OARSI 2018

 

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.

rhnews@mdedge.com

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.

rhnews@mdedge.com

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.

rhnews@mdedge.com

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

 

LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.

“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.

Sara Freeman/MDedge News

The first systematic review conducted by Marc C. Hochberg 10 years ago (Clin Exp Rheumatol. 2008;26:S120–4) showed “moderate evidence” of increased mortality caused by OA, compared with the general population, Mr. Parmar elaborated at the congress, which is sponsored by the Osteoarthritis Research Society International.

Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.

However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).

“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.

So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.

 

The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.

At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.

Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.

“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.

 

After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.

“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”

Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).

“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.

 

“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.

Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.

Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”

The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.

SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.

 

LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.

“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.

Sara Freeman/MDedge News

The first systematic review conducted by Marc C. Hochberg 10 years ago (Clin Exp Rheumatol. 2008;26:S120–4) showed “moderate evidence” of increased mortality caused by OA, compared with the general population, Mr. Parmar elaborated at the congress, which is sponsored by the Osteoarthritis Research Society International.

Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.

However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).

“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.

So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.

 

The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.

At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.

Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.

“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.

 

After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.

“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”

Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).

“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.

 

“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.

Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.

Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”

The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.

SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.

 

LIVERPOOL, ENGLAND – Osteoarthritis is associated with an increased risk in mortality, but three factors – inactivity, low mood, and cognitive ability – could be important targets to reduce this risk, according to the results of a study presented at the World Congress on Osteoarthritis.

“There’s recently been increasing interest in whether osteoarthritis (OA) is associated with mortality as the literature has failed to find a consistent link,” said Simran Parmar, a third-year medical student at Keele University, Newcastle-Under-Lyme, U.K.

Sara Freeman/MDedge News

The first systematic review conducted by Marc C. Hochberg 10 years ago (Clin Exp Rheumatol. 2008;26:S120–4) showed “moderate evidence” of increased mortality caused by OA, compared with the general population, Mr. Parmar elaborated at the congress, which is sponsored by the Osteoarthritis Research Society International.

Three years later, data from another study (BMJ. 2011;342:d1165) suggested an increased risk, with standardized mortality ratios calculated to be 1.55 for all-cause mortality and 1.71 for cardiovascular-specific mortality when comparing those with OA to those without OA in the general population.

However, more recent meta-analyses, performed in 2016, have failed to show a relationship between mortality and OA (Semin Arthritis Rheum. 2016;46[2]:160–7; Sci Rep. 2016;6:24393).

“This could be because of heterogeneity among the studies,” Mr. Parmar reasoned, adding that there was still an unclear relationship between OA and mortality.

So the aim of the current study was not only to take another look at the association to determine its strength but also to see what factors might be mediating the association in order to perhaps explain why OA might be associated with an increased risk of death.

 

The analysis used data on more than 8,000 individuals participating in the NorStOP (North Staffordshire Osteoarthritis Project). This is a large, population-based, prospective cohort initiated in 2002 that includes adults aged 50 years or older who are registered at any of six general practices.

At baseline, the mean age of participants was 65 years, 51% were female, and just under 30% had OA. During 10 years of follow-up, 1,188 (14.7%) participants died.

Osteoarthritis was significantly associated with mortality in both unadjusted and adjusted analyses.

“For the average person presenting to general practice in North Staffordshire, there’s a 39.4% increased risk of mortality if they have osteoarthritis compared to if they don’t,” Mr. Parmar said.

 

After adjustment for potential confounding factors, such as age, NSAID use, and common comorbidities, the increased mortality risk remained, with around a 15% increased risk of death for those with OA versus those without.

“We proposed six different mediators of this relationship,” Mr. Parmar said. These were depression, anxiety, low walking frequency, cognitive impairment, insomnia, and obesity. “The reason we chose these is because they can be targets for therapy in primary care.”

Three mediators significantly affected the relationship: low walking frequency, depression, and cognitive impairment; the respective hazard ratios and 95% confidence intervals were 1.12 (1.09-1.15), 1.11 (1.08-1.15), and 1.06 (1.03-1.09).

“This tells us that these could possibly be on the pathway between osteoarthritis and mortality, and this could provide further evidence that they could be used for targeted therapy of osteoarthritis,” Mr. Parmar suggested.

 

“This type of mediation analysis has not been done in the osteoarthritis field before,” Mr. Parmar observed. He conceded that the mediators found might actually have contributed to the development of OA and that pain interference used in the definition of OA could have been caused by other factors.

Nevertheless, these data suggest that there may be actionable factors that could be used in primary care to reduce mortality in OA.

Mr. Parmar suggested that “encouraging physical activity and considering the impact of comorbidities can help reduce the risk of mortality in adults with osteoarthritis.”

The study was funded by Arthritis Research UK, the North Staffordshire Primary Care Consortium, and the Medical Research Council. Mr. Parmar had no conflicts of interest to disclose.

SOURCE: Parmar S et al. Osteoarthritis Cartilage. 2018;26(1):S14-15.