing the device. First, they had to stand from a sitting position 10 times. Second, they were asked to extend the leg from the knee while sitting down (flexion-extension) 10 times. Third, and finally, they were asked to perform a one leg stand on the right leg twice.

For the acoustic data analysis, data from the standing phase of the sit-to-stand test and the extension phase of the flexion-extension tests were used. Mr. Tuilpin explained that the acoustic signals underwent processing to segment and filter them into candidate locations. The average sound patterns seen in the candidate locations were then analyzed, then a consistency analysis was undertaken. With this approach, inconsistent patterns of knee crepitation could be captured, Mr. Tiulpin explained.

Kinematic signals received from the movement sensors were used to determine the degree of knee instability. Higher signal magnitudes could potentially indicate stability problems, which can be quantified using signal power, Mr. Tiulpin’s slides stated.

A variety of statistical calculations were made to see how well the device might predict OA changes, and a model combining body mass index and age had an area under the curve of 84%, which suggested that it might be possible to improve OA detection with the addition of the device versus BMI and age alone.

 

“Our results indicated highly promising applications of the method,” Mr. Tiulpin suggested.

These findings are “very interesting,” commented one of the moderators of the session, Erwin van Spil, MD, of University Medical Center Utrecht (The Netherlands) as he opened up the floor to questions.

“I’ve had this question for years … what causes the clicks?” one delegate asked Mr. Tiulpin during discussion. He responded that it could be down to many things, one of which is cartilage components grinding against each other.

Dr. Spil, who was not involved in the study, commented in an interview that using acoustics in the detection of knee OA was still quite a novel concept. “It’s noninvasive, which is quite unique in our general approach, and it might enable an early diagnosis of OA, which is what we are aiming for.”

 

Although the study did have control subjects, it’s not clear at this point whether very early OA was being assessed, Dr. Spil suggested. “We did not have the opportunity to ask about the OA characteristics. I think they had radiographic OA, but we don’t know the grade and we were not informed about the clinical situation, so we don’t know if anyone had pain, for example.”

Mr. Tiulpin did not have any conflicts of interest to disclose.

SOURCE: Tiulpin A et al. Osteoarthritis Cartilage 2018;26(1):S40–S41.

LIVERPOOL, ENGLAND – A novel radiologic scoring system differentiated psoriatic arthritis (PsA) from nodal osteoarthritis (OA) of the hand in a pilot study.

“It’s a dilemma that’s faced, perhaps every couple of weeks, by most [rheumatologists]: Is it osteoarthritis or is it early psoriatic arthritis?” said Sardar Bahadur, MD, at the British Society for Rheumatology annual conference.

Sara Freeman/MDedge News

Both conditions are seen in daily practice, although the prevalence of hand OA is less frequent than knee OA. Approximately one in five of all adults in the United Kingdom have OA and 1%-2% have psoriasis. Of these, the prevalence of hand OA is about 11% and 0.1%-0.3% have psoriatic arthritis.

Being able to differentiate between the two conditions has important consequences for treatment, Dr. Bahadur said.

“Getting the diagnosis wrong could have major implications,” he said. “If you miss psoriatic arthritis, then potentially you are going to find irreversible joint damage causing pain and disability, and the opposite is also true, with misdiagnosis of osteoarthritis, with overuse of immunosuppression and all the cost implications as well as medicolegal consequences.”

Dr. Bahadur of the department of rehabilitation medicine and rheumatology at the Defence Medical Rehabilitation Centre Headley Court, in Epsom, England, added: “So early diagnosis is very important, it means early treatment, it means better care, potentially preventing serious and irreversible damage.”

Together with researchers at Guy’s and St Thomas’ NHS Trust, London, Dr. Bahadur hypothesized that changes in hand x-rays were distinct and could be reliably used to differentiate between the two conditions. They developed a scoring system for hand radiographs that looked at the differences in the interphalangeal joints, soft tissue, and bone features of patients with known OA or PsA.

 

Dr. Bahadur noted that the aim was to focus on plain film radiographs of the hands because these were inexpensive, universally accessible, did not rely on radiologists’ interpretation, and changes in the hands were known to occur in both OA and PsA.

A total of 99 sets of hand x-rays taken between 2008 and 2016 from 50 patients with OA and 49 patients with PsA were obtained. These were anonymized and then analyzed by a musculoskeletal radiologist using the scoring system the team had developed. The radiologist was unaware of the patients’ clinical status. The results were then compared to the clinical diagnosis.

The novel method of scoring each x-ray was then taught to two rheumatology and one radiology trainee during a 1-hour training session and were then asked to score the same radiographs.

 

Dr. Bahadur reported that the radiologist reported normal hand radiographs in five patients and, of the remaining 94 sets of left- and right-hand radiographs, the scoring system correctly allocated 100% of images to either PsA, OA, or rheumatoid arthritis (RA).

Of note was that the radiologist correctly identified two patients with nodal hand OA who later developed PsA several years later, and one patient with RA who was initially thought to have PsA.

“The system could be successfully used by nonradiologists,” Dr. Bahadur proposed. There was good agreement between the scoring system results and the clinical diagnosis then used by the trainees, with 88% and 67% of the radiographs correctly matched to the clinical diagnosis by the rheumatology trainees, and 70% for the radiology trainee.

Dr. Bahadur noted that the features that were consistently identified as being different between hand OA and PsA patients were soft tissue changes, such as dactylitis, as well as erosions, new bone formation, and other features such as subchondral surface changes and cysts.

 

The results of this single-center study show that the novel radiologic scoring system of hand radiographs was effective at differentiating patients with PsA from nodal OA.

“The ambition is to make this usable by nonradiologists,” Dr. Bahadur said. A multicenter trial would be the next step to look at the use of the scoring system.

Dr. Bahadur had no conflicts of interest to disclose.

SOURCE: Bahadur S et al. Rheumatology. 2018;57[Suppl. 3]:key075.184

LIVERPOOL, ENGLAND – A novel radiologic scoring system differentiated psoriatic arthritis (PsA) from nodal osteoarthritis (OA) of the hand in a pilot study.

“It’s a dilemma that’s faced, perhaps every couple of weeks, by most [rheumatologists]: Is it osteoarthritis or is it early psoriatic arthritis?” said Sardar Bahadur, MD, at the British Society for Rheumatology annual conference.

Sara Freeman/MDedge News

Both conditions are seen in daily practice, although the prevalence of hand OA is less frequent than knee OA. Approximately one in five of all adults in the United Kingdom have OA and 1%-2% have psoriasis. Of these, the prevalence of hand OA is about 11% and 0.1%-0.3% have psoriatic arthritis.

Being able to differentiate between the two conditions has important consequences for treatment, Dr. Bahadur said.

“Getting the diagnosis wrong could have major implications,” he said. “If you miss psoriatic arthritis, then potentially you are going to find irreversible joint damage causing pain and disability, and the opposite is also true, with misdiagnosis of osteoarthritis, with overuse of immunosuppression and all the cost implications as well as medicolegal consequences.”

Dr. Bahadur of the department of rehabilitation medicine and rheumatology at the Defence Medical Rehabilitation Centre Headley Court, in Epsom, England, added: “So early diagnosis is very important, it means early treatment, it means better care, potentially preventing serious and irreversible damage.”

Together with researchers at Guy’s and St Thomas’ NHS Trust, London, Dr. Bahadur hypothesized that changes in hand x-rays were distinct and could be reliably used to differentiate between the two conditions. They developed a scoring system for hand radiographs that looked at the differences in the interphalangeal joints, soft tissue, and bone features of patients with known OA or PsA.

 

Dr. Bahadur noted that the aim was to focus on plain film radiographs of the hands because these were inexpensive, universally accessible, did not rely on radiologists’ interpretation, and changes in the hands were known to occur in both OA and PsA.

A total of 99 sets of hand x-rays taken between 2008 and 2016 from 50 patients with OA and 49 patients with PsA were obtained. These were anonymized and then analyzed by a musculoskeletal radiologist using the scoring system the team had developed. The radiologist was unaware of the patients’ clinical status. The results were then compared to the clinical diagnosis.

The novel method of scoring each x-ray was then taught to two rheumatology and one radiology trainee during a 1-hour training session and were then asked to score the same radiographs.

 

Dr. Bahadur reported that the radiologist reported normal hand radiographs in five patients and, of the remaining 94 sets of left- and right-hand radiographs, the scoring system correctly allocated 100% of images to either PsA, OA, or rheumatoid arthritis (RA).

Of note was that the radiologist correctly identified two patients with nodal hand OA who later developed PsA several years later, and one patient with RA who was initially thought to have PsA.

“The system could be successfully used by nonradiologists,” Dr. Bahadur proposed. There was good agreement between the scoring system results and the clinical diagnosis then used by the trainees, with 88% and 67% of the radiographs correctly matched to the clinical diagnosis by the rheumatology trainees, and 70% for the radiology trainee.

Dr. Bahadur noted that the features that were consistently identified as being different between hand OA and PsA patients were soft tissue changes, such as dactylitis, as well as erosions, new bone formation, and other features such as subchondral surface changes and cysts.

 

The results of this single-center study show that the novel radiologic scoring system of hand radiographs was effective at differentiating patients with PsA from nodal OA.

“The ambition is to make this usable by nonradiologists,” Dr. Bahadur said. A multicenter trial would be the next step to look at the use of the scoring system.

Dr. Bahadur had no conflicts of interest to disclose.

SOURCE: Bahadur S et al. Rheumatology. 2018;57[Suppl. 3]:key075.184

LIVERPOOL, ENGLAND – A novel radiologic scoring system differentiated psoriatic arthritis (PsA) from nodal osteoarthritis (OA) of the hand in a pilot study.

“It’s a dilemma that’s faced, perhaps every couple of weeks, by most [rheumatologists]: Is it osteoarthritis or is it early psoriatic arthritis?” said Sardar Bahadur, MD, at the British Society for Rheumatology annual conference.

Sara Freeman/MDedge News

Both conditions are seen in daily practice, although the prevalence of hand OA is less frequent than knee OA. Approximately one in five of all adults in the United Kingdom have OA and 1%-2% have psoriasis. Of these, the prevalence of hand OA is about 11% and 0.1%-0.3% have psoriatic arthritis.

Being able to differentiate between the two conditions has important consequences for treatment, Dr. Bahadur said.

“Getting the diagnosis wrong could have major implications,” he said. “If you miss psoriatic arthritis, then potentially you are going to find irreversible joint damage causing pain and disability, and the opposite is also true, with misdiagnosis of osteoarthritis, with overuse of immunosuppression and all the cost implications as well as medicolegal consequences.”

Dr. Bahadur of the department of rehabilitation medicine and rheumatology at the Defence Medical Rehabilitation Centre Headley Court, in Epsom, England, added: “So early diagnosis is very important, it means early treatment, it means better care, potentially preventing serious and irreversible damage.”

Together with researchers at Guy’s and St Thomas’ NHS Trust, London, Dr. Bahadur hypothesized that changes in hand x-rays were distinct and could be reliably used to differentiate between the two conditions. They developed a scoring system for hand radiographs that looked at the differences in the interphalangeal joints, soft tissue, and bone features of patients with known OA or PsA.

 

Dr. Bahadur noted that the aim was to focus on plain film radiographs of the hands because these were inexpensive, universally accessible, did not rely on radiologists’ interpretation, and changes in the hands were known to occur in both OA and PsA.

A total of 99 sets of hand x-rays taken between 2008 and 2016 from 50 patients with OA and 49 patients with PsA were obtained. These were anonymized and then analyzed by a musculoskeletal radiologist using the scoring system the team had developed. The radiologist was unaware of the patients’ clinical status. The results were then compared to the clinical diagnosis.

The novel method of scoring each x-ray was then taught to two rheumatology and one radiology trainee during a 1-hour training session and were then asked to score the same radiographs.

 

Dr. Bahadur reported that the radiologist reported normal hand radiographs in five patients and, of the remaining 94 sets of left- and right-hand radiographs, the scoring system correctly allocated 100% of images to either PsA, OA, or rheumatoid arthritis (RA).

Of note was that the radiologist correctly identified two patients with nodal hand OA who later developed PsA several years later, and one patient with RA who was initially thought to have PsA.

“The system could be successfully used by nonradiologists,” Dr. Bahadur proposed. There was good agreement between the scoring system results and the clinical diagnosis then used by the trainees, with 88% and 67% of the radiographs correctly matched to the clinical diagnosis by the rheumatology trainees, and 70% for the radiology trainee.

Dr. Bahadur noted that the features that were consistently identified as being different between hand OA and PsA patients were soft tissue changes, such as dactylitis, as well as erosions, new bone formation, and other features such as subchondral surface changes and cysts.

 

The results of this single-center study show that the novel radiologic scoring system of hand radiographs was effective at differentiating patients with PsA from nodal OA.

“The ambition is to make this usable by nonradiologists,” Dr. Bahadur said. A multicenter trial would be the next step to look at the use of the scoring system.

Dr. Bahadur had no conflicts of interest to disclose.

SOURCE: Bahadur S et al. Rheumatology. 2018;57[Suppl. 3]:key075.184

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.

LIVERPOOL, ENGLAND – There was no significant reduction in pain from knee osteoarthritis (OA) with the use of investigational cannabidiol (CBD) gel ZYN002 in a phase 2a trial presented at the World Congress on Osteoarthritis.

The mean reductions in baseline knee pain scores from study entry to a 12-week assessment were –2.4 for placebo and –2.6 (P = .5) and –2.8 (P = .25), respectively, for a 250-mg and a 500-mg formulation of the gel.

Sara Freeman/MDedge

While there was a trend for benefit, it was “neither statistically or clinically significant,” reported David Hunter, MBBS, PhD.

However, he observed that a significantly (P = .016) greater number of patients who received the 250-mg dose (52.7%) were “composite responders,” compared with patients who received placebo (34.1%). A composite response was defined as at least a 30% reduction in pain, and a 20% decrease in WOMAC physical function subscale score at the last observation.

Although the percentage of composite responders was also higher than placebo with the 500-mg dose, the difference wasn’t significant (45.1% vs. 34.1%; P = .0169).

Post-hoc analyses also suggested that perhaps some patients may benefit more than others, reported Dr. Hunter, professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney.

For example, patients with baseline pain scores or 7 or more had greater mean reduction in pain at 12 weeks with both doses of the gel combined than placebo at week 4 (–2.2 vs. –1.6; P = .029), although the difference was not significant at week 8 (–3.0 vs. –2.2; P = .05) or 12 (–3.3 vs. –2.5; P = .086).

 

Women also exhibited a greater placebo response than did men, and “patients with less variability in baseline pain scores may have had greater separation between placebo and the treatment,” Dr. Hunter said. Indeed, 50%-52% of patients with less than 33% variation in baseline scores had a composite response to the gel, versus 27% for the placebo arm.

Evidence from preclinical models suggest that cannabinoids have antinociceptive and antihyperalgesic effects, Dr. Hunter explained at the congress, sponsored by the Osteoarthritis Research Society International. CBD has also been shown to have broad anti-inflammatory effects, and it may even promote osteoclast cell function and decrease bone resorption.

ZYN002 is a synthetic CBD formulated for transdermal delivery using a patented method to enhance its permeation through the skin. According to the manufacturer, Zynerba, it was developed for neuropsychiatric disorders, including fragile X syndrome, adult refractory epilepsy, and developmental and epileptic encephalopathies.

 

The primary aim of the phase 2 trial reported by Dr. Hunter was to assess ZYN002’s efficacy in managing osteoarthritis knee pain. Secondary objectives were to assess the gel’s safety and tolerability.

The STOP 1 (Synthetic Transdermal Cannabidiol for the Treatment of Knee Pain Due to Osteoarthritis) trial was a double-blind, placebo-controlled trial. For inclusion in the study, patients had to be between age 40 and 75 years and have had knee pain for at least 12 months because of primary OA, based on clinical and x-ray data as per American College of Rheumatology criteria. Anyone with a history of fibromyalgia or epilepsy was excluded.

A total of 320 patients with painful knee OA, with a mean age of 62 years, were randomized and underwent a 1-week washout period in which all their analgesic medications being used for osteoarthritis knee pain, except acetaminophen, were stopped. That was followed by a 7- to 10-day period when baseline daily worst pain levels were captured using a 0-10 numeric rating scale. Patients then underwent 12 weeks of treatment with either a high (500 mg) or a low (250 mg) dose of the gel, or placebo, given in twice-daily doses.

 

Just over a third (34%) of patients in the placebo arm discontinued the study, compared with 22% and 24% of those in the high- and low-dose gel arms. The main reason for discontinuation was withdrawn consent because of lack of efficacy in the placebo arm, with 8%, 8%, and 4% of patients, respectively, discontinuing because of adverse effects.

“Treatment-emergent adverse effects were roughly equally distributed across the three groups,” Dr. Hunter reported. The adverse events of more interest, he noted, were application site dryness, reaction, or pain. There was “a slight predisposition” to each of these in the 250-mg gel arm (5%, 3%, and 3% of patients affected) versus the 500-mg gel (3%, 0%, and 0%) and placebo (1%, 1%, 0%) arms.

SOURCE: Hunter D et al. Osteoarthritis Cartilage 2018:26(1):S26. Abstract 30.

 

LIVERPOOL, ENGLAND – Hip arthroscopic surgery produced better long-term results than did personalized hip physiotherapy for femoroacetabular impingement syndrome in a randomized trial conduced across multiple U.K. centers.

At 12 months, respective International Hip Outcome Tool-33 (iHOT-33) scores were 58.8 and 49.7, a difference of 9.1 points before and 6.8 points after adjustment for potential confounding factors (P = .0093).

Sara Freeman/MDedge News

“This difference was clinically important,” study investigator Nadine Foster, DPhil, said at the World Congress on Osteoarthritis. The iHOT-33 is a patient-reported outcome measure that rates quality of life on a 0-100 scale, with 0 indicating no impairment and 100 the worst impairment. A difference of 6.1 is considered clinically significant.

“This trial shows that hip arthroscopic surgery and personalized hip therapy both improved hip-related quality of life for patients with FAI [femoroacetabular impingement] syndrome, but that the surgery did indeed produce a greater improvement at our primary time point of 12 months,” she added. Dr. Foster is professor of musculoskeletal health in primary care at Keele University, Newcastle-under-Lyme, England, one of the 23 centers involved in the FASHIoN study in England, Wales, and Scotland.

“FAI is a very common cause of hip and groin pain in young adults, and it’s associated with the development of hip osteoarthritis,” Dr. Foster noted.

There are three types of FAI – pincer, cam, and combined. The pincer type of FAI is where there is “prominence or overcoverage of the rim of the acetabulum,” and the cam type is where there is a “bony prominence of the femoral head-neck junction,” she explained at the meeting sponsored by the Osteoarthritis Research Society International.

The link to OA comes when the femur and acetabulum prematurely connect, usually during activity, causing damage to the labrum and articular cartilage in the long term. Thus, treating FAI is important, not just for relieving patient’s pain and joint stiffness.

 

Hip arthroscopic surgery has become an established way of treating FAI syndrome – more than 2,400 operations were performed in 2013 in the United Kingdom alone, Dr. Foster observed. The aim of surgery is to try to reshape the hip joint to prevent impingement, and resect, repair, or reconstruct any intra-articular damage that may be present.

“Physiotherapy aims to improve hip muscle control and strength, and to correct the abnormal movement patterns that we see in these patients,” Dr. Foster said. “Through that, we hope to prevent the premature contact that occurs in FAI syndrome and thereby improve symptoms, allowing patients to return to activities and prevent recurrence.”

Working with physiotherapists, physicians, and surgeons, Dr. Foster and her associates have previously developed a “best conservative care” intervention that they call personalized hip therapy (PHT), which involves the delivery and supervision of an individualized exercise program by experienced physiotherapists over a 3- to 6-month period, and which patients repeat at home (PM R. 2013 May;5[5]:418-26).

The aim of the UK FASHIoN trial was to compare the clinical and cost-effectiveness of hip arthroscopy and PHT for FAI syndrome, as there was no robust clinical trial evidence to demonstrate a benefit of one over the other.

 

A total of 351 adults with hip and groin pain were randomized to either arthroscopic surgery (n = 173) or PHT (n = 178). The mean age of participants was 35 years, with no significant differences between the two treatment groups in terms of baseline demographics or type or duration of hip impingement.

While surgery was better in terms of patient outcomes, the study didn’t demonstrate its cost-effectiveness within the first 12 months, Dr. Foster observed. Cost-effectiveness, together with various other quality-of-life measurements, was a secondary endpoint of the study.

“Longer-term outcomes are required to establish whether improvement is sustained, and whether surgery is cost-effective at the longer time points for our health service,” she said.

Responding to a question about whether any of the patients in the study had radiographic evidence of osteoarthritis, Dr. Foster said that such patients had been excluded from the study.

 

“One of the hopes of the trial’s team is that, with the long-term follow-up, we might be able to get data at 5 and 10 years on things like hip osteoarthritis in these patients,” she said.

The study was funded by the National Institute for Health Research. Dr. Foster had no financial relationships or commercial interests to disclose.

SOURCE: Griffin DR et al. Osteoarthritis Cartilage. 2018:26(1):S24-25. Abstract 28

 

LIVERPOOL, ENGLAND – Hip arthroscopic surgery produced better long-term results than did personalized hip physiotherapy for femoroacetabular impingement syndrome in a randomized trial conduced across multiple U.K. centers.

At 12 months, respective International Hip Outcome Tool-33 (iHOT-33) scores were 58.8 and 49.7, a difference of 9.1 points before and 6.8 points after adjustment for potential confounding factors (P = .0093).

Sara Freeman/MDedge News

“This difference was clinically important,” study investigator Nadine Foster, DPhil, said at the World Congress on Osteoarthritis. The iHOT-33 is a patient-reported outcome measure that rates quality of life on a 0-100 scale, with 0 indicating no impairment and 100 the worst impairment. A difference of 6.1 is considered clinically significant.

“This trial shows that hip arthroscopic surgery and personalized hip therapy both improved hip-related quality of life for patients with FAI [femoroacetabular impingement] syndrome, but that the surgery did indeed produce a greater improvement at our primary time point of 12 months,” she added. Dr. Foster is professor of musculoskeletal health in primary care at Keele University, Newcastle-under-Lyme, England, one of the 23 centers involved in the FASHIoN study in England, Wales, and Scotland.

“FAI is a very common cause of hip and groin pain in young adults, and it’s associated with the development of hip osteoarthritis,” Dr. Foster noted.

There are three types of FAI – pincer, cam, and combined. The pincer type of FAI is where there is “prominence or overcoverage of the rim of the acetabulum,” and the cam type is where there is a “bony prominence of the femoral head-neck junction,” she explained at the meeting sponsored by the Osteoarthritis Research Society International.

The link to OA comes when the femur and acetabulum prematurely connect, usually during activity, causing damage to the labrum and articular cartilage in the long term. Thus, treating FAI is important, not just for relieving patient’s pain and joint stiffness.

 

Hip arthroscopic surgery has become an established way of treating FAI syndrome – more than 2,400 operations were performed in 2013 in the United Kingdom alone, Dr. Foster observed. The aim of surgery is to try to reshape the hip joint to prevent impingement, and resect, repair, or reconstruct any intra-articular damage that may be present.

“Physiotherapy aims to improve hip muscle control and strength, and to correct the abnormal movement patterns that we see in these patients,” Dr. Foster said. “Through that, we hope to prevent the premature contact that occurs in FAI syndrome and thereby improve symptoms, allowing patients to return to activities and prevent recurrence.”

Working with physiotherapists, physicians, and surgeons, Dr. Foster and her associates have previously developed a “best conservative care” intervention that they call personalized hip therapy (PHT), which involves the delivery and supervision of an individualized exercise program by experienced physiotherapists over a 3- to 6-month period, and which patients repeat at home (PM R. 2013 May;5[5]:418-26).

The aim of the UK FASHIoN trial was to compare the clinical and cost-effectiveness of hip arthroscopy and PHT for FAI syndrome, as there was no robust clinical trial evidence to demonstrate a benefit of one over the other.

 

A total of 351 adults with hip and groin pain were randomized to either arthroscopic surgery (n = 173) or PHT (n = 178). The mean age of participants was 35 years, with no significant differences between the two treatment groups in terms of baseline demographics or type or duration of hip impingement.

While surgery was better in terms of patient outcomes, the study didn’t demonstrate its cost-effectiveness within the first 12 months, Dr. Foster observed. Cost-effectiveness, together with various other quality-of-life measurements, was a secondary endpoint of the study.

“Longer-term outcomes are required to establish whether improvement is sustained, and whether surgery is cost-effective at the longer time points for our health service,” she said.

Responding to a question about whether any of the patients in the study had radiographic evidence of osteoarthritis, Dr. Foster said that such patients had been excluded from the study.

 

“One of the hopes of the trial’s team is that, with the long-term follow-up, we might be able to get data at 5 and 10 years on things like hip osteoarthritis in these patients,” she said.

The study was funded by the National Institute for Health Research. Dr. Foster had no financial relationships or commercial interests to disclose.

SOURCE: Griffin DR et al. Osteoarthritis Cartilage. 2018:26(1):S24-25. Abstract 28

 

LIVERPOOL, ENGLAND – Hip arthroscopic surgery produced better long-term results than did personalized hip physiotherapy for femoroacetabular impingement syndrome in a randomized trial conduced across multiple U.K. centers.

At 12 months, respective International Hip Outcome Tool-33 (iHOT-33) scores were 58.8 and 49.7, a difference of 9.1 points before and 6.8 points after adjustment for potential confounding factors (P = .0093).

Sara Freeman/MDedge News

“This difference was clinically important,” study investigator Nadine Foster, DPhil, said at the World Congress on Osteoarthritis. The iHOT-33 is a patient-reported outcome measure that rates quality of life on a 0-100 scale, with 0 indicating no impairment and 100 the worst impairment. A difference of 6.1 is considered clinically significant.

“This trial shows that hip arthroscopic surgery and personalized hip therapy both improved hip-related quality of life for patients with FAI [femoroacetabular impingement] syndrome, but that the surgery did indeed produce a greater improvement at our primary time point of 12 months,” she added. Dr. Foster is professor of musculoskeletal health in primary care at Keele University, Newcastle-under-Lyme, England, one of the 23 centers involved in the FASHIoN study in England, Wales, and Scotland.

“FAI is a very common cause of hip and groin pain in young adults, and it’s associated with the development of hip osteoarthritis,” Dr. Foster noted.

There are three types of FAI – pincer, cam, and combined. The pincer type of FAI is where there is “prominence or overcoverage of the rim of the acetabulum,” and the cam type is where there is a “bony prominence of the femoral head-neck junction,” she explained at the meeting sponsored by the Osteoarthritis Research Society International.

The link to OA comes when the femur and acetabulum prematurely connect, usually during activity, causing damage to the labrum and articular cartilage in the long term. Thus, treating FAI is important, not just for relieving patient’s pain and joint stiffness.

 

Hip arthroscopic surgery has become an established way of treating FAI syndrome – more than 2,400 operations were performed in 2013 in the United Kingdom alone, Dr. Foster observed. The aim of surgery is to try to reshape the hip joint to prevent impingement, and resect, repair, or reconstruct any intra-articular damage that may be present.

“Physiotherapy aims to improve hip muscle control and strength, and to correct the abnormal movement patterns that we see in these patients,” Dr. Foster said. “Through that, we hope to prevent the premature contact that occurs in FAI syndrome and thereby improve symptoms, allowing patients to return to activities and prevent recurrence.”

Working with physiotherapists, physicians, and surgeons, Dr. Foster and her associates have previously developed a “best conservative care” intervention that they call personalized hip therapy (PHT), which involves the delivery and supervision of an individualized exercise program by experienced physiotherapists over a 3- to 6-month period, and which patients repeat at home (PM R. 2013 May;5[5]:418-26).

The aim of the UK FASHIoN trial was to compare the clinical and cost-effectiveness of hip arthroscopy and PHT for FAI syndrome, as there was no robust clinical trial evidence to demonstrate a benefit of one over the other.

 

A total of 351 adults with hip and groin pain were randomized to either arthroscopic surgery (n = 173) or PHT (n = 178). The mean age of participants was 35 years, with no significant differences between the two treatment groups in terms of baseline demographics or type or duration of hip impingement.

While surgery was better in terms of patient outcomes, the study didn’t demonstrate its cost-effectiveness within the first 12 months, Dr. Foster observed. Cost-effectiveness, together with various other quality-of-life measurements, was a secondary endpoint of the study.

“Longer-term outcomes are required to establish whether improvement is sustained, and whether surgery is cost-effective at the longer time points for our health service,” she said.

Responding to a question about whether any of the patients in the study had radiographic evidence of osteoarthritis, Dr. Foster said that such patients had been excluded from the study.

 

“One of the hopes of the trial’s team is that, with the long-term follow-up, we might be able to get data at 5 and 10 years on things like hip osteoarthritis in these patients,” she said.

The study was funded by the National Institute for Health Research. Dr. Foster had no financial relationships or commercial interests to disclose.

SOURCE: Griffin DR et al. Osteoarthritis Cartilage. 2018:26(1):S24-25. Abstract 28

 

LIVERPOOL, ENGLAND – At 3 years of follow-up, the cartilage-building effects of sprifermin appear to be sustained, according to further data to be released from the phase 2 FORWARD trial.

The difference from placebo in mean cartilage thickness at the tibiofemoral joint (TFJ) at 3 years was 0.05 mm for a 100-mcg dose of sprifermin given every 6 months (P less than .0001), 0.02 mm for a 100-mcg dose given every 12 months (P = .193), 0.01 mm for a 50-mcg dose given every 6 months (P = .530), and –0.02 mm for a 50-mcg dose given every 12 months (P = .160).

“These data, 18 months after the last active injection, extend the results which we previously presented and assessed at 6 months after the last injection,” study investigator Marc Hochberg, MD, said at the World Congress on Osteoarthritis.

The prior 2-year findings, which were reported at the annual meeting of the American College of Rheumatology in November 2017, showed statistically significant dose-dependent structural modification in TFJ cartilage. Furthermore, the increase in cartilage thickness was seen in both medial and lateral compartments of the TFJ, and in the central medial subregion of the TFJ.

Sprifermin is one of several drugs currently being investigated as a potential disease-modifying osteoarthritis drug, none of which are currently licensed for use. It is a novel human recombinant version of fibroblast growth factor 18 that has been shown to increase chondrocyte proliferation that results in overall extracellular matrix production and subsequent hyaline-line cartilage formation.

The study comprised 549 patients with symptomatic radiographic primary femorotibial knee OA who were aged 40-85 years. For inclusion, patients had to have Kellgren-Lawrence Grade 2 or 3, with a medial minimum joint space width of 2.5 mm or more. In addition, patients had to have a history of OA pain for at least 6 months and either symptoms requiring pain medication or a pain score of 4-9 on the 10-point question 1 of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

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, noted that the current analysis at 3 years’ follow up had been prespecified and that the plan was to continue follow-up out to 5 years.

 

There was a statistically significant treatment effect and dose response effect seen in TFJ cartilage thickness.

“Although cartilage thickness declined in all treatment groups between years 2 and 3, the difference in cartilage thickness observed in year 2 with sprifermin at the highest dose [100 mcg every 6 months] versus placebo persisted through year 3,” Dr. Hochberg said at the congress, which was sponsored by the Osteoarthritis Research Society International.

Sara Freeman/MDedge News

As for secondary endpoints of thickness in the medial and lateral tibiofemoral cartilage, “there are significant differences between the higher-dose sprifermin group and the placebo group,” he said.

“Based on imaging, sprifermin appears to be effective at modifying structural changes in articular cartilage in a dose-dependent manner in patients with knee osteoarthritis, with an acceptable safety profile.”

 

Dr. Hochberg added that there was “marked symptomatic improvement” as shown by changes in WOMAC scores in all treatment groups including placebo. The improvement in total WOMAC scores by approximately 50% in all treatment groups by the second year was continued to the third year.

Adverse effects occurred with a similar frequency in the active treatment groups and the placebo group. They were also of a similar nature. The most commonly reported side effects involved the musculoskeletal system or were connective tissue disorders (e.g. arthralgia). Importantly, there was no difference in the frequency, severity, or nature of serious adverse events, treatment-related adverse events, or discontinuation due to adverse events with active versus placebo therapy, Dr. Hochberg said.

The percentages of patients completing the study to the second and third years were a respective 87.8% and 81.6% in the sprifermin groups and 80.6% and 75.9% in the placebo group.

Merck KGaA and EMD Serono Research Institute funded the study. Dr. Hochberg has received consulting fees from EMD Serono and multiple other companies developing treatments for OA.

SOURCE: Hochberg M et al. Osteoarthritis Cartilage. 2018:26(1):S26-27. Abstract 32

 

LIVERPOOL, ENGLAND – At 3 years of follow-up, the cartilage-building effects of sprifermin appear to be sustained, according to further data to be released from the phase 2 FORWARD trial.

The difference from placebo in mean cartilage thickness at the tibiofemoral joint (TFJ) at 3 years was 0.05 mm for a 100-mcg dose of sprifermin given every 6 months (P less than .0001), 0.02 mm for a 100-mcg dose given every 12 months (P = .193), 0.01 mm for a 50-mcg dose given every 6 months (P = .530), and –0.02 mm for a 50-mcg dose given every 12 months (P = .160).

“These data, 18 months after the last active injection, extend the results which we previously presented and assessed at 6 months after the last injection,” study investigator Marc Hochberg, MD, said at the World Congress on Osteoarthritis.

The prior 2-year findings, which were reported at the annual meeting of the American College of Rheumatology in November 2017, showed statistically significant dose-dependent structural modification in TFJ cartilage. Furthermore, the increase in cartilage thickness was seen in both medial and lateral compartments of the TFJ, and in the central medial subregion of the TFJ.

Sprifermin is one of several drugs currently being investigated as a potential disease-modifying osteoarthritis drug, none of which are currently licensed for use. It is a novel human recombinant version of fibroblast growth factor 18 that has been shown to increase chondrocyte proliferation that results in overall extracellular matrix production and subsequent hyaline-line cartilage formation.

The study comprised 549 patients with symptomatic radiographic primary femorotibial knee OA who were aged 40-85 years. For inclusion, patients had to have Kellgren-Lawrence Grade 2 or 3, with a medial minimum joint space width of 2.5 mm or more. In addition, patients had to have a history of OA pain for at least 6 months and either symptoms requiring pain medication or a pain score of 4-9 on the 10-point question 1 of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

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, noted that the current analysis at 3 years’ follow up had been prespecified and that the plan was to continue follow-up out to 5 years.

 

There was a statistically significant treatment effect and dose response effect seen in TFJ cartilage thickness.

“Although cartilage thickness declined in all treatment groups between years 2 and 3, the difference in cartilage thickness observed in year 2 with sprifermin at the highest dose [100 mcg every 6 months] versus placebo persisted through year 3,” Dr. Hochberg said at the congress, which was sponsored by the Osteoarthritis Research Society International.

Sara Freeman/MDedge News

As for secondary endpoints of thickness in the medial and lateral tibiofemoral cartilage, “there are significant differences between the higher-dose sprifermin group and the placebo group,” he said.

“Based on imaging, sprifermin appears to be effective at modifying structural changes in articular cartilage in a dose-dependent manner in patients with knee osteoarthritis, with an acceptable safety profile.”

 

Dr. Hochberg added that there was “marked symptomatic improvement” as shown by changes in WOMAC scores in all treatment groups including placebo. The improvement in total WOMAC scores by approximately 50% in all treatment groups by the second year was continued to the third year.

Adverse effects occurred with a similar frequency in the active treatment groups and the placebo group. They were also of a similar nature. The most commonly reported side effects involved the musculoskeletal system or were connective tissue disorders (e.g. arthralgia). Importantly, there was no difference in the frequency, severity, or nature of serious adverse events, treatment-related adverse events, or discontinuation due to adverse events with active versus placebo therapy, Dr. Hochberg said.

The percentages of patients completing the study to the second and third years were a respective 87.8% and 81.6% in the sprifermin groups and 80.6% and 75.9% in the placebo group.

Merck KGaA and EMD Serono Research Institute funded the study. Dr. Hochberg has received consulting fees from EMD Serono and multiple other companies developing treatments for OA.

SOURCE: Hochberg M et al. Osteoarthritis Cartilage. 2018:26(1):S26-27. Abstract 32

 

LIVERPOOL, ENGLAND – At 3 years of follow-up, the cartilage-building effects of sprifermin appear to be sustained, according to further data to be released from the phase 2 FORWARD trial.

The difference from placebo in mean cartilage thickness at the tibiofemoral joint (TFJ) at 3 years was 0.05 mm for a 100-mcg dose of sprifermin given every 6 months (P less than .0001), 0.02 mm for a 100-mcg dose given every 12 months (P = .193), 0.01 mm for a 50-mcg dose given every 6 months (P = .530), and –0.02 mm for a 50-mcg dose given every 12 months (P = .160).

“These data, 18 months after the last active injection, extend the results which we previously presented and assessed at 6 months after the last injection,” study investigator Marc Hochberg, MD, said at the World Congress on Osteoarthritis.

The prior 2-year findings, which were reported at the annual meeting of the American College of Rheumatology in November 2017, showed statistically significant dose-dependent structural modification in TFJ cartilage. Furthermore, the increase in cartilage thickness was seen in both medial and lateral compartments of the TFJ, and in the central medial subregion of the TFJ.

Sprifermin is one of several drugs currently being investigated as a potential disease-modifying osteoarthritis drug, none of which are currently licensed for use. It is a novel human recombinant version of fibroblast growth factor 18 that has been shown to increase chondrocyte proliferation that results in overall extracellular matrix production and subsequent hyaline-line cartilage formation.

The study comprised 549 patients with symptomatic radiographic primary femorotibial knee OA who were aged 40-85 years. For inclusion, patients had to have Kellgren-Lawrence Grade 2 or 3, with a medial minimum joint space width of 2.5 mm or more. In addition, patients had to have a history of OA pain for at least 6 months and either symptoms requiring pain medication or a pain score of 4-9 on the 10-point question 1 of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

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, noted that the current analysis at 3 years’ follow up had been prespecified and that the plan was to continue follow-up out to 5 years.

 

There was a statistically significant treatment effect and dose response effect seen in TFJ cartilage thickness.

“Although cartilage thickness declined in all treatment groups between years 2 and 3, the difference in cartilage thickness observed in year 2 with sprifermin at the highest dose [100 mcg every 6 months] versus placebo persisted through year 3,” Dr. Hochberg said at the congress, which was sponsored by the Osteoarthritis Research Society International.

Sara Freeman/MDedge News

As for secondary endpoints of thickness in the medial and lateral tibiofemoral cartilage, “there are significant differences between the higher-dose sprifermin group and the placebo group,” he said.

“Based on imaging, sprifermin appears to be effective at modifying structural changes in articular cartilage in a dose-dependent manner in patients with knee osteoarthritis, with an acceptable safety profile.”

 

Dr. Hochberg added that there was “marked symptomatic improvement” as shown by changes in WOMAC scores in all treatment groups including placebo. The improvement in total WOMAC scores by approximately 50% in all treatment groups by the second year was continued to the third year.

Adverse effects occurred with a similar frequency in the active treatment groups and the placebo group. They were also of a similar nature. The most commonly reported side effects involved the musculoskeletal system or were connective tissue disorders (e.g. arthralgia). Importantly, there was no difference in the frequency, severity, or nature of serious adverse events, treatment-related adverse events, or discontinuation due to adverse events with active versus placebo therapy, Dr. Hochberg said.

The percentages of patients completing the study to the second and third years were a respective 87.8% and 81.6% in the sprifermin groups and 80.6% and 75.9% in the placebo group.

Merck KGaA and EMD Serono Research Institute funded the study. Dr. Hochberg has received consulting fees from EMD Serono and multiple other companies developing treatments for OA.

SOURCE: Hochberg M et al. Osteoarthritis Cartilage. 2018:26(1):S26-27. Abstract 32

 

LIVERPOOL, ENGLAND – With many active phase 3 trials of promising agents, the “future looks bright for growth factors and disease modification” in osteoarthritis (OA), according to David Hunter, MBBS, PhD.

Dr. Hunter, who is the Florance and Cope Chair of Rheumatology and professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney, Australia, outlined some of the recent research with these agents in OA.

Sara Freeman/MDedge News

There has been declining mortality from all causes over the years, thanks to improvements in cardiovascular and other fields of medicine, with subsequent increasing life expectancy, Dr. Hunter pointed out. This is important if you consider that OA remains one of the most prevailing forms of joint disease, and data suggest people are developing OA at younger ages than in the past.

In 2013, a U.S. study (Arthritis Care Res. 2013;65[5]:703-11) showed that the 2007-2008 incidence of symptomatic knee OA was highest between the ages of 54 and 64 years, with the estimated median age at diagnosis of 55.8 years. Patients were substantially younger than were those who had been diagnosed at a median age of 68.5 years more than a decade earlier in 1991-1992.

“So, we’re developing [OA] at a much earlier age, but we’re obviously living longer and living with that morbidity for a substantial period of time,” Dr. Hunter said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

“It’s within that context that we really need to think about both the individual and societal burden of osteoarthritis, and why we’re developing agents such as growth factors to help retard symptoms related to disease,” continued Dr. Hunter, chair of the Institute of Bone and Joint Research, deputy dean of the Northern Clinical School, and consultant rheumatologist at North Sydney Orthopaedic and Sports Medicine Centre, Sydney.

OA is characterized by articular cartilage damage, low-grade synovial inflammation, and hypertrophic bone changes that lead to pain and functional deterioration (Expert Opin Emerg Drugs. 2015;20[3]:361-78). Attempts to modify the disease process have thus focused on these three areas, aiming to regulate cartilage catabolism and anabolism, control inflammation, and remodel subchondral bone (Rheumatology [Oxford]. 2018;57[suppl. 4]:iv108-iv123).

 

Growth factors fall under the category of regulating cartilage catabolism and anabolism, playing a “significant role in musculoskeletal tissues’ homeostasis and repair,” Dr. Hunter explained. “They influence chemotaxis, differentiation, proliferation, and synthetic activity of cartilage and bone cells, and can regulate physiological remodeling and cartilage healing.”

Examples of growth factors of interest in OA include transforming growth factor-beta superfamily and bone morphogenic proteins 2 and 7, fibroblast growth factors 2 and 18, and insulin-like growth factor-1.

Two currently unproven and somewhat controversial ways of regulating cartilage catabolism and anabolism is the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). Neither are ready for widespread use, Dr. Hunter observed, and more data on these approaches still need to be gathered.

The rationale behind the use of MSCs is that all joint tissues contain these cells, and they can potentially differentiate into cartilage, bone, or other tissues. There are changes in the quantity, phenotype, and differentiation potential of these cells in patients with OA, however, leading researchers to see if intra-articular injection of MSCs could be a possible therapeutic strategy. MSCs can be isolated from a number of different tissues and differentiate into multiple cells types. Animal model data suggest that their transplantation into an affected joint can stimulate articular repair.

 

“From a clinical perspective, there have been a vast array of clinical trials looking at different types of MSCs and different types of administration,” Dr. Hunter noted. Pooled data suggest that stem cell therapy does help to improve pain and function. However, the quality of trials has been called into question, with a positive publication bias suggested. There’s no clear evidence of any structural benefits, Dr. Hunter stated. “There’s a lot of stem cells being used for clinical purposes without the evidence to support their efficacy,” he cautioned. “We need much better regulation.”

There are several PRP agents, which deliver growth factors, cytokines, adhesive proteins, and other plasma proteins, such as clotting factors. It’s unknown how PRP therapy works in OA, whether it is just pain relieving or could affect the progression of joint damage. So far, studies have been done only in knee OA, so data in other joints need to be obtained.

“Whilst they have great potential, the literature on the use of PRP is conflicting,” Dr. Hunter said. “There are a lot of positive trials out there, but their quality in general is quite low.”

Better data are perhaps available for the recombinant human fibroblast growth factor–18 sprifermin, with recent 3-year data from an ongoing 5-year randomized, placebo-controlled, phase 2 study showing increased total cartilage thickness in the tibiofemoral joint relative to placebo. “There does appear to be a structure benefit,” Dr. Hunter said of sprifermin’s effects in the study versus intra-articular saline.

 

Although improvement in total Western Ontario and McMaster Universities Osteoarthritis Index scores were seen in the patients with knee OA, there was no real differentiation by dose or by placebo. The rationale for having a longer trial follow-up – the last dose of sprifermin was given at 18 months – is to see if there is a later effect.

In the later stages of development is Invossa TissueGene-C; this is drug that consists of patients’ normal and genetically-modified chondrocyte cells that express transforming growth factor-beta 1. Phase 2 findings have shown that it can improve pain and function scores in patients with moderate to advanced knee OA (BMC Musculoskelet Disord. 2017;18[1]:461). Based on those findings, two phase 3 trials are currently underway, with some further findings presented elsewhere at the OARSI meeting.

Even though there is still no disease-modifying osteoarthritis drug currently licensed for use, “I’m really positive about all of what we’ve learned, particularly with the application to future trials and ongoing trials in this space,” Dr. Hunter observed.

“Future strategies should differentiate between those agents aiming to reduce pain, and those targeting structural evolution, incorporating a combination of anabolic and anti-catabolic therapies,” Dr. Hunter suggested. One of the challenges, however, is to address the placebo effect, which can be exaggerated by the context of administration or surgery.

 

Furthermore, he proposed that new treatments should “fit into the natural progression of OA” by focusing on early disease where changes might still be reversible. “We’re getting more nuanced about where to intervene,” Dr. Hunter said.

Emerging treatments should also take the location of the disease and its heterogenic nature into account.

Dr. Hunter has consulted for Zynerba, TLC, Kolon TissueGene, and Merck Serono, and he disclosed receiving royalties from DJO for a patellofemoral brace patent.

SOURCE: Lohmander S et al. Osteoarthritis Cartilage. 2018:26(1):S6. Abstract I-18

 

LIVERPOOL, ENGLAND – With many active phase 3 trials of promising agents, the “future looks bright for growth factors and disease modification” in osteoarthritis (OA), according to David Hunter, MBBS, PhD.

Dr. Hunter, who is the Florance and Cope Chair of Rheumatology and professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney, Australia, outlined some of the recent research with these agents in OA.

Sara Freeman/MDedge News

There has been declining mortality from all causes over the years, thanks to improvements in cardiovascular and other fields of medicine, with subsequent increasing life expectancy, Dr. Hunter pointed out. This is important if you consider that OA remains one of the most prevailing forms of joint disease, and data suggest people are developing OA at younger ages than in the past.

In 2013, a U.S. study (Arthritis Care Res. 2013;65[5]:703-11) showed that the 2007-2008 incidence of symptomatic knee OA was highest between the ages of 54 and 64 years, with the estimated median age at diagnosis of 55.8 years. Patients were substantially younger than were those who had been diagnosed at a median age of 68.5 years more than a decade earlier in 1991-1992.

“So, we’re developing [OA] at a much earlier age, but we’re obviously living longer and living with that morbidity for a substantial period of time,” Dr. Hunter said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

“It’s within that context that we really need to think about both the individual and societal burden of osteoarthritis, and why we’re developing agents such as growth factors to help retard symptoms related to disease,” continued Dr. Hunter, chair of the Institute of Bone and Joint Research, deputy dean of the Northern Clinical School, and consultant rheumatologist at North Sydney Orthopaedic and Sports Medicine Centre, Sydney.

OA is characterized by articular cartilage damage, low-grade synovial inflammation, and hypertrophic bone changes that lead to pain and functional deterioration (Expert Opin Emerg Drugs. 2015;20[3]:361-78). Attempts to modify the disease process have thus focused on these three areas, aiming to regulate cartilage catabolism and anabolism, control inflammation, and remodel subchondral bone (Rheumatology [Oxford]. 2018;57[suppl. 4]:iv108-iv123).

 

Growth factors fall under the category of regulating cartilage catabolism and anabolism, playing a “significant role in musculoskeletal tissues’ homeostasis and repair,” Dr. Hunter explained. “They influence chemotaxis, differentiation, proliferation, and synthetic activity of cartilage and bone cells, and can regulate physiological remodeling and cartilage healing.”

Examples of growth factors of interest in OA include transforming growth factor-beta superfamily and bone morphogenic proteins 2 and 7, fibroblast growth factors 2 and 18, and insulin-like growth factor-1.

Two currently unproven and somewhat controversial ways of regulating cartilage catabolism and anabolism is the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). Neither are ready for widespread use, Dr. Hunter observed, and more data on these approaches still need to be gathered.

The rationale behind the use of MSCs is that all joint tissues contain these cells, and they can potentially differentiate into cartilage, bone, or other tissues. There are changes in the quantity, phenotype, and differentiation potential of these cells in patients with OA, however, leading researchers to see if intra-articular injection of MSCs could be a possible therapeutic strategy. MSCs can be isolated from a number of different tissues and differentiate into multiple cells types. Animal model data suggest that their transplantation into an affected joint can stimulate articular repair.

 

“From a clinical perspective, there have been a vast array of clinical trials looking at different types of MSCs and different types of administration,” Dr. Hunter noted. Pooled data suggest that stem cell therapy does help to improve pain and function. However, the quality of trials has been called into question, with a positive publication bias suggested. There’s no clear evidence of any structural benefits, Dr. Hunter stated. “There’s a lot of stem cells being used for clinical purposes without the evidence to support their efficacy,” he cautioned. “We need much better regulation.”

There are several PRP agents, which deliver growth factors, cytokines, adhesive proteins, and other plasma proteins, such as clotting factors. It’s unknown how PRP therapy works in OA, whether it is just pain relieving or could affect the progression of joint damage. So far, studies have been done only in knee OA, so data in other joints need to be obtained.

“Whilst they have great potential, the literature on the use of PRP is conflicting,” Dr. Hunter said. “There are a lot of positive trials out there, but their quality in general is quite low.”

Better data are perhaps available for the recombinant human fibroblast growth factor–18 sprifermin, with recent 3-year data from an ongoing 5-year randomized, placebo-controlled, phase 2 study showing increased total cartilage thickness in the tibiofemoral joint relative to placebo. “There does appear to be a structure benefit,” Dr. Hunter said of sprifermin’s effects in the study versus intra-articular saline.

 

Although improvement in total Western Ontario and McMaster Universities Osteoarthritis Index scores were seen in the patients with knee OA, there was no real differentiation by dose or by placebo. The rationale for having a longer trial follow-up – the last dose of sprifermin was given at 18 months – is to see if there is a later effect.

In the later stages of development is Invossa TissueGene-C; this is drug that consists of patients’ normal and genetically-modified chondrocyte cells that express transforming growth factor-beta 1. Phase 2 findings have shown that it can improve pain and function scores in patients with moderate to advanced knee OA (BMC Musculoskelet Disord. 2017;18[1]:461). Based on those findings, two phase 3 trials are currently underway, with some further findings presented elsewhere at the OARSI meeting.

Even though there is still no disease-modifying osteoarthritis drug currently licensed for use, “I’m really positive about all of what we’ve learned, particularly with the application to future trials and ongoing trials in this space,” Dr. Hunter observed.

“Future strategies should differentiate between those agents aiming to reduce pain, and those targeting structural evolution, incorporating a combination of anabolic and anti-catabolic therapies,” Dr. Hunter suggested. One of the challenges, however, is to address the placebo effect, which can be exaggerated by the context of administration or surgery.

 

Furthermore, he proposed that new treatments should “fit into the natural progression of OA” by focusing on early disease where changes might still be reversible. “We’re getting more nuanced about where to intervene,” Dr. Hunter said.

Emerging treatments should also take the location of the disease and its heterogenic nature into account.

Dr. Hunter has consulted for Zynerba, TLC, Kolon TissueGene, and Merck Serono, and he disclosed receiving royalties from DJO for a patellofemoral brace patent.

SOURCE: Lohmander S et al. Osteoarthritis Cartilage. 2018:26(1):S6. Abstract I-18

 

LIVERPOOL, ENGLAND – With many active phase 3 trials of promising agents, the “future looks bright for growth factors and disease modification” in osteoarthritis (OA), according to David Hunter, MBBS, PhD.

Dr. Hunter, who is the Florance and Cope Chair of Rheumatology and professor of medicine at the University of Sydney and the Royal North Shore Hospital, Sydney, Australia, outlined some of the recent research with these agents in OA.

Sara Freeman/MDedge News

There has been declining mortality from all causes over the years, thanks to improvements in cardiovascular and other fields of medicine, with subsequent increasing life expectancy, Dr. Hunter pointed out. This is important if you consider that OA remains one of the most prevailing forms of joint disease, and data suggest people are developing OA at younger ages than in the past.

In 2013, a U.S. study (Arthritis Care Res. 2013;65[5]:703-11) showed that the 2007-2008 incidence of symptomatic knee OA was highest between the ages of 54 and 64 years, with the estimated median age at diagnosis of 55.8 years. Patients were substantially younger than were those who had been diagnosed at a median age of 68.5 years more than a decade earlier in 1991-1992.

“So, we’re developing [OA] at a much earlier age, but we’re obviously living longer and living with that morbidity for a substantial period of time,” Dr. Hunter said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

“It’s within that context that we really need to think about both the individual and societal burden of osteoarthritis, and why we’re developing agents such as growth factors to help retard symptoms related to disease,” continued Dr. Hunter, chair of the Institute of Bone and Joint Research, deputy dean of the Northern Clinical School, and consultant rheumatologist at North Sydney Orthopaedic and Sports Medicine Centre, Sydney.

OA is characterized by articular cartilage damage, low-grade synovial inflammation, and hypertrophic bone changes that lead to pain and functional deterioration (Expert Opin Emerg Drugs. 2015;20[3]:361-78). Attempts to modify the disease process have thus focused on these three areas, aiming to regulate cartilage catabolism and anabolism, control inflammation, and remodel subchondral bone (Rheumatology [Oxford]. 2018;57[suppl. 4]:iv108-iv123).

 

Growth factors fall under the category of regulating cartilage catabolism and anabolism, playing a “significant role in musculoskeletal tissues’ homeostasis and repair,” Dr. Hunter explained. “They influence chemotaxis, differentiation, proliferation, and synthetic activity of cartilage and bone cells, and can regulate physiological remodeling and cartilage healing.”

Examples of growth factors of interest in OA include transforming growth factor-beta superfamily and bone morphogenic proteins 2 and 7, fibroblast growth factors 2 and 18, and insulin-like growth factor-1.

Two currently unproven and somewhat controversial ways of regulating cartilage catabolism and anabolism is the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). Neither are ready for widespread use, Dr. Hunter observed, and more data on these approaches still need to be gathered.

The rationale behind the use of MSCs is that all joint tissues contain these cells, and they can potentially differentiate into cartilage, bone, or other tissues. There are changes in the quantity, phenotype, and differentiation potential of these cells in patients with OA, however, leading researchers to see if intra-articular injection of MSCs could be a possible therapeutic strategy. MSCs can be isolated from a number of different tissues and differentiate into multiple cells types. Animal model data suggest that their transplantation into an affected joint can stimulate articular repair.

 

“From a clinical perspective, there have been a vast array of clinical trials looking at different types of MSCs and different types of administration,” Dr. Hunter noted. Pooled data suggest that stem cell therapy does help to improve pain and function. However, the quality of trials has been called into question, with a positive publication bias suggested. There’s no clear evidence of any structural benefits, Dr. Hunter stated. “There’s a lot of stem cells being used for clinical purposes without the evidence to support their efficacy,” he cautioned. “We need much better regulation.”

There are several PRP agents, which deliver growth factors, cytokines, adhesive proteins, and other plasma proteins, such as clotting factors. It’s unknown how PRP therapy works in OA, whether it is just pain relieving or could affect the progression of joint damage. So far, studies have been done only in knee OA, so data in other joints need to be obtained.

“Whilst they have great potential, the literature on the use of PRP is conflicting,” Dr. Hunter said. “There are a lot of positive trials out there, but their quality in general is quite low.”

Better data are perhaps available for the recombinant human fibroblast growth factor–18 sprifermin, with recent 3-year data from an ongoing 5-year randomized, placebo-controlled, phase 2 study showing increased total cartilage thickness in the tibiofemoral joint relative to placebo. “There does appear to be a structure benefit,” Dr. Hunter said of sprifermin’s effects in the study versus intra-articular saline.

 

Although improvement in total Western Ontario and McMaster Universities Osteoarthritis Index scores were seen in the patients with knee OA, there was no real differentiation by dose or by placebo. The rationale for having a longer trial follow-up – the last dose of sprifermin was given at 18 months – is to see if there is a later effect.

In the later stages of development is Invossa TissueGene-C; this is drug that consists of patients’ normal and genetically-modified chondrocyte cells that express transforming growth factor-beta 1. Phase 2 findings have shown that it can improve pain and function scores in patients with moderate to advanced knee OA (BMC Musculoskelet Disord. 2017;18[1]:461). Based on those findings, two phase 3 trials are currently underway, with some further findings presented elsewhere at the OARSI meeting.

Even though there is still no disease-modifying osteoarthritis drug currently licensed for use, “I’m really positive about all of what we’ve learned, particularly with the application to future trials and ongoing trials in this space,” Dr. Hunter observed.

“Future strategies should differentiate between those agents aiming to reduce pain, and those targeting structural evolution, incorporating a combination of anabolic and anti-catabolic therapies,” Dr. Hunter suggested. One of the challenges, however, is to address the placebo effect, which can be exaggerated by the context of administration or surgery.

 

Furthermore, he proposed that new treatments should “fit into the natural progression of OA” by focusing on early disease where changes might still be reversible. “We’re getting more nuanced about where to intervene,” Dr. Hunter said.

Emerging treatments should also take the location of the disease and its heterogenic nature into account.

Dr. Hunter has consulted for Zynerba, TLC, Kolon TissueGene, and Merck Serono, and he disclosed receiving royalties from DJO for a patellofemoral brace patent.

SOURCE: Lohmander S et al. Osteoarthritis Cartilage. 2018:26(1):S6. Abstract I-18

 

LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.

Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.

Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).

There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).

Sara Freeman/MDedge News

Furthermore, evaluation of MRI scans, x-rays, and liquid biomarkers showed “all directed towards slowing disease progression,” Bumsup Lee, PhD, and his associates reported at the World Congress on Osteoarthritis.

“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta₁. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.

Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.

 

At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.

Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).

The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.

A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm² or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.

 

At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.

Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.

X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).

TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.

 

The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.

“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States

The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.

SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.

 

LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.

Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.

Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).

There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).

Sara Freeman/MDedge News

Furthermore, evaluation of MRI scans, x-rays, and liquid biomarkers showed “all directed towards slowing disease progression,” Bumsup Lee, PhD, and his associates reported at the World Congress on Osteoarthritis.

“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta₁. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.

Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.

 

At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.

Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).

The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.

A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm² or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.

 

At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.

Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.

X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).

TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.

 

The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.

“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States

The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.

SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.

 

LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.

Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.

Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).

There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).

Sara Freeman/MDedge News

Furthermore, evaluation of MRI scans, x-rays, and liquid biomarkers showed “all directed towards slowing disease progression,” Bumsup Lee, PhD, and his associates reported at the World Congress on Osteoarthritis.

“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta₁. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.

Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.

 

At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.

Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).

The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.

A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm² or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.

 

At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.

Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.

X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).

TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.

 

The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.

“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States

The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.

SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.

 

LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.

An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).

The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.

“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.

There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.

“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.

Sara Freeman/MDedge News

For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.

 

All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.

Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m² who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.

Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.

At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.

 

Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.

There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).

“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.

“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.

 

The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.

The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.

SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.

 

LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.

An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).

The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.

“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.

There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.

“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.

Sara Freeman/MDedge News

For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.

 

All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.

Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m² who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.

Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.

At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.

 

Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.

There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).

“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.

“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.

 

The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.

The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.

SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.

 

LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.

An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).

The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.

“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.

There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.

“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.

Sara Freeman/MDedge News

For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.

 

All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.

Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m² who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.

Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.

At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.

 

Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.

There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).

“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.

“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.

 

The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.

The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.

SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.

 

LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.

The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.

Sara Freeman/MDedge News

Indeed, relative to placebo, 63%-66% reductions in the medial femur bone area progression were observed with MIV-711. The loss of medial femur cartilage thickness was around 65 mm for placebo, but 10.5-22.0 mm in patients who received treatment.

MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.

The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.

While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.

“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.

 

“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.

Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.

MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.

The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.

 

Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.

In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m², and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.

“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).

“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.

 

“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.

“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.

The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.

SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
 

 

LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.

The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.

Sara Freeman/MDedge News

Indeed, relative to placebo, 63%-66% reductions in the medial femur bone area progression were observed with MIV-711. The loss of medial femur cartilage thickness was around 65 mm for placebo, but 10.5-22.0 mm in patients who received treatment.

MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.

The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.

While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.

“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.

 

“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.

Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.

MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.

The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.

 

Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.

In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m², and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.

“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).

“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.

 

“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.

“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.

The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.

SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
 

 

LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.

The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.

Sara Freeman/MDedge News

Indeed, relative to placebo, 63%-66% reductions in the medial femur bone area progression were observed with MIV-711. The loss of medial femur cartilage thickness was around 65 mm for placebo, but 10.5-22.0 mm in patients who received treatment.

MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.

The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.

While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.

“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.

 

“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.

Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.

MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.

The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.

 

Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.

In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m², and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.

“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).

“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.

 

“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.

“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.

The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.

SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
 

 

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

Furthermore, of 136 patients who underwent X-rays that were graded by an experienced radiologist, 6% had knee replacements and about 70% had developed knee OA.

The link between OA and ACL injury is not new, with prior estimates suggesting that up to half of all patients with ACL injury develop OA within 10 years of the injury, said Stephanie Filbay, PhD, who presented the results of the study at the World Congress on Osteoarthritis. There have also been reports of knee pain and other symptoms, and poor quality of life more than 5 years later. What’s not been known until now, however, is what happens with even longer term follow-up, said Dr. Filbay, a postdoctoral research fellow in sport, exercise, and osteoarthritis at the University of Oxford, England.

The aims of the study were to compare patient-reported outcomes at 32-37-years’ follow-up against the general population, then to see if the baseline injury or treatment approach, or knee function 3-7 years after the initial injury had any influence on outcomes.

The study included 223 patients who were between aged 15 and 40 years at the time of the acute ACL injury between 1980 and 1985 and who had been seen within 2 weeks of ACL rupture at Linköping University Hospital in Linköping, Sweden. Patients had been allocated to early surgical or non-surgical treatment based on having an odd or even birth year. They had then been assessed 3-7 years later using a variety of tests to determine the strength of their quadriceps and hamstrings and the ability to hop on one leg.

All patients were then invited 32-37 years later after the initial injury to complete questionnaires and undergo clinical examination and X-rays. Only four people declined and 38 did not answer, leaving 181 (81%) people who agreed to participate and complete the Knee injury and Osteoarthritis Outcome Score (KOOS) and the ACL quality of life questionnaire (ACL-QOL).

 

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

 

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

 

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.

 

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

Furthermore, of 136 patients who underwent X-rays that were graded by an experienced radiologist, 6% had knee replacements and about 70% had developed knee OA.

The link between OA and ACL injury is not new, with prior estimates suggesting that up to half of all patients with ACL injury develop OA within 10 years of the injury, said Stephanie Filbay, PhD, who presented the results of the study at the World Congress on Osteoarthritis. There have also been reports of knee pain and other symptoms, and poor quality of life more than 5 years later. What’s not been known until now, however, is what happens with even longer term follow-up, said Dr. Filbay, a postdoctoral research fellow in sport, exercise, and osteoarthritis at the University of Oxford, England.

The aims of the study were to compare patient-reported outcomes at 32-37-years’ follow-up against the general population, then to see if the baseline injury or treatment approach, or knee function 3-7 years after the initial injury had any influence on outcomes.

The study included 223 patients who were between aged 15 and 40 years at the time of the acute ACL injury between 1980 and 1985 and who had been seen within 2 weeks of ACL rupture at Linköping University Hospital in Linköping, Sweden. Patients had been allocated to early surgical or non-surgical treatment based on having an odd or even birth year. They had then been assessed 3-7 years later using a variety of tests to determine the strength of their quadriceps and hamstrings and the ability to hop on one leg.

All patients were then invited 32-37 years later after the initial injury to complete questionnaires and undergo clinical examination and X-rays. Only four people declined and 38 did not answer, leaving 181 (81%) people who agreed to participate and complete the Knee injury and Osteoarthritis Outcome Score (KOOS) and the ACL quality of life questionnaire (ACL-QOL).

 

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

 

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

 

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.

 

LIVERPOOL, ENGLAND – Decades after they were sustained, acute knee injuries caused clinically significant impairments in patient-reported outcomes, as well as upped the risk for knee osteoarthritis (OA) in an observational study.

Results of the study, which followed up individuals 32-37 years after they were treated for a ruptured anterior cruciate ligament (ACL) injury between 1980 and 1985, showed that, compared with the general population, they experienced greater levels of knee pain, participated less in physical activities, and had a reduced quality of life.

Sara Freeman/MDEdge News

Furthermore, of 136 patients who underwent X-rays that were graded by an experienced radiologist, 6% had knee replacements and about 70% had developed knee OA.

The link between OA and ACL injury is not new, with prior estimates suggesting that up to half of all patients with ACL injury develop OA within 10 years of the injury, said Stephanie Filbay, PhD, who presented the results of the study at the World Congress on Osteoarthritis. There have also been reports of knee pain and other symptoms, and poor quality of life more than 5 years later. What’s not been known until now, however, is what happens with even longer term follow-up, said Dr. Filbay, a postdoctoral research fellow in sport, exercise, and osteoarthritis at the University of Oxford, England.

The aims of the study were to compare patient-reported outcomes at 32-37-years’ follow-up against the general population, then to see if the baseline injury or treatment approach, or knee function 3-7 years after the initial injury had any influence on outcomes.

The study included 223 patients who were between aged 15 and 40 years at the time of the acute ACL injury between 1980 and 1985 and who had been seen within 2 weeks of ACL rupture at Linköping University Hospital in Linköping, Sweden. Patients had been allocated to early surgical or non-surgical treatment based on having an odd or even birth year. They had then been assessed 3-7 years later using a variety of tests to determine the strength of their quadriceps and hamstrings and the ability to hop on one leg.

All patients were then invited 32-37 years later after the initial injury to complete questionnaires and undergo clinical examination and X-rays. Only four people declined and 38 did not answer, leaving 181 (81%) people who agreed to participate and complete the Knee injury and Osteoarthritis Outcome Score (KOOS) and the ACL quality of life questionnaire (ACL-QOL).

 

The average age of participants at follow-up was 59 years (range, 47-74 years); 30% were female. 58% of all patients had been treated non-surgically initially, and 38% remained non-surgically treated at the longterm follow-up. At baseline, 58% had a meniscus injury.

Compared with an age- and sex-matched Swedish population, patients with ACL injuries had a lower KOOS for pain, sport/recreational activities, and quality of life. For example, KOOS for knee pain was around 65-70 for those with prior ACL injuries, compared with 80-90 for those without ACL injuries, where 100 indicates the best outcome or least pain and zero the worst.

KOOS was not affected by whether or not patients had initial ACL surgery or surgery at any point in their follow up. It also did not appear to matter if patients had a meniscal injury at baseline or not.

Quadriceps and hamstring strength at the 3-7 year postinjury assessment did not affect the longterm KOOS, but the ability to hop on one leg did: Those who were not able to hop on one leg for more than 90% of the time on the unaffected limb at the 3-7 years follow-up had worse pain, symptoms, function, and quality of life at the longterm follow-up point.

 

With regards to OA, “overall, more than one in two individuals had Kellgren-Lawrence grade 4 that could be considered severe radiographic changes in at least one compartment,” Dr. Filbay said at the meeting, which is sponsored by the Osteoarthritis Research Society International.

Severe radiographic changes were most common in the tibiofemoral joint, with around 47% having Kellgren-Lawrence (KL) grade 4. About 35% of tibiofemoral joints and about 60% of patellofemoral joints were KL grade 1.

Interestingly, different factors were found to be associated with OA in the tibiofemoral and patellofemoral joints, according to Dr. Filbay. Patients who had been treated non-surgically, whether initially or at any time during the 32-37 year follow-up, were more likely to have tibiofemoral OA, whereas those who had been treated surgically tended to have patellofemoral OA.

“Perhaps not surprisingly, meniscal injury at baseline was related to a higher percentage of tibiofemoral OA at long-term follow-up,” Dr. Filbay said.

 

Another finding was that patients with weaker hamstrings 3-7 years after the injury were more likely to develop patellofemoral joint OA.

Dr. Filbay had no disclosures.

[email protected]

SOURCE: Filbay S, et al. Osteoarthritis Cartilage 2018:26(1):S52-3. Abstract 80.