Osteoarthritis

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

People with osteoarthritis who go on to have a total or partial knee replacement do not appear to have an increased risk of all-cause mortality, but the jury is still out on whether they gain any improvement, a study showed.

In their research published in the Annals of the Rheumatic Diseases [2016 May 17. doi: 10.1136/annrheumdis-2016-209167], Dr. Devyani Misra of Boston University and colleagues noted that knee replacement (KR) was thought to decrease long-term mortality risk because of the relief from pain and improvement in function that typically comes with surgery. However, studies on the topic had been conflicting, largely because of the challenges associated with studying mortality with KR surgery in observational settings.

©Nandyphotos/Thinkstock

In the current study the research team sought to evaluate the relation of KR to the risk of all-cause mortality among subjects with knee OA, while at the same time giving particular attention to “potential sources of confounding bias that may account for [the] effect of KR on mortality.”

Using patient data from the U.K. primary care electronic database THIN, the investigators compared the risk of mortality among 14,042 subjects who had OA, were aged 50-89 years old, and had had or had not had KR.

They discovered a strong protective effect of KR on all-cause long-term mortality risk, particularly among the adults over 63 years of age.

For example, people who had undergone KR had a 28% lower risk of mortality than did non-KR subjects (hazard ratio, 0.72; 95% confidence interval, 0.66-0.78).

In the overall propensity score–matched study sample, crude mortality per 1,000 person-years (total person-years) for the KR and non-KR cohorts were 19 (61,015) and 25 (58,294), respectively.

However, despite their best efforts, the researchers said the results showed evidence of residual confounding.

“For example, the observation of improved survival immediately after KR, despite the expectation of potential short-term increased postoperative mortality risk supports the presence of residual confounding,” they wrote.

Another finding suggestive of confounding was that the protective effect was seen only in older patients (over 63) when the authors stratified study participants by age.

“While it is possible that survival benefit seen in older patients with KR is a true effect because it is in this group that greater physical activity is particularly important to survival, more likely it is a result of residual confounding because subject selection is rigorous in this age group due to vulnerability,” the authors wrote.

They concluded that knee replacement “did not appear to be associated with an increased risk of all-cause mortality.”

“While we cannot rule out that KR may potentially reduce the risk of mortality over the long term, the true extent of that potential benefit is difficult to discern due to confounding by indication in observational studies using administrative data or electronic health records,” they added.

This study was funded by the Arthritis Foundation Postdoctoral Fellowship Award, the ACR Rheumatology Research Foundation Investigator Award, and a Boston University scholarship grant.

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

LONDON – Tumor necrosis factor may play a role in erosive hand osteoarthritis, and treatments such as etanercept that target this cytokine may help prevent progression of the condition, according to the results of two studies presented at the European Congress of Rheumatology.

In one of the studies, immunoscintigraphic detection of radiolabeled certolizumab pegol was used to show that tumor necrosis factor (TNF) was present in swollen finger joints. In another study, researchers looked to see if treatment with etanercept would have any specific effects on the joints of patients with erosive hand osteoarthritis (OA) and performed a separate analysis of the potential effect on synovitis and the effect on bone marrow lesions.

“We previously had the idea that TNF is an important cytokine in the pathogenesis of erosive [hand] osteoarthritis; but there have been no animal studies, and it’s very difficult to take biopsies or fluid aspiration from these small finger joints,” Dr. Ruth Wittoek, a staff rheumatologist at Ghent University Hospital in Belgium and a coauthor of all three studies, explained in a precongress interview. “We needed to look for other possibilities to really identify the presence of TNF in those affected joints.”

Dr. Wittoek and her associates used immunoscintigraphy to take static images of both hands of five patients with erosive OA immediately (less than 15 minutes) after administration of radiolabeled certolizumab pegol (early phase) and 4-6 hours following the injection (late phase).

The patients studied had erosive OA for a median of 8.4 years, and their median age was 55.6 years. All patients underwent clinical examination for presence of tenderness and palpable swelling of the joints and ultrasound 1 day prior to undergoing immunoscintigraphy.

All 18 interphalangeal (IP) finger joints were scored according to the anatomical phase scoring system on x-ray, and 90 IP finger joints were studied in total. The uptake of radiolabeled certolizumab pegol was semiquantitatively described as being absent, weak, or strong.

During the early phase following administration, uptake of the radiolabeled TNF inhibitor was seen in seven (7.8%) joints, although the uptake was described as weak in all cases. The radiolabeled TNF inhibitor was seen in 24 (26.7%) joints during the late phase following administration, with five instances described as strong uptake and the remaining 19 instances being weak uptake. No uptake of the radiolabeled TNF inhibitor was seen in metacarpophalangeal joints.

Uptake of the radiolabeled TNF inhibitor was linked to signs of disease activity, including tender, swollen, and radiographically active joints.

Late uptake was present in 12 (36.4%) of 33 tender joints and in 12 (21.1%) of 57 nontender joints (odds ratio, 2.1; 95% confidence interval, 0.8-5.6; P was nonsignificant).

The relationship was most pronounced with palpable joint swelling: Late uptake was present in 14 (61%) of 23 swollen joints and 10 (14.9%) of 67 nonswollen joints (OR, 8.9; 95% CI, 3.3-26.0; P less than .001).

Late uptake was present in 18 (29%) of 62 sonographically active joints (defined as any presence of effusion or synovial proliferation) but just 6 (21.4%) of 28 noninflamed joints (OR, 1.5; 95% CI, 0.5-4.3; P was nonsignificant).

Uptake of the radiolabeled TNF inhibitor was observed in all anatomical phases of erosive hand OA, Dr. Wittoek noted, but the strongest association was found during the final remodeling (R) phase.

“Soft-tissue swelling strongly correlated with uptake of certolizumab, meaning in these joints a lot of TNF was present,” Dr. Wittoek said. “These data further solidify the rationale for cytokine-directed therapies in erosive OA.”

Although the data provide proof of concept that TNF may be involved in erosive hand OA, the lack of a control tracer was noted as a limitation of the study after the investigator’s presentation. Dr. Wittoek conceded that it would be interesting to examine that in a future study.

So, if TNF is present, what effect does anti-TNF therapy have on the joints in erosive hand OA?

That question was addressed in a multicenter, double-blind, randomized, placebo-controlled trial involving 90 patients who were randomized to receive either 50 mg of subcutaneous etanercept weekly for 24 weeks, then 25 mg weekly for the remainder of 1 year (45 patients), or placebo (45 patients). Participants were a mean age of 60 years, 81% were women, and 96% fulfilled the American College of Rheumatology hand OA criteria.

“Synovial inflammation is often present in erosive hand OA; moreover, synovitis is associated with pain and with structural damage after around 2 and a half years,” the lead study author, Dr. Margreet Kloppenburg, a professor of rheumatology at Leiden University Medical Centre in the Netherlands, said in an interview.

“Therefore, we wanted to know whether blocking of synovial inflammation by a well-known drug such as etanercept would also have a positive effect on outcomes in erosive hand OA,” Dr. Kloppenburg explained.

The primary outcome measure was the level of OA pain assessed on a visual analog scale (VAS) at 24 weeks.

Secondary endpoints included assessment of hand function, quality of life, the number of tender joints, and grip strength after 4, 8, 12, 24, and 36 weeks, and after 1 year. Radiographic progression of IP joints was scored blindly at baseline, 24 weeks, and 1 year following the quantitative Ghent University Scoring System (GUSS). VAS pain was compared between treatment groups at 24 weeks and 1 year in intention-to-treat analyses.

Although etanercept was not superior to placebo on VAS pain at 24 weeks, it was superior to placebo both on pain and structural damage assessed by GUSS in the symptomatic and inflammatory patients who completed the study. The drug was especially effective in joints with signs of inflammation.

Overall, VAS pain in all patients decreased by 24.8 mm (95% CI, –29.2 to –20.5; P less than .001) at 24 weeks. In intention-to-treat analysis, differences in pain between the groups were in favor of etanercept but did not reach statistical significance. The per-protocol analysis of GUSS showed a mean difference in favor of etanercept, indicating more remodeling in the etanercept group.

Additional analyses showed an interaction between soft swelling/erythema and etanercept treatment on GUSS, resulting in a statistically significant (P less than .05) mean difference between the two treatment groups. More patients dropped out on placebo than on etanercept (six vs. three) because of inefficacy, whereas more dropped out on etanercept than on placebo (six vs. one) because of adverse effects.

“Synovial inflammation is an interesting target for treatment in OA patients with an inflammatory hand osteoarthritis phenotype,” Dr. Kloppenburg said.

A separate analysis of the same multicenter study suggests that etanercept is effective in inhibiting bone marrow lesions (BMLs) in patients with erosive hand OA.

The researchers studied 20 participants with symptomatic erosive OA with clinical and ultrasonographic signs of inflammation in at least one IP joint. The patients underwent contrast-enhanced MRI of the eight distal and proximal IP joints of one hand at baseline and 1 year. Images were scored for synovitis and BMLs (0-3 per joint, total score 0-24), blinded for patient characteristics.

Radiographs of the same hand were scored according to the Verbruggen-Veys system. Logistic regression was used to associate the presence of an MRI feature in a joint with being in an erosive versus nonerosive anatomical phase.

“Although erosive hand OA is a condition with a high disease burden, no disease-modifying treatments are available yet,” explained Féline Kroon, a PhD student in the department of rheumatology at Leiden University Medical Center in the Netherlands, in an interview. “Research to find a new form of therapy is partly hindered by our limited knowledge on the pathophysiology of the disease.”

However, “new imaging modalities like MRI enable us to study the pathophysiology of erosive OA more closely,” she said. “This study also gave us the unique opportunity to investigate whether anti-TNF, which is known to lead to clinical improvement and improvement of inflammatory lesions on MRI in other rheumatic diseases like rheumatoid arthritis, might also be effective in erosive OA.”

The presence of BMLs, but not synovitis, was associated with the presence of an erosive anatomical phase in a joint, and treatment with etanercept appeared to be effective in inhibiting these lesions. That suggests a role for TNF in the pathophysiology of erosive OA.

The inhibitory effect of etanercept on BMLs was more pronounced in IP joints with severe synovitis at baseline, suggesting that inflamed synovial tissue could be a source of TNF production in erosive OA.

The total synovitis score was similar at baseline and 1 year in both study groups. For BMLs, the median total score at baseline was 5.4 (range 2-9) and 7.0 (0-9) at 1 year in the placebo group, versus 4.5 (3-9) and 3.7 (0-8), respectively, in the etanercept group.

The presence of BMLs was associated with being in the erosive and remodeling anatomical phases of erosive hand OA. Synovitis was not associated with those phases.

“We think that TNF-alpha plays a role in the pathophysiology of erosive OA via an effect on the subchondral bone,” Ms. Kroon said. “Because we saw that the beneficial effect of etanercept on BMLs was more pronounced in joints with synovitis at baseline, we think that, in an inflamed synovial hand joint, an interaction takes place between synovium and subchondral bone, which could be influenced by blocking TNF.”

Pfizer and UCB supported the investigator-initiated studies and provided the study drugs. Dr. Kloppenburg has received lecturing, consultancy, and investigator fees or grants from AbbVie, APPROACH, GlaxoSmithKline, Levicept, Pfizer, Servier, and UCB, all paid to her institution. All other authors declared no conflicts of interests.

[email protected]

Adding telephone coaching to a home-based physiotherapist-prescribed activity program does not increase the pain and function benefits of such a program alone in knee osteoarthritis, a randomized controlled trial shows.

Kim L. Bennell, Ph.D., and her associates recruited volunteers who were aged 50 years and older, had knee pain rated at 4 or higher on an 11-point scale, and were classified as sedentary. One group participated in both coaching and the home-based physiotherapy program; the other participated in the home-based physiotherapy program alone.

©decade3d/Thinkstock

Overall,142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements. In the 6-month outcomes, no significance differences were found between the two groups in average pain (mean difference, 0.4 units) or in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function (1.8 units). In addition, there was no change between group differences observed at either 12 or 18 months. At 6 months, however, both groups showed large significant and clinically important improvements from baseline in the primary outcomes of pain and function, reported Dr. Bennell of the Centre for Health, Exercise and Sports Medicine at the University of Melbourne.

Reseachers also examined secondary outcomes and found there was no significant difference for change in numeric rating scale walking pain, WOMAC pain, or quality-of-life scores at any time.

“Improving exercise adherence was an aim of our coaching intervention given that adherence is positively linked to clinical outcomes in knee OA,” the reseachers concluded. “Our study provides novel information about the effects of telephone coaching alongside a physiotherapy prescribed physical activity and exercise program and extends the limited research in telephone coaching for OA.”

Read the full study in Arthritis Care & Research (doi: 10.1002/acr.22915).

[email protected]

Adding telephone coaching to a home-based physiotherapist-prescribed activity program does not increase the pain and function benefits of such a program alone in knee osteoarthritis, a randomized controlled trial shows.

Kim L. Bennell, Ph.D., and her associates recruited volunteers who were aged 50 years and older, had knee pain rated at 4 or higher on an 11-point scale, and were classified as sedentary. One group participated in both coaching and the home-based physiotherapy program; the other participated in the home-based physiotherapy program alone.

©decade3d/Thinkstock

Overall,142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements. In the 6-month outcomes, no significance differences were found between the two groups in average pain (mean difference, 0.4 units) or in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function (1.8 units). In addition, there was no change between group differences observed at either 12 or 18 months. At 6 months, however, both groups showed large significant and clinically important improvements from baseline in the primary outcomes of pain and function, reported Dr. Bennell of the Centre for Health, Exercise and Sports Medicine at the University of Melbourne.

Reseachers also examined secondary outcomes and found there was no significant difference for change in numeric rating scale walking pain, WOMAC pain, or quality-of-life scores at any time.

“Improving exercise adherence was an aim of our coaching intervention given that adherence is positively linked to clinical outcomes in knee OA,” the reseachers concluded. “Our study provides novel information about the effects of telephone coaching alongside a physiotherapy prescribed physical activity and exercise program and extends the limited research in telephone coaching for OA.”

Read the full study in Arthritis Care & Research (doi: 10.1002/acr.22915).

[email protected]

Adding telephone coaching to a home-based physiotherapist-prescribed activity program does not increase the pain and function benefits of such a program alone in knee osteoarthritis, a randomized controlled trial shows.

Kim L. Bennell, Ph.D., and her associates recruited volunteers who were aged 50 years and older, had knee pain rated at 4 or higher on an 11-point scale, and were classified as sedentary. One group participated in both coaching and the home-based physiotherapy program; the other participated in the home-based physiotherapy program alone.

©decade3d/Thinkstock

Overall,142 (85%), 136 (81%), and 128 (76%) participants completed 6-, 12-, and 18-month measurements. In the 6-month outcomes, no significance differences were found between the two groups in average pain (mean difference, 0.4 units) or in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function (1.8 units). In addition, there was no change between group differences observed at either 12 or 18 months. At 6 months, however, both groups showed large significant and clinically important improvements from baseline in the primary outcomes of pain and function, reported Dr. Bennell of the Centre for Health, Exercise and Sports Medicine at the University of Melbourne.

Reseachers also examined secondary outcomes and found there was no significant difference for change in numeric rating scale walking pain, WOMAC pain, or quality-of-life scores at any time.

“Improving exercise adherence was an aim of our coaching intervention given that adherence is positively linked to clinical outcomes in knee OA,” the reseachers concluded. “Our study provides novel information about the effects of telephone coaching alongside a physiotherapy prescribed physical activity and exercise program and extends the limited research in telephone coaching for OA.”

Read the full study in Arthritis Care & Research (doi: 10.1002/acr.22915).

[email protected]

GLASGOW – Older adults are more than seven times as likely to develop knee osteoarthritis if they had anterior knee pain as adolescents, according to the results of a case-control study.

The adjusted odds ratio for patellofemoral osteoarthritis (PFOA) was 7.5 if there was prior adolescent anterior knee pain. Although the 95% confidence interval was wide (1.51-36.94) the association was significant (P = .014). Adjustment had been made for the potential confounding factors of previous patellar dislocation, prior surgery, and patient-reported knee instability; before this adjustment the OR was 20.2 (95% CI, 3.34-11.67).

©pixologicstudio/Thinkstock

Patellar dislocation during adolescence also was found to be a significant risk factor for later PFOA (aOR, 3.2; 95% CI, 1.25-9.18; P = .016).

“Adolescent anterior knee pain represents a constellation of symptoms and had always been thought of as benign and self-limiting,” Henry Conchie, a medical student at the University of Bristol (England), said at the British Society for Rheumatology annual conference.

“I think the take-home message from our research is really that this traditional view of benign pathology associated with adolescent anterior knee pain and patellar dislocation must be challenged and when seen in clinical practice we now encourage the acknowledgment of the potentially severe consequences in the future,” Mr. Conchie said.

A link between adolescent anterior knee pain and later PFOA has previously been suggested but there are few data to support this observation, he explained. So the aim of the current study was to look at this in more detail in a group of patients from the knee arthroplasty database at Southmead Hospital in Bristol.

Questionnaires that asked about a variety of symptoms and knee pain were sent to 190 patients in the database who had undergone patellofemoral arthroplasty and so had severe, isolated, and radiologically confirmed PFOA. Questionnaires also were sent to 445 patients who had undergone arthroplasty for unicompartmental tibiofemoral arthritis to serve as the control group.

A subanalysis was performed to look at the mean age of the first dislocation and the investigators found that patients with PFOA were likely to be much younger than controls, with a 44-year difference observed between the groups.

“This adds some weight to the theory that this process [PFOA] begins much earlier than once thought – at a younger age,” Mr. Conchie suggested.

The study subjects were surveyed 1-4 years after their operation, so patient recall could have affected the results, but the use of the unicompartmental tibiofemoral arthritis patients as controls should have reduced this potential bias, he said. The fact that they had gone through an arthroplasty meant that they would have had very similar experiences to the PFOA group in terms of pain.

Although only severe OA cases and arthritis controls were used, the team believes that the findings are robust as these were clearly defined patient groups, albeit at the end of the disease spectrum.

“Thought can now turn to etiological mechanisms underlying these relationships, and I think it is likely that anatomical etiologies such as patellar outer and trochlear dysplasia can define both the pain and instability in youth as well as the patellofemoral osteoarthritis in later life,” Mr. Conchie proposed. Further research to look at this would be needed in future.

During the Q&A following his presentation, Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, commented that she had looked at the persistence of pain in patients with adolescent anterior knee pain some years ago and found that, 10-20 years later, 60% were still experiencing pain.

The chair of the session, Dr. Joyce Davidson of the Royal Hospital for Sick Children in Glasgow, summed up by saying: “I think we do see lots of patients and maybe we just need to be aware that this may not be as benign as we think, and certainly we should be looking for abnormal patellae and being very aware of it in young people.”

Mr. Conchie and his coauthors had nothing to disclose.

GLASGOW – Older adults are more than seven times as likely to develop knee osteoarthritis if they had anterior knee pain as adolescents, according to the results of a case-control study.

The adjusted odds ratio for patellofemoral osteoarthritis (PFOA) was 7.5 if there was prior adolescent anterior knee pain. Although the 95% confidence interval was wide (1.51-36.94) the association was significant (P = .014). Adjustment had been made for the potential confounding factors of previous patellar dislocation, prior surgery, and patient-reported knee instability; before this adjustment the OR was 20.2 (95% CI, 3.34-11.67).

©pixologicstudio/Thinkstock

Patellar dislocation during adolescence also was found to be a significant risk factor for later PFOA (aOR, 3.2; 95% CI, 1.25-9.18; P = .016).

“Adolescent anterior knee pain represents a constellation of symptoms and had always been thought of as benign and self-limiting,” Henry Conchie, a medical student at the University of Bristol (England), said at the British Society for Rheumatology annual conference.

“I think the take-home message from our research is really that this traditional view of benign pathology associated with adolescent anterior knee pain and patellar dislocation must be challenged and when seen in clinical practice we now encourage the acknowledgment of the potentially severe consequences in the future,” Mr. Conchie said.

A link between adolescent anterior knee pain and later PFOA has previously been suggested but there are few data to support this observation, he explained. So the aim of the current study was to look at this in more detail in a group of patients from the knee arthroplasty database at Southmead Hospital in Bristol.

Questionnaires that asked about a variety of symptoms and knee pain were sent to 190 patients in the database who had undergone patellofemoral arthroplasty and so had severe, isolated, and radiologically confirmed PFOA. Questionnaires also were sent to 445 patients who had undergone arthroplasty for unicompartmental tibiofemoral arthritis to serve as the control group.

A subanalysis was performed to look at the mean age of the first dislocation and the investigators found that patients with PFOA were likely to be much younger than controls, with a 44-year difference observed between the groups.

“This adds some weight to the theory that this process [PFOA] begins much earlier than once thought – at a younger age,” Mr. Conchie suggested.

The study subjects were surveyed 1-4 years after their operation, so patient recall could have affected the results, but the use of the unicompartmental tibiofemoral arthritis patients as controls should have reduced this potential bias, he said. The fact that they had gone through an arthroplasty meant that they would have had very similar experiences to the PFOA group in terms of pain.

Although only severe OA cases and arthritis controls were used, the team believes that the findings are robust as these were clearly defined patient groups, albeit at the end of the disease spectrum.

“Thought can now turn to etiological mechanisms underlying these relationships, and I think it is likely that anatomical etiologies such as patellar outer and trochlear dysplasia can define both the pain and instability in youth as well as the patellofemoral osteoarthritis in later life,” Mr. Conchie proposed. Further research to look at this would be needed in future.

During the Q&A following his presentation, Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, commented that she had looked at the persistence of pain in patients with adolescent anterior knee pain some years ago and found that, 10-20 years later, 60% were still experiencing pain.

The chair of the session, Dr. Joyce Davidson of the Royal Hospital for Sick Children in Glasgow, summed up by saying: “I think we do see lots of patients and maybe we just need to be aware that this may not be as benign as we think, and certainly we should be looking for abnormal patellae and being very aware of it in young people.”

Mr. Conchie and his coauthors had nothing to disclose.

GLASGOW – Older adults are more than seven times as likely to develop knee osteoarthritis if they had anterior knee pain as adolescents, according to the results of a case-control study.

The adjusted odds ratio for patellofemoral osteoarthritis (PFOA) was 7.5 if there was prior adolescent anterior knee pain. Although the 95% confidence interval was wide (1.51-36.94) the association was significant (P = .014). Adjustment had been made for the potential confounding factors of previous patellar dislocation, prior surgery, and patient-reported knee instability; before this adjustment the OR was 20.2 (95% CI, 3.34-11.67).

©pixologicstudio/Thinkstock

Patellar dislocation during adolescence also was found to be a significant risk factor for later PFOA (aOR, 3.2; 95% CI, 1.25-9.18; P = .016).

“Adolescent anterior knee pain represents a constellation of symptoms and had always been thought of as benign and self-limiting,” Henry Conchie, a medical student at the University of Bristol (England), said at the British Society for Rheumatology annual conference.

“I think the take-home message from our research is really that this traditional view of benign pathology associated with adolescent anterior knee pain and patellar dislocation must be challenged and when seen in clinical practice we now encourage the acknowledgment of the potentially severe consequences in the future,” Mr. Conchie said.

A link between adolescent anterior knee pain and later PFOA has previously been suggested but there are few data to support this observation, he explained. So the aim of the current study was to look at this in more detail in a group of patients from the knee arthroplasty database at Southmead Hospital in Bristol.

Questionnaires that asked about a variety of symptoms and knee pain were sent to 190 patients in the database who had undergone patellofemoral arthroplasty and so had severe, isolated, and radiologically confirmed PFOA. Questionnaires also were sent to 445 patients who had undergone arthroplasty for unicompartmental tibiofemoral arthritis to serve as the control group.

A subanalysis was performed to look at the mean age of the first dislocation and the investigators found that patients with PFOA were likely to be much younger than controls, with a 44-year difference observed between the groups.

“This adds some weight to the theory that this process [PFOA] begins much earlier than once thought – at a younger age,” Mr. Conchie suggested.

The study subjects were surveyed 1-4 years after their operation, so patient recall could have affected the results, but the use of the unicompartmental tibiofemoral arthritis patients as controls should have reduced this potential bias, he said. The fact that they had gone through an arthroplasty meant that they would have had very similar experiences to the PFOA group in terms of pain.

Although only severe OA cases and arthritis controls were used, the team believes that the findings are robust as these were clearly defined patient groups, albeit at the end of the disease spectrum.

“Thought can now turn to etiological mechanisms underlying these relationships, and I think it is likely that anatomical etiologies such as patellar outer and trochlear dysplasia can define both the pain and instability in youth as well as the patellofemoral osteoarthritis in later life,” Mr. Conchie proposed. Further research to look at this would be needed in future.

During the Q&A following his presentation, Dr. Eileen Baildam of Alder Hey Children’s Hospital in Liverpool, England, commented that she had looked at the persistence of pain in patients with adolescent anterior knee pain some years ago and found that, 10-20 years later, 60% were still experiencing pain.

The chair of the session, Dr. Joyce Davidson of the Royal Hospital for Sick Children in Glasgow, summed up by saying: “I think we do see lots of patients and maybe we just need to be aware that this may not be as benign as we think, and certainly we should be looking for abnormal patellae and being very aware of it in young people.”

Mr. Conchie and his coauthors had nothing to disclose.

Treatment with opioids is not cost effective in osteoarthritis patients without comorbidities, according to Savannah R. Smith and her associates.

When a 10% reduction in total knee arthroplasty (TKA) effectiveness from opioid-based therapies was assumed, tramadol therapy delayed TKA by 7 years and tramadol plus oxycodone therapy delayed TKA by 9 years. Opioid-based therapy reduced primary TKA utilization by 4% for tramadol and by 10% for tramadol plus oxycodone, and reduced revision TKA use by 23% and 39%, respectively.

©decade3d/Thinkstock

While both opioid-based therapies reduced dependence on TKA, treatment was more expensive and it reduced quality of life, compared with an opioid-sparing therapy. For a 60-year-old OA patient for whom TKA was not an option, the incremental cost-effectiveness ratio for tramadol was $39,600 per quality-adjusted life-year, compared with a therapy without opioids, and the incremental cost-effectiveness ratio for tramadol plus oxycodone was $116,800 per quality-adjusted life-year.

“Given the risk of diversion and its associated cost for potent opioids, policy makers may consider limiting the use of potent opioids in knee OA patients. From a cost-effectiveness standpoint, both opioid-based strategies led to higher costs without providing additional benefits, unless patients were unwilling or unable to undergo TKA later,” the investigators noted.

Find the full study in Arthritis Care and Research (doi: 10.1002/acr.22916).

[email protected]

Treatment with opioids is not cost effective in osteoarthritis patients without comorbidities, according to Savannah R. Smith and her associates.

When a 10% reduction in total knee arthroplasty (TKA) effectiveness from opioid-based therapies was assumed, tramadol therapy delayed TKA by 7 years and tramadol plus oxycodone therapy delayed TKA by 9 years. Opioid-based therapy reduced primary TKA utilization by 4% for tramadol and by 10% for tramadol plus oxycodone, and reduced revision TKA use by 23% and 39%, respectively.

©decade3d/Thinkstock

While both opioid-based therapies reduced dependence on TKA, treatment was more expensive and it reduced quality of life, compared with an opioid-sparing therapy. For a 60-year-old OA patient for whom TKA was not an option, the incremental cost-effectiveness ratio for tramadol was $39,600 per quality-adjusted life-year, compared with a therapy without opioids, and the incremental cost-effectiveness ratio for tramadol plus oxycodone was $116,800 per quality-adjusted life-year.

“Given the risk of diversion and its associated cost for potent opioids, policy makers may consider limiting the use of potent opioids in knee OA patients. From a cost-effectiveness standpoint, both opioid-based strategies led to higher costs without providing additional benefits, unless patients were unwilling or unable to undergo TKA later,” the investigators noted.

Find the full study in Arthritis Care and Research (doi: 10.1002/acr.22916).

[email protected]

Treatment with opioids is not cost effective in osteoarthritis patients without comorbidities, according to Savannah R. Smith and her associates.

When a 10% reduction in total knee arthroplasty (TKA) effectiveness from opioid-based therapies was assumed, tramadol therapy delayed TKA by 7 years and tramadol plus oxycodone therapy delayed TKA by 9 years. Opioid-based therapy reduced primary TKA utilization by 4% for tramadol and by 10% for tramadol plus oxycodone, and reduced revision TKA use by 23% and 39%, respectively.

©decade3d/Thinkstock

While both opioid-based therapies reduced dependence on TKA, treatment was more expensive and it reduced quality of life, compared with an opioid-sparing therapy. For a 60-year-old OA patient for whom TKA was not an option, the incremental cost-effectiveness ratio for tramadol was $39,600 per quality-adjusted life-year, compared with a therapy without opioids, and the incremental cost-effectiveness ratio for tramadol plus oxycodone was $116,800 per quality-adjusted life-year.

“Given the risk of diversion and its associated cost for potent opioids, policy makers may consider limiting the use of potent opioids in knee OA patients. From a cost-effectiveness standpoint, both opioid-based strategies led to higher costs without providing additional benefits, unless patients were unwilling or unable to undergo TKA later,” the investigators noted.

Find the full study in Arthritis Care and Research (doi: 10.1002/acr.22916).

[email protected]

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

AMSTERDAM – Results of separate U.S. and European studies hold promise that predictive blood tests for the diagnosis and progression of knee osteoarthritis could soon be developed.

Researchers at Duke University in Durham, N.C., and at the Hospital Universitario de A Coruña, Spain, reported their studies’ findings at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical trials are often statistically underpowered to measure progression of knee osteoarthritis, noted Dr. Virginia B. Kraus of Duke University, because of inefficient methods for identifying patients who would progress.

“This is because, with the exception of generalized OA, traditional risk factors are very poor predictors, and that includes age, gender, BMI [body mass index], knee pain, and baseline joint space width,” she explained. Radiographic changes and changes in Kellgren-Lawrence grade are often slow to appear and may only occur in a few subjects at a time. Imaging biomarkers have been identified but are a “rather expensive way of predicting progression,” Dr. Kraus said. There have been some associations between OA progression and biomarkers in the urine and serum, she said, but still not at a level that could be put to clinical use.

“We hypothesized that we could improve the utility of OA biomarkers by using a nonbiased, nontargeted [mass spectrometry] approach,” Dr. Kraus said, explaining that this allowed them to create a Multiple Reaction Monitoring (MRM) panel of 146 serum peptides that were based on analyses of serum, synovial fluid, and urine samples from knee OA radiographic progressors and nonprogressors. The MRM panel was used first to identify candidate biomarkers and then confirm their differential expression patterns, followed by a process of verifying and validating the selected serum biomarkers.

The main aim of the study was to look for serum biomarkers in data from the Prediction of Osteoarthritis Progression (POP) and Genetics of Generalized Osteoarthritis (GOGO) patient cohorts that would be highly predictive for knee OA progression, with a secondary aim to look at potential early diagnostic biomarkers. The investigators used data from 83 patients with symptomatic knee progression to search for prognostic biomarkers and 126 with symptoms but without knee progression to find diagnostic biomarkers. The mean age of patients was 64 years, and 82% were female. The mean BMI was 28 kg/m².

As expected, clinical predictors alone – age, gender, and BMI – had low predictive power for OA progression, with an area under the curve (AUC) of about 0.7. However, these clinical parameters in conjunction with a panel of 10 markers identified via MRM improved the AUC to 0.9 in the verification set and 0.8 in the validation set. For diagnosis, the AUC for clinical covariates alone was 0.8, but combined with a set of 19 MRM-identified markers, the AUC was 1.0 for the verification set and 0.9 for the validation set.

Dr. Kraus said that the serum peptide biomarkers identified from the MRM panel predicted that OA progression pathways would involve aggregation of cells, complement activation, cell movement of leukocytes, and cellular infiltration of leukocytes. The pathways predicted to be involved in a diagnosis of OA included skeletal function, cell movement, formation of filaments, cellular protrusions, and hemostasis.

“Results from this work in progress suggest that a select set of biomarkers from nontargeted analyses could significantly improve prediction of knee OA progression,” Dr. Kraus concluded. They also suggest a set of biomarkers could be used for diagnosis because of their distinction from those for progression, with one exception. Future work will look at whether the diagnostic panel could be used in patients with nonradiographic OA to potentially diagnose and perhaps help treat OA early before structural damage is apparent, she said.

The proteomics group at the Hospital Universitario de A Coruña collaborated with researchers at the KTH-Royal Institute of Technology in Stockholm and the University of Oxford (England) to also identify a serum protein biomarker panel that might prove useful for the diagnosis of OA.

Their study compared serum samples taken from 461 patients with knee OA with those taken from 412 patients with rheumatoid arthritis and 159 nonarthritic individuals. Serum samples from each of these groups were divided into a screening (n = 593) and a verification set (n = 439). The data were adjusted for variations in participant’s age, BMI, and gender.

In the screening phase, the investigators used an antibody suspension bead array composed of 174 antibodies to examine 78 protein targets to try to identify the best serum protein biomarker candidates. They replicated the findings in an adapted array of 79 antibodies and 34 protein targets and then used this array in the verification set of serum samples.

There were three proteins that could potentially differentiate patients with OA from controls and perhaps be used to diagnose OA. These were: complement 3, which is involved in inflammation; inter-alpha-trypsin inhibitor heavy chain I, which is involved in the stability of the extracellular matrix; and S100 calcium-binding protein A6, which has a role in chondrocyte differentiation and thus bone remodeling.

“Compared to rheumatoid arthritis patients, we observed that the level of complement 3 and inter-alpha-trypsin inhibitor heavy chain I are significantly increased in osteoarthritis patients,” said the presenting study author Lucía Maria Lourido Salas, PhD. “This suggests the potential of these two proteins as specific proteins for osteoarthritis,” she proposed. A further 28 proteins were found that might also help to differentiate OA from RA; 16 of these were increased and 12 decreased in OA patients. Together these 30 proteins could potentially help identify a specific serum protein signature of OA, Dr. Salas said.

Dr. Kraus and Dr. Salas did not report having any financial disclosures. Dr. Kraus’ research is funded by the Duke Biomarker Factory.

AMSTERDAM – There are four distinct patterns of pain in patients with early presumed hip osteoarthritis, and several factors could help identify patients most likely to experience more severe pain, according to analysis from a Dutch study.

The majority of the 545 patients included in the analysis from the Cohort Hip and Knee (CHECK) study experienced a low or a mild constant hip pain over a 5-year follow-up period (231 patients, 42.4%). Around one-quarter had moderate hip pain with moderate pain progression (132 patients, 24.2%), about one in six (88 patients, 16.1%) had moderate hip pain with moderate pain regression, and the remainder (94 patients, 17.2%) had constant, severe hip pain.

©iStock/Thinkstock

Factors associated with these pain trajectories included the level of education achieved, ability to cope with pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale, and pain experienced from internal rotation of the hip.

The findings were reported at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International. They were also published online in Osteoarthritis and Cartilage (2106 Feb 5. doi: 10.1016/j.joca.2015.11.023).

Although prior studies examined progression predictors in hip OA, none looked specifically at how pain changes over time, noted study author Dr. Alex Bastick of Erasmus University Medical Center, Rotterdam, the Netherlands. Thus, the current aim was to define the trajectory of hip pain among individuals with early symptoms of hip OA, and identify any baseline factors that might help clinicians predict which pain trajectory patients may follow.

The CHECK study is a 10-year nationwide cohort study of 1,002 participants in the Netherlands with assumed early symptomatic OA of the knee, hip, or both. For the current analysis, Dr. Bastick and his associates considered only those patients with hip pain or stiffness who had completed 5 years of follow-up. At baseline, the mean age of the total population was 55.7 years, and 81% of participants were female. About one-quarter (26%) of participants had a clinical OA diagnosis according to American College of Rheumatology criteria.

Baseline radiographic severity was not associated with the various pain trajectories identified, Dr. Bastick observed, but patients who had achieved a lower level of education were roughly three times more likely to experience severe pain than mild or low constant pain. Patients experiencing severe pain were more likely to use pain transformation as a coping strategy, have higher activity limitation scores, and experience painful internal hip rotation.

Because around 60% of patients follow the mild or moderately progressing pain trajectories, conservative treatment in the early stages of hip OA appears appropriate, Dr. Bastick and his associates suggested. Their findings highlight the importance of a physical examination, and that reassessment of clinical symptoms should perhaps be undertaken in the first year of follow-up.

“Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment,” the researchers proposed.

Reumafonds, the Dutch Arthritis Foundation, funded the study. Dr. Bastick did not have financial disclosures.

AMSTERDAM – There are four distinct patterns of pain in patients with early presumed hip osteoarthritis, and several factors could help identify patients most likely to experience more severe pain, according to analysis from a Dutch study.

The majority of the 545 patients included in the analysis from the Cohort Hip and Knee (CHECK) study experienced a low or a mild constant hip pain over a 5-year follow-up period (231 patients, 42.4%). Around one-quarter had moderate hip pain with moderate pain progression (132 patients, 24.2%), about one in six (88 patients, 16.1%) had moderate hip pain with moderate pain regression, and the remainder (94 patients, 17.2%) had constant, severe hip pain.

©iStock/Thinkstock

Factors associated with these pain trajectories included the level of education achieved, ability to cope with pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale, and pain experienced from internal rotation of the hip.

The findings were reported at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International. They were also published online in Osteoarthritis and Cartilage (2106 Feb 5. doi: 10.1016/j.joca.2015.11.023).

Although prior studies examined progression predictors in hip OA, none looked specifically at how pain changes over time, noted study author Dr. Alex Bastick of Erasmus University Medical Center, Rotterdam, the Netherlands. Thus, the current aim was to define the trajectory of hip pain among individuals with early symptoms of hip OA, and identify any baseline factors that might help clinicians predict which pain trajectory patients may follow.

The CHECK study is a 10-year nationwide cohort study of 1,002 participants in the Netherlands with assumed early symptomatic OA of the knee, hip, or both. For the current analysis, Dr. Bastick and his associates considered only those patients with hip pain or stiffness who had completed 5 years of follow-up. At baseline, the mean age of the total population was 55.7 years, and 81% of participants were female. About one-quarter (26%) of participants had a clinical OA diagnosis according to American College of Rheumatology criteria.

Baseline radiographic severity was not associated with the various pain trajectories identified, Dr. Bastick observed, but patients who had achieved a lower level of education were roughly three times more likely to experience severe pain than mild or low constant pain. Patients experiencing severe pain were more likely to use pain transformation as a coping strategy, have higher activity limitation scores, and experience painful internal hip rotation.

Because around 60% of patients follow the mild or moderately progressing pain trajectories, conservative treatment in the early stages of hip OA appears appropriate, Dr. Bastick and his associates suggested. Their findings highlight the importance of a physical examination, and that reassessment of clinical symptoms should perhaps be undertaken in the first year of follow-up.

“Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment,” the researchers proposed.

Reumafonds, the Dutch Arthritis Foundation, funded the study. Dr. Bastick did not have financial disclosures.

AMSTERDAM – There are four distinct patterns of pain in patients with early presumed hip osteoarthritis, and several factors could help identify patients most likely to experience more severe pain, according to analysis from a Dutch study.

The majority of the 545 patients included in the analysis from the Cohort Hip and Knee (CHECK) study experienced a low or a mild constant hip pain over a 5-year follow-up period (231 patients, 42.4%). Around one-quarter had moderate hip pain with moderate pain progression (132 patients, 24.2%), about one in six (88 patients, 16.1%) had moderate hip pain with moderate pain regression, and the remainder (94 patients, 17.2%) had constant, severe hip pain.

©iStock/Thinkstock

Factors associated with these pain trajectories included the level of education achieved, ability to cope with pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale, and pain experienced from internal rotation of the hip.

The findings were reported at the World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International. They were also published online in Osteoarthritis and Cartilage (2106 Feb 5. doi: 10.1016/j.joca.2015.11.023).

Although prior studies examined progression predictors in hip OA, none looked specifically at how pain changes over time, noted study author Dr. Alex Bastick of Erasmus University Medical Center, Rotterdam, the Netherlands. Thus, the current aim was to define the trajectory of hip pain among individuals with early symptoms of hip OA, and identify any baseline factors that might help clinicians predict which pain trajectory patients may follow.

The CHECK study is a 10-year nationwide cohort study of 1,002 participants in the Netherlands with assumed early symptomatic OA of the knee, hip, or both. For the current analysis, Dr. Bastick and his associates considered only those patients with hip pain or stiffness who had completed 5 years of follow-up. At baseline, the mean age of the total population was 55.7 years, and 81% of participants were female. About one-quarter (26%) of participants had a clinical OA diagnosis according to American College of Rheumatology criteria.

Baseline radiographic severity was not associated with the various pain trajectories identified, Dr. Bastick observed, but patients who had achieved a lower level of education were roughly three times more likely to experience severe pain than mild or low constant pain. Patients experiencing severe pain were more likely to use pain transformation as a coping strategy, have higher activity limitation scores, and experience painful internal hip rotation.

Because around 60% of patients follow the mild or moderately progressing pain trajectories, conservative treatment in the early stages of hip OA appears appropriate, Dr. Bastick and his associates suggested. Their findings highlight the importance of a physical examination, and that reassessment of clinical symptoms should perhaps be undertaken in the first year of follow-up.

“Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment,” the researchers proposed.

Reumafonds, the Dutch Arthritis Foundation, funded the study. Dr. Bastick did not have financial disclosures.