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Baseline CT scans predict lung fibrosis in SSc
Patients with newly diagnosed systemic sclerosis should have a high-resolution lung CT and pulmonary function tests, because when assessed together, their findings identify patients at high risk of interstitial lung disease, researchers say.
In a study of 305 patients with systemic sclerosis (SSc), a baseline high-resolution lung CT showing no fibrosis was highly predictive of a fibrosis free follow-up scan at 3 years, reported the researchers from Oslo (Norway) University Hospital. SSc associated interstitial lung–disease (SSc-ILD) typically has an insidious onset with subtle clinical symptoms, accoording to the authors in background information to the paper published in Arthritis & Rheumatology (Arthritis & Rheumatology 2015; [doi:10.1002/art.39166]).
This may explain why SSc-ILD is often diagnosed at an advanced stage, when extensive lung fibrosis is already present. “Better, and more targeted, strategies for SSc-ILD identification and risk stratification early in the disease course are therefore warranted,” they wrote.
In order to assess serial lung fibrosis measurements and paired pulmonary function tests (PFTs) as outcome prediction tools, the researchers prospectively analyzed both modalities at baseline and at an average of 3 years follow-up in 305 patients with SSc. The extent of fibrosis was scored on 10 sections from every high-resolution CT (HRCT) and expressed as a percentage of total lung volumes.
The researchers identified three groups of patients: More than 20% lung fibrosis (n=40), between 1%- 20% fibrosis (n=157), and no fibrosis (n=108). Results showed that all 108 patients who had no lung fibrosis at baseline remained free of fibrosis at a 3-year follow-up scan. These patients were predominantly female (88%) had limited (lc) SSc (84%), and were positive for anticentromere antibodies (ACA) (70%). They also had a high baseline decline in diffusing lung capacity for carbon monoxide (DLCO) that declined by 8.2%, the same degree as patients with lung fibrosis.
“This finding emphasizes that the mechanics behind SSc related DCLO changes probably are multifactorial and may involve pathology in the vasculature,” the study authors wrote. This was underscored by the observation that pulmonary hypertension (PH) was present in all groups of patients and supported the notion that PH screening should be conducted independently of fibrosis screening, the researchers noted.
For patients in the 1%-20% group, 146 were the same at follow-up, whereas the remaining patients progressed to more than 20% fibrosis. These 11 patients were characterized by significantly shorter average disease duration at baseline (1.3 years) compared with the other groups.
The 40 patients with more than 20% fibrosis at baseline had a higher annual fibrosis progression rate (aFPR), declining PFT values, and development of pulmonary hypertension (PH). Most of this group had diffuse SSc (55%), were positive for anti-topoisomerase antiboidies (ATA) (48%), and had a higher frequency of PH (28%), the researchers said. The rate of annual fibrosis progression differed across all groups and correlated with total FVC decline.
Surprisingly, neither baseline fibrosis nor annual fibrosis progression significantly predicted mortality. This finding may be partly due to survival bias in the cohort and the statistical power of the study, the researchers said. “The results indicate that a baseline examination in newly diagnosed SSc patients should include lung HRCT and PFTs,” the researchers concluded. Patients with low ILD risk should not undergo serial HCRT examination but probably need serial PFTs as an adjunct PH detection tool, they said.
Patients with newly diagnosed systemic sclerosis should have a high-resolution lung CT and pulmonary function tests, because when assessed together, their findings identify patients at high risk of interstitial lung disease, researchers say.
In a study of 305 patients with systemic sclerosis (SSc), a baseline high-resolution lung CT showing no fibrosis was highly predictive of a fibrosis free follow-up scan at 3 years, reported the researchers from Oslo (Norway) University Hospital. SSc associated interstitial lung–disease (SSc-ILD) typically has an insidious onset with subtle clinical symptoms, accoording to the authors in background information to the paper published in Arthritis & Rheumatology (Arthritis & Rheumatology 2015; [doi:10.1002/art.39166]).
This may explain why SSc-ILD is often diagnosed at an advanced stage, when extensive lung fibrosis is already present. “Better, and more targeted, strategies for SSc-ILD identification and risk stratification early in the disease course are therefore warranted,” they wrote.
In order to assess serial lung fibrosis measurements and paired pulmonary function tests (PFTs) as outcome prediction tools, the researchers prospectively analyzed both modalities at baseline and at an average of 3 years follow-up in 305 patients with SSc. The extent of fibrosis was scored on 10 sections from every high-resolution CT (HRCT) and expressed as a percentage of total lung volumes.
The researchers identified three groups of patients: More than 20% lung fibrosis (n=40), between 1%- 20% fibrosis (n=157), and no fibrosis (n=108). Results showed that all 108 patients who had no lung fibrosis at baseline remained free of fibrosis at a 3-year follow-up scan. These patients were predominantly female (88%) had limited (lc) SSc (84%), and were positive for anticentromere antibodies (ACA) (70%). They also had a high baseline decline in diffusing lung capacity for carbon monoxide (DLCO) that declined by 8.2%, the same degree as patients with lung fibrosis.
“This finding emphasizes that the mechanics behind SSc related DCLO changes probably are multifactorial and may involve pathology in the vasculature,” the study authors wrote. This was underscored by the observation that pulmonary hypertension (PH) was present in all groups of patients and supported the notion that PH screening should be conducted independently of fibrosis screening, the researchers noted.
For patients in the 1%-20% group, 146 were the same at follow-up, whereas the remaining patients progressed to more than 20% fibrosis. These 11 patients were characterized by significantly shorter average disease duration at baseline (1.3 years) compared with the other groups.
The 40 patients with more than 20% fibrosis at baseline had a higher annual fibrosis progression rate (aFPR), declining PFT values, and development of pulmonary hypertension (PH). Most of this group had diffuse SSc (55%), were positive for anti-topoisomerase antiboidies (ATA) (48%), and had a higher frequency of PH (28%), the researchers said. The rate of annual fibrosis progression differed across all groups and correlated with total FVC decline.
Surprisingly, neither baseline fibrosis nor annual fibrosis progression significantly predicted mortality. This finding may be partly due to survival bias in the cohort and the statistical power of the study, the researchers said. “The results indicate that a baseline examination in newly diagnosed SSc patients should include lung HRCT and PFTs,” the researchers concluded. Patients with low ILD risk should not undergo serial HCRT examination but probably need serial PFTs as an adjunct PH detection tool, they said.
Patients with newly diagnosed systemic sclerosis should have a high-resolution lung CT and pulmonary function tests, because when assessed together, their findings identify patients at high risk of interstitial lung disease, researchers say.
In a study of 305 patients with systemic sclerosis (SSc), a baseline high-resolution lung CT showing no fibrosis was highly predictive of a fibrosis free follow-up scan at 3 years, reported the researchers from Oslo (Norway) University Hospital. SSc associated interstitial lung–disease (SSc-ILD) typically has an insidious onset with subtle clinical symptoms, accoording to the authors in background information to the paper published in Arthritis & Rheumatology (Arthritis & Rheumatology 2015; [doi:10.1002/art.39166]).
This may explain why SSc-ILD is often diagnosed at an advanced stage, when extensive lung fibrosis is already present. “Better, and more targeted, strategies for SSc-ILD identification and risk stratification early in the disease course are therefore warranted,” they wrote.
In order to assess serial lung fibrosis measurements and paired pulmonary function tests (PFTs) as outcome prediction tools, the researchers prospectively analyzed both modalities at baseline and at an average of 3 years follow-up in 305 patients with SSc. The extent of fibrosis was scored on 10 sections from every high-resolution CT (HRCT) and expressed as a percentage of total lung volumes.
The researchers identified three groups of patients: More than 20% lung fibrosis (n=40), between 1%- 20% fibrosis (n=157), and no fibrosis (n=108). Results showed that all 108 patients who had no lung fibrosis at baseline remained free of fibrosis at a 3-year follow-up scan. These patients were predominantly female (88%) had limited (lc) SSc (84%), and were positive for anticentromere antibodies (ACA) (70%). They also had a high baseline decline in diffusing lung capacity for carbon monoxide (DLCO) that declined by 8.2%, the same degree as patients with lung fibrosis.
“This finding emphasizes that the mechanics behind SSc related DCLO changes probably are multifactorial and may involve pathology in the vasculature,” the study authors wrote. This was underscored by the observation that pulmonary hypertension (PH) was present in all groups of patients and supported the notion that PH screening should be conducted independently of fibrosis screening, the researchers noted.
For patients in the 1%-20% group, 146 were the same at follow-up, whereas the remaining patients progressed to more than 20% fibrosis. These 11 patients were characterized by significantly shorter average disease duration at baseline (1.3 years) compared with the other groups.
The 40 patients with more than 20% fibrosis at baseline had a higher annual fibrosis progression rate (aFPR), declining PFT values, and development of pulmonary hypertension (PH). Most of this group had diffuse SSc (55%), were positive for anti-topoisomerase antiboidies (ATA) (48%), and had a higher frequency of PH (28%), the researchers said. The rate of annual fibrosis progression differed across all groups and correlated with total FVC decline.
Surprisingly, neither baseline fibrosis nor annual fibrosis progression significantly predicted mortality. This finding may be partly due to survival bias in the cohort and the statistical power of the study, the researchers said. “The results indicate that a baseline examination in newly diagnosed SSc patients should include lung HRCT and PFTs,” the researchers concluded. Patients with low ILD risk should not undergo serial HCRT examination but probably need serial PFTs as an adjunct PH detection tool, they said.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Patients with newly diagnosed SSc should have baseline lung CT and pulmonary function tests
Major finding: Baseline high-resolution CT scans were highly predictive of fibrosis development and progression.
Data source: A prospective study of 305 consecutive SSc patients attending Oslo University Hospital.
Disclosures: No conflicts of interest were reported.
RA susceptibility gene linked with disease severity, treatment response
Specific haplotypes of the of the HLA-DRB1 gene – well known to confer increased risk for rheumatoid arthritis – proved to be strong, independent predictors of radiological disease severity, risk of death, and response to tumor necrosis factor inhibitor therapy in a three-cohort study involving more than 6,000 patients.
The report represents the first analysis to find significant predictors for those outcomes based on 16 haplotypes that are derived from three amino acid positions of the HLA-DRB1 gene. Two of those amino acid positions, 71 and 74, are within the classic shared epitope, which has been “associated with the development of anticitrullinated protein antibodies and has been consistently associated with markers of severe disease, such as radiological joint damage and mortality in patients with RA,” wrote Dr. Sebastien Viatte of the University of Manchester (England) and his coauthors (JAMA 2015;313:1645-56).
The third amino acid position examined in the study, position 11, which lies outside the shared epitope, was associated with increased risk for radiological damage, mortality, and response to tumor necrosis factor (TNF) inhibitor treatment, the latter of which neither position 71 or 74 was associated with.
To find these significant predictors of prognosis, the investigators examined the three amino acid positions in a large prospective cohort of patients with inflammatory polyarthritis or RA who were recruited at disease onset in the Norfolk Arthritis Register. They then independently validated the results for mortality and radiological damage in a replication cohort of patients from the Early Rheumatoid Arthritis Study study and for treatment response in patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort. All the patients were from the United Kingdom and had self-reported white ancestry.
Overall, radiographic outcome was associated with amino acid positions 11, 71, and 74 independently of each other and “completely superseded the shared epitope model.” Analyses of the effects of the three amino acid positions on all-cause mortality showed similar results. Change in the 28-joint Disease Activity Score or European League Against Rheumatism response was not associated with anticitrullinated protein antibodies or the shared epitope, but was significantly associated with valine at position 11.
Valine at position 11 consistently had the strongest effects on increasing risk for radiographic damage, mortality, and better TNF inhibitor treatment response. Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (odds ratio, 1.75; 95% confidence interval, 1.51-2.05) as measured by Larsen score. “Valine at [position 11] represents what we believe is the strongest single genetic association with radiographic damage identified to date,” they wrote.
Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16; 95% CI, 1.03-1.31; P = .01) and with better EULAR response to TNF inhibitor therapy (OR, 1.14; 95% CI, 1.01-1.30; P = .04).
The investigators found that the 16 haplotypes that existed in the cohorts based on the amino acid positions at 11, 71, and 74 of HLA-DRB1 could be used to construct a hierarchy of risk for the three outcome measures. For instance, they noted that the valine-containing VKA haplotype was associated with RA susceptibility (OR, 4.44; 95% CI, 4.02-4.91), joint erosions in patients with RA (OR, 1.82; 95% CI, 1.35-2.46), and a better response to TNF inhibitor drugs (OR, 1.23; 95% CI, 1.06-1.43). Although a 23% increase in the odds of good response to TNF inhibitors is “modest,” the researchers wrote, “it refers to the likelihood of moving from the EULAR [European League Against Rheumatism] category of none to a moderate response, or from a moderate to a good response for every copy of the VKA haplotype carried by the patient, compared with noncarriers.
“Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRBl haplotype analysis for management of RA,” the authors concluded.
The study was funded by a grant from Arthritis Research UK. Several authors reported receiving fees or grant support from companies that market drugs for RA.
Although the findings of Dr. Viatte and his colleagues do not have immediate clinical implications, identification of the precise HLA variants that influence disease course is of “great interest.”
The findings add to the ability to predict outcomes of RA, which could help optimize therapeutic strategies for different patients. They also shed light on the molecular mechanisms that determine disease course and mortality.
Dr. David T. Felson |
However, the increased risk of disease severity conferred by these HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74 has only a minor influence on disease outcomes in comparison to the larger explanatory power of environmental and lifestyle factors and also biomarkers. The best use of this data in predicting RA outcomes and optimizing treatment plans will be in updated prediction algorithms.
Dr. David T. Felson is with the clinical epidemiology research and training unit at Boston University and the National Institute for Health Research biomedical research unit at the University of Manchester (England). Dr. Lars Klareskog is with the rheumatology unit at Karolinska Institute in Stockholm. Their comments are taken from an editorial that accompanied Dr. Viatte and colleagues’ paper (JAMA 2015;313:1623-4). They reported having no conflicts of interest.
Although the findings of Dr. Viatte and his colleagues do not have immediate clinical implications, identification of the precise HLA variants that influence disease course is of “great interest.”
The findings add to the ability to predict outcomes of RA, which could help optimize therapeutic strategies for different patients. They also shed light on the molecular mechanisms that determine disease course and mortality.
Dr. David T. Felson |
However, the increased risk of disease severity conferred by these HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74 has only a minor influence on disease outcomes in comparison to the larger explanatory power of environmental and lifestyle factors and also biomarkers. The best use of this data in predicting RA outcomes and optimizing treatment plans will be in updated prediction algorithms.
Dr. David T. Felson is with the clinical epidemiology research and training unit at Boston University and the National Institute for Health Research biomedical research unit at the University of Manchester (England). Dr. Lars Klareskog is with the rheumatology unit at Karolinska Institute in Stockholm. Their comments are taken from an editorial that accompanied Dr. Viatte and colleagues’ paper (JAMA 2015;313:1623-4). They reported having no conflicts of interest.
Although the findings of Dr. Viatte and his colleagues do not have immediate clinical implications, identification of the precise HLA variants that influence disease course is of “great interest.”
The findings add to the ability to predict outcomes of RA, which could help optimize therapeutic strategies for different patients. They also shed light on the molecular mechanisms that determine disease course and mortality.
Dr. David T. Felson |
However, the increased risk of disease severity conferred by these HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74 has only a minor influence on disease outcomes in comparison to the larger explanatory power of environmental and lifestyle factors and also biomarkers. The best use of this data in predicting RA outcomes and optimizing treatment plans will be in updated prediction algorithms.
Dr. David T. Felson is with the clinical epidemiology research and training unit at Boston University and the National Institute for Health Research biomedical research unit at the University of Manchester (England). Dr. Lars Klareskog is with the rheumatology unit at Karolinska Institute in Stockholm. Their comments are taken from an editorial that accompanied Dr. Viatte and colleagues’ paper (JAMA 2015;313:1623-4). They reported having no conflicts of interest.
Specific haplotypes of the of the HLA-DRB1 gene – well known to confer increased risk for rheumatoid arthritis – proved to be strong, independent predictors of radiological disease severity, risk of death, and response to tumor necrosis factor inhibitor therapy in a three-cohort study involving more than 6,000 patients.
The report represents the first analysis to find significant predictors for those outcomes based on 16 haplotypes that are derived from three amino acid positions of the HLA-DRB1 gene. Two of those amino acid positions, 71 and 74, are within the classic shared epitope, which has been “associated with the development of anticitrullinated protein antibodies and has been consistently associated with markers of severe disease, such as radiological joint damage and mortality in patients with RA,” wrote Dr. Sebastien Viatte of the University of Manchester (England) and his coauthors (JAMA 2015;313:1645-56).
The third amino acid position examined in the study, position 11, which lies outside the shared epitope, was associated with increased risk for radiological damage, mortality, and response to tumor necrosis factor (TNF) inhibitor treatment, the latter of which neither position 71 or 74 was associated with.
To find these significant predictors of prognosis, the investigators examined the three amino acid positions in a large prospective cohort of patients with inflammatory polyarthritis or RA who were recruited at disease onset in the Norfolk Arthritis Register. They then independently validated the results for mortality and radiological damage in a replication cohort of patients from the Early Rheumatoid Arthritis Study study and for treatment response in patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort. All the patients were from the United Kingdom and had self-reported white ancestry.
Overall, radiographic outcome was associated with amino acid positions 11, 71, and 74 independently of each other and “completely superseded the shared epitope model.” Analyses of the effects of the three amino acid positions on all-cause mortality showed similar results. Change in the 28-joint Disease Activity Score or European League Against Rheumatism response was not associated with anticitrullinated protein antibodies or the shared epitope, but was significantly associated with valine at position 11.
Valine at position 11 consistently had the strongest effects on increasing risk for radiographic damage, mortality, and better TNF inhibitor treatment response. Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (odds ratio, 1.75; 95% confidence interval, 1.51-2.05) as measured by Larsen score. “Valine at [position 11] represents what we believe is the strongest single genetic association with radiographic damage identified to date,” they wrote.
Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16; 95% CI, 1.03-1.31; P = .01) and with better EULAR response to TNF inhibitor therapy (OR, 1.14; 95% CI, 1.01-1.30; P = .04).
The investigators found that the 16 haplotypes that existed in the cohorts based on the amino acid positions at 11, 71, and 74 of HLA-DRB1 could be used to construct a hierarchy of risk for the three outcome measures. For instance, they noted that the valine-containing VKA haplotype was associated with RA susceptibility (OR, 4.44; 95% CI, 4.02-4.91), joint erosions in patients with RA (OR, 1.82; 95% CI, 1.35-2.46), and a better response to TNF inhibitor drugs (OR, 1.23; 95% CI, 1.06-1.43). Although a 23% increase in the odds of good response to TNF inhibitors is “modest,” the researchers wrote, “it refers to the likelihood of moving from the EULAR [European League Against Rheumatism] category of none to a moderate response, or from a moderate to a good response for every copy of the VKA haplotype carried by the patient, compared with noncarriers.
“Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRBl haplotype analysis for management of RA,” the authors concluded.
The study was funded by a grant from Arthritis Research UK. Several authors reported receiving fees or grant support from companies that market drugs for RA.
Specific haplotypes of the of the HLA-DRB1 gene – well known to confer increased risk for rheumatoid arthritis – proved to be strong, independent predictors of radiological disease severity, risk of death, and response to tumor necrosis factor inhibitor therapy in a three-cohort study involving more than 6,000 patients.
The report represents the first analysis to find significant predictors for those outcomes based on 16 haplotypes that are derived from three amino acid positions of the HLA-DRB1 gene. Two of those amino acid positions, 71 and 74, are within the classic shared epitope, which has been “associated with the development of anticitrullinated protein antibodies and has been consistently associated with markers of severe disease, such as radiological joint damage and mortality in patients with RA,” wrote Dr. Sebastien Viatte of the University of Manchester (England) and his coauthors (JAMA 2015;313:1645-56).
The third amino acid position examined in the study, position 11, which lies outside the shared epitope, was associated with increased risk for radiological damage, mortality, and response to tumor necrosis factor (TNF) inhibitor treatment, the latter of which neither position 71 or 74 was associated with.
To find these significant predictors of prognosis, the investigators examined the three amino acid positions in a large prospective cohort of patients with inflammatory polyarthritis or RA who were recruited at disease onset in the Norfolk Arthritis Register. They then independently validated the results for mortality and radiological damage in a replication cohort of patients from the Early Rheumatoid Arthritis Study study and for treatment response in patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort. All the patients were from the United Kingdom and had self-reported white ancestry.
Overall, radiographic outcome was associated with amino acid positions 11, 71, and 74 independently of each other and “completely superseded the shared epitope model.” Analyses of the effects of the three amino acid positions on all-cause mortality showed similar results. Change in the 28-joint Disease Activity Score or European League Against Rheumatism response was not associated with anticitrullinated protein antibodies or the shared epitope, but was significantly associated with valine at position 11.
Valine at position 11 consistently had the strongest effects on increasing risk for radiographic damage, mortality, and better TNF inhibitor treatment response. Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (odds ratio, 1.75; 95% confidence interval, 1.51-2.05) as measured by Larsen score. “Valine at [position 11] represents what we believe is the strongest single genetic association with radiographic damage identified to date,” they wrote.
Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16; 95% CI, 1.03-1.31; P = .01) and with better EULAR response to TNF inhibitor therapy (OR, 1.14; 95% CI, 1.01-1.30; P = .04).
The investigators found that the 16 haplotypes that existed in the cohorts based on the amino acid positions at 11, 71, and 74 of HLA-DRB1 could be used to construct a hierarchy of risk for the three outcome measures. For instance, they noted that the valine-containing VKA haplotype was associated with RA susceptibility (OR, 4.44; 95% CI, 4.02-4.91), joint erosions in patients with RA (OR, 1.82; 95% CI, 1.35-2.46), and a better response to TNF inhibitor drugs (OR, 1.23; 95% CI, 1.06-1.43). Although a 23% increase in the odds of good response to TNF inhibitors is “modest,” the researchers wrote, “it refers to the likelihood of moving from the EULAR [European League Against Rheumatism] category of none to a moderate response, or from a moderate to a good response for every copy of the VKA haplotype carried by the patient, compared with noncarriers.
“Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRBl haplotype analysis for management of RA,” the authors concluded.
The study was funded by a grant from Arthritis Research UK. Several authors reported receiving fees or grant support from companies that market drugs for RA.
FROM JAMA
Key clinical finding: The HLA-DRB1 haplotype status of patients with RA may affect radiological damage, mortality, and response to anti-TNF agents.
Major finding: Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (odds ratio, 1.75; 95% confidence interval, 1.51-2.05) as measured by Larsen score.
Data source: More than 6,000 RA patients from the Norfolk Arthritis Registry, Early Rheumatoid Arthritis Study, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort.
Disclosures: The study was funded by a grant from Arthritis Research UK. Several authors reported receiving fees or grant support from companies that market drugs for RA.
Etanercept maintenance therapy feasible in some RA patients
Rheumatoid arthritis patients with low disease activity are less likely to flare if they continue their treatment with etanercept and methotrexate, even if they take half the dose of the anti-TNF agent, a double-blind, randomized trial showed.
The researchers conducting the trial, called DOSERA (Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State), led by Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm, reported that the proportion of patients who successfully maintained low disease activity was significantly higher with etanercept 50 mg (52%; P = .007) and 25 mg (44%; P = .044), compared with placebo (13%). They defined failure as an increase in 28-joint Disease Activity Score (DAS28) of 0.6 or more and an absolute value of greater than 3.2 or disease progression as determined by investigator/patient assessment.
According to the authors, the results are important because, theoretically, they represent the first controlled demonstration that an induction maintenance strategy can be applied in some patients with established RA for whom the use of an anti-TNF agent is clinically necessary.
From a clinical practice point of view, the results also suggest that it might be possible to reduce dosages in some patients while maintaining the same favorable disease state.
“However, a full assessment of this possibility would require considerably more robust data in a larger population on the full clinical as well as radiographic effects, both short term and long term,” Dr. van Vollenhoven and his associates wrote, adding that “it is not possible to know whether these data would apply equally to other anti-TNF agents.”
Median time to flare was significantly shorter for patients taking methotrexate plus placebo at 6 weeks, compared with etanercept 50 mg at 48 weeks (P = .001) and 25 mg at 36 weeks (P < .001), the researchers reported (Ann. Rheum. Dis. 2015 April 14 [doi:10.1136/annrheumdis-2014-205726]).
Most patients (91%) who flared and then restarted open-label etanercept 50 mg/week responded promptly, with median times until low disease activity or remission being 6.0 weeks for the 50-mg group, 5.9 weeks for the 25-mg group, and 3.9 weeks for the placebo group.
Adverse events were consistent with the patient population and known side effects of etanercept and methotrexate.
The study had several weaknesses, including its limited size and associated wide confidence intervals, the researchers noted, resulting in “uncertainty regarding the comparison of the clinical efficacies of full-dose and reduced-dose [etanercept] continuation.”
Etanercept also is not approved at doses other than 50 mg for the treatment of adults with RA. A dose reduction was therefore not supported by the product label and also entails some practical difficulties, Dr. van Vollenhoven and his associates added.
The study included 91 patients who had been receiving etanercept, 50 mg/week, plus methotrexate, 7.5-25 mg/week for at least 14 months and had a DAS28 score of 3.2 or lower.
After an 8-week run-in phase, 73 patients were randomized in a double-blind design to etanercept 50 mg/week plus methotrexate, etanercept 25 mg/week plus methotrexate, or placebo plus methotrexate for 48 weeks.
The study was sponsored by Wyeth, which was acquired by Pfizer. The investigators designed the study protocol prior to the agreement by Wyeth to support the study. Some of the authors reported receiving research support and/or honoraria from numerous pharmaceutical companies or serving as consultants to them. Several reported being employees of Wyeth or Pfizer at the time of the study.
Rheumatoid arthritis patients with low disease activity are less likely to flare if they continue their treatment with etanercept and methotrexate, even if they take half the dose of the anti-TNF agent, a double-blind, randomized trial showed.
The researchers conducting the trial, called DOSERA (Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State), led by Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm, reported that the proportion of patients who successfully maintained low disease activity was significantly higher with etanercept 50 mg (52%; P = .007) and 25 mg (44%; P = .044), compared with placebo (13%). They defined failure as an increase in 28-joint Disease Activity Score (DAS28) of 0.6 or more and an absolute value of greater than 3.2 or disease progression as determined by investigator/patient assessment.
According to the authors, the results are important because, theoretically, they represent the first controlled demonstration that an induction maintenance strategy can be applied in some patients with established RA for whom the use of an anti-TNF agent is clinically necessary.
From a clinical practice point of view, the results also suggest that it might be possible to reduce dosages in some patients while maintaining the same favorable disease state.
“However, a full assessment of this possibility would require considerably more robust data in a larger population on the full clinical as well as radiographic effects, both short term and long term,” Dr. van Vollenhoven and his associates wrote, adding that “it is not possible to know whether these data would apply equally to other anti-TNF agents.”
Median time to flare was significantly shorter for patients taking methotrexate plus placebo at 6 weeks, compared with etanercept 50 mg at 48 weeks (P = .001) and 25 mg at 36 weeks (P < .001), the researchers reported (Ann. Rheum. Dis. 2015 April 14 [doi:10.1136/annrheumdis-2014-205726]).
Most patients (91%) who flared and then restarted open-label etanercept 50 mg/week responded promptly, with median times until low disease activity or remission being 6.0 weeks for the 50-mg group, 5.9 weeks for the 25-mg group, and 3.9 weeks for the placebo group.
Adverse events were consistent with the patient population and known side effects of etanercept and methotrexate.
The study had several weaknesses, including its limited size and associated wide confidence intervals, the researchers noted, resulting in “uncertainty regarding the comparison of the clinical efficacies of full-dose and reduced-dose [etanercept] continuation.”
Etanercept also is not approved at doses other than 50 mg for the treatment of adults with RA. A dose reduction was therefore not supported by the product label and also entails some practical difficulties, Dr. van Vollenhoven and his associates added.
The study included 91 patients who had been receiving etanercept, 50 mg/week, plus methotrexate, 7.5-25 mg/week for at least 14 months and had a DAS28 score of 3.2 or lower.
After an 8-week run-in phase, 73 patients were randomized in a double-blind design to etanercept 50 mg/week plus methotrexate, etanercept 25 mg/week plus methotrexate, or placebo plus methotrexate for 48 weeks.
The study was sponsored by Wyeth, which was acquired by Pfizer. The investigators designed the study protocol prior to the agreement by Wyeth to support the study. Some of the authors reported receiving research support and/or honoraria from numerous pharmaceutical companies or serving as consultants to them. Several reported being employees of Wyeth or Pfizer at the time of the study.
Rheumatoid arthritis patients with low disease activity are less likely to flare if they continue their treatment with etanercept and methotrexate, even if they take half the dose of the anti-TNF agent, a double-blind, randomized trial showed.
The researchers conducting the trial, called DOSERA (Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State), led by Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm, reported that the proportion of patients who successfully maintained low disease activity was significantly higher with etanercept 50 mg (52%; P = .007) and 25 mg (44%; P = .044), compared with placebo (13%). They defined failure as an increase in 28-joint Disease Activity Score (DAS28) of 0.6 or more and an absolute value of greater than 3.2 or disease progression as determined by investigator/patient assessment.
According to the authors, the results are important because, theoretically, they represent the first controlled demonstration that an induction maintenance strategy can be applied in some patients with established RA for whom the use of an anti-TNF agent is clinically necessary.
From a clinical practice point of view, the results also suggest that it might be possible to reduce dosages in some patients while maintaining the same favorable disease state.
“However, a full assessment of this possibility would require considerably more robust data in a larger population on the full clinical as well as radiographic effects, both short term and long term,” Dr. van Vollenhoven and his associates wrote, adding that “it is not possible to know whether these data would apply equally to other anti-TNF agents.”
Median time to flare was significantly shorter for patients taking methotrexate plus placebo at 6 weeks, compared with etanercept 50 mg at 48 weeks (P = .001) and 25 mg at 36 weeks (P < .001), the researchers reported (Ann. Rheum. Dis. 2015 April 14 [doi:10.1136/annrheumdis-2014-205726]).
Most patients (91%) who flared and then restarted open-label etanercept 50 mg/week responded promptly, with median times until low disease activity or remission being 6.0 weeks for the 50-mg group, 5.9 weeks for the 25-mg group, and 3.9 weeks for the placebo group.
Adverse events were consistent with the patient population and known side effects of etanercept and methotrexate.
The study had several weaknesses, including its limited size and associated wide confidence intervals, the researchers noted, resulting in “uncertainty regarding the comparison of the clinical efficacies of full-dose and reduced-dose [etanercept] continuation.”
Etanercept also is not approved at doses other than 50 mg for the treatment of adults with RA. A dose reduction was therefore not supported by the product label and also entails some practical difficulties, Dr. van Vollenhoven and his associates added.
The study included 91 patients who had been receiving etanercept, 50 mg/week, plus methotrexate, 7.5-25 mg/week for at least 14 months and had a DAS28 score of 3.2 or lower.
After an 8-week run-in phase, 73 patients were randomized in a double-blind design to etanercept 50 mg/week plus methotrexate, etanercept 25 mg/week plus methotrexate, or placebo plus methotrexate for 48 weeks.
The study was sponsored by Wyeth, which was acquired by Pfizer. The investigators designed the study protocol prior to the agreement by Wyeth to support the study. Some of the authors reported receiving research support and/or honoraria from numerous pharmaceutical companies or serving as consultants to them. Several reported being employees of Wyeth or Pfizer at the time of the study.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: An induction maintenance strategy with etanercept can be applied in some patients with established RA for whom the use of an anti-TNF agent is clinically necessary.
Major Finding: The proportion of patients who successfully maintained low disease activity was significantly higher with etanercept 50 mg (52%; P = .007) and 25 mg (44%; P = .044), compared with placebo (13%).
Data Source: A double-blind, randomized study of 73 RA patients with low disease activity.
Disclosures: The study was sponsored by Wyeth, which was acquired by Pfizer. The investigators designed the study protocol prior to the agreement by Wyeth to support the study. Some of the authors reported receiving research support and/or honoraria from numerous pharmaceutical companies or serving as consultants to them. Several reported being employees of Wyeth or Pfizer at the time of the study.
Overall physical health strongly predicts arthritis pain
Physical health, previous joint pain, and the presence of diabetes can strongly predict whether a patient with arthritis will experience pain, say researchers presenting their findings at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.
Man Hung, Ph.D., of the department of orthopaedic surgery operations at the University of Utah in Salt Lake City and her colleagues created several algorithms for predicting arthritis pain based on data from a sample of 5,721 U.S. adults with arthritis with an average age of 60 years.
They discovered that specific combinations of physical health, mental health, and general health status, as well as diabetes, previous joint pain, and a patient’s education level, predicted pain in people with arthritis.
Physical health status the greatest predictor of pain that limited work, whereas a body mass index greater than 30 kg/m2 was not linked to pain, the researchers found.
One of the algorithms that the researchers developed was able to predict pain at an accuracy rate of 98.6%, they said
The algorithms offer new insights of pain, allowing the development of cost-effective care management programs for those experiencing arthritis, they concluded.
Physical health, previous joint pain, and the presence of diabetes can strongly predict whether a patient with arthritis will experience pain, say researchers presenting their findings at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.
Man Hung, Ph.D., of the department of orthopaedic surgery operations at the University of Utah in Salt Lake City and her colleagues created several algorithms for predicting arthritis pain based on data from a sample of 5,721 U.S. adults with arthritis with an average age of 60 years.
They discovered that specific combinations of physical health, mental health, and general health status, as well as diabetes, previous joint pain, and a patient’s education level, predicted pain in people with arthritis.
Physical health status the greatest predictor of pain that limited work, whereas a body mass index greater than 30 kg/m2 was not linked to pain, the researchers found.
One of the algorithms that the researchers developed was able to predict pain at an accuracy rate of 98.6%, they said
The algorithms offer new insights of pain, allowing the development of cost-effective care management programs for those experiencing arthritis, they concluded.
Physical health, previous joint pain, and the presence of diabetes can strongly predict whether a patient with arthritis will experience pain, say researchers presenting their findings at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.
Man Hung, Ph.D., of the department of orthopaedic surgery operations at the University of Utah in Salt Lake City and her colleagues created several algorithms for predicting arthritis pain based on data from a sample of 5,721 U.S. adults with arthritis with an average age of 60 years.
They discovered that specific combinations of physical health, mental health, and general health status, as well as diabetes, previous joint pain, and a patient’s education level, predicted pain in people with arthritis.
Physical health status the greatest predictor of pain that limited work, whereas a body mass index greater than 30 kg/m2 was not linked to pain, the researchers found.
One of the algorithms that the researchers developed was able to predict pain at an accuracy rate of 98.6%, they said
The algorithms offer new insights of pain, allowing the development of cost-effective care management programs for those experiencing arthritis, they concluded.
Treat-to-target approach for RA has cardiovascular benefits
Rheumatoid arthritis patients have a significantly reduced risk of cardiovascular events if their disease is under control, based on an analysis of data from the CORRONA registry.
Investigators led by Dr. Daniel H. Solomon from Brigham and Women’s Hospital in Boston used longitudinal data from almost 25,000 RA patients who were tracked for a median of 2.7 years to find a 21% reduction (95% confidence interval, 13%-29%) in the risk of a composite outcome of the first confirmed myocardial infarction, stroke, or CV death event for each 10-point decline in the Clinical Disease Activity Index and a 53% reduction (95% confidence interval, 30%-68%) from high disease activity to remission.
“These results add significant new information regarding the importance of sustained control of RA disease activity, not only for improvement in pain and function, but also for reduced CV risk,” the authors wrote (Arthritis Rheumatol. 2015 [doi:10.1002/art.39098]).
The findings held true even after researchers adjusted for the use of immunomodulatory treatment, suggesting that controlling disease activity may be a more important management strategy than use of an immunomodulator, at least in the context of preventing CV events, they said.
“This is a hypothesis worth testing especially as enthusiasm grows for use of combination synthetic DMARDs [disease-modifying antirheumatic drugs],” they wrote.
Another clinical implication of the findings was that the adoption of a treat-to-target strategy in RA might be beneficial not only because of the observed improvement in pain and function but also because of a reduction in CV risk, they said.
“While these findings should not be interpreted to mean that traditional risk factors are not important, they do support the current RA recommendations for treating to low disease activity or remission,” they added.
In an accompanying editorial, Dr. Michael T. Nurmohamed of the department of rheumatology at VU University, Amsterdam, agreed with the authors that controlling disease activity (from a CV point of view) counted more than the drug used to achieve the low disease activity state or remission (Arthritis Rheumatol. 2015 [doi:10.1002/art.39096]).
“As inflammation plays a pivotal role in atherosclerotic disease it is not surprising that antirheumatic drugs such as methotrexate, the IL-1 inhibitor canakinumab and the IL-6 inhibitor tocilizumab are presently investigated in several trials as secondary prevention for recurrent CV events in ‘general population’ patients,” he said.
Although the current state-of-art treatment goals for patients with RA appear also to improve the CV risk of patients, it is important to realize there is still no evidence from randomized trials that RA treatment itself reduces CV risk. And despite the fact that rheumatologists know that traditional CV risk factors are important in RA, the management of CV risk factors in daily clinical practice are still poor, he said.
“Another challenge for the next years is to fulfill this unmet need for effective CV risk management implementation strategies,” he concluded.
The researchers declared receiving financial support from various pharmaceutical companies, but none were specifically linked to the current study. The study was supported by CORRONA, which has received subscription fees from a variety of pharmaceutical companies in the past 2 years, but none relating specifically to this study.
Rheumatoid arthritis patients have a significantly reduced risk of cardiovascular events if their disease is under control, based on an analysis of data from the CORRONA registry.
Investigators led by Dr. Daniel H. Solomon from Brigham and Women’s Hospital in Boston used longitudinal data from almost 25,000 RA patients who were tracked for a median of 2.7 years to find a 21% reduction (95% confidence interval, 13%-29%) in the risk of a composite outcome of the first confirmed myocardial infarction, stroke, or CV death event for each 10-point decline in the Clinical Disease Activity Index and a 53% reduction (95% confidence interval, 30%-68%) from high disease activity to remission.
“These results add significant new information regarding the importance of sustained control of RA disease activity, not only for improvement in pain and function, but also for reduced CV risk,” the authors wrote (Arthritis Rheumatol. 2015 [doi:10.1002/art.39098]).
The findings held true even after researchers adjusted for the use of immunomodulatory treatment, suggesting that controlling disease activity may be a more important management strategy than use of an immunomodulator, at least in the context of preventing CV events, they said.
“This is a hypothesis worth testing especially as enthusiasm grows for use of combination synthetic DMARDs [disease-modifying antirheumatic drugs],” they wrote.
Another clinical implication of the findings was that the adoption of a treat-to-target strategy in RA might be beneficial not only because of the observed improvement in pain and function but also because of a reduction in CV risk, they said.
“While these findings should not be interpreted to mean that traditional risk factors are not important, they do support the current RA recommendations for treating to low disease activity or remission,” they added.
In an accompanying editorial, Dr. Michael T. Nurmohamed of the department of rheumatology at VU University, Amsterdam, agreed with the authors that controlling disease activity (from a CV point of view) counted more than the drug used to achieve the low disease activity state or remission (Arthritis Rheumatol. 2015 [doi:10.1002/art.39096]).
“As inflammation plays a pivotal role in atherosclerotic disease it is not surprising that antirheumatic drugs such as methotrexate, the IL-1 inhibitor canakinumab and the IL-6 inhibitor tocilizumab are presently investigated in several trials as secondary prevention for recurrent CV events in ‘general population’ patients,” he said.
Although the current state-of-art treatment goals for patients with RA appear also to improve the CV risk of patients, it is important to realize there is still no evidence from randomized trials that RA treatment itself reduces CV risk. And despite the fact that rheumatologists know that traditional CV risk factors are important in RA, the management of CV risk factors in daily clinical practice are still poor, he said.
“Another challenge for the next years is to fulfill this unmet need for effective CV risk management implementation strategies,” he concluded.
The researchers declared receiving financial support from various pharmaceutical companies, but none were specifically linked to the current study. The study was supported by CORRONA, which has received subscription fees from a variety of pharmaceutical companies in the past 2 years, but none relating specifically to this study.
Rheumatoid arthritis patients have a significantly reduced risk of cardiovascular events if their disease is under control, based on an analysis of data from the CORRONA registry.
Investigators led by Dr. Daniel H. Solomon from Brigham and Women’s Hospital in Boston used longitudinal data from almost 25,000 RA patients who were tracked for a median of 2.7 years to find a 21% reduction (95% confidence interval, 13%-29%) in the risk of a composite outcome of the first confirmed myocardial infarction, stroke, or CV death event for each 10-point decline in the Clinical Disease Activity Index and a 53% reduction (95% confidence interval, 30%-68%) from high disease activity to remission.
“These results add significant new information regarding the importance of sustained control of RA disease activity, not only for improvement in pain and function, but also for reduced CV risk,” the authors wrote (Arthritis Rheumatol. 2015 [doi:10.1002/art.39098]).
The findings held true even after researchers adjusted for the use of immunomodulatory treatment, suggesting that controlling disease activity may be a more important management strategy than use of an immunomodulator, at least in the context of preventing CV events, they said.
“This is a hypothesis worth testing especially as enthusiasm grows for use of combination synthetic DMARDs [disease-modifying antirheumatic drugs],” they wrote.
Another clinical implication of the findings was that the adoption of a treat-to-target strategy in RA might be beneficial not only because of the observed improvement in pain and function but also because of a reduction in CV risk, they said.
“While these findings should not be interpreted to mean that traditional risk factors are not important, they do support the current RA recommendations for treating to low disease activity or remission,” they added.
In an accompanying editorial, Dr. Michael T. Nurmohamed of the department of rheumatology at VU University, Amsterdam, agreed with the authors that controlling disease activity (from a CV point of view) counted more than the drug used to achieve the low disease activity state or remission (Arthritis Rheumatol. 2015 [doi:10.1002/art.39096]).
“As inflammation plays a pivotal role in atherosclerotic disease it is not surprising that antirheumatic drugs such as methotrexate, the IL-1 inhibitor canakinumab and the IL-6 inhibitor tocilizumab are presently investigated in several trials as secondary prevention for recurrent CV events in ‘general population’ patients,” he said.
Although the current state-of-art treatment goals for patients with RA appear also to improve the CV risk of patients, it is important to realize there is still no evidence from randomized trials that RA treatment itself reduces CV risk. And despite the fact that rheumatologists know that traditional CV risk factors are important in RA, the management of CV risk factors in daily clinical practice are still poor, he said.
“Another challenge for the next years is to fulfill this unmet need for effective CV risk management implementation strategies,” he concluded.
The researchers declared receiving financial support from various pharmaceutical companies, but none were specifically linked to the current study. The study was supported by CORRONA, which has received subscription fees from a variety of pharmaceutical companies in the past 2 years, but none relating specifically to this study.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: In a large cohort of RA patients, a clear dose-response effect was observed with reductions in disease activity associated with reduced CV risk, independent of immunomodulatory treatments.
Major finding: RA patients had a 21% reduction in the risk of a composite outcome of the first confirmed myocardial infarction, stroke, or CV death event for each 10-point decline in the Clinical Disease Activity Index and a 53% reduction from high disease activity to remission.
Data source: 24,989 patients with RA who were part of the ongoing CORRONA patient registry and were followed for a median of 2.7 years.
Disclosures: The researchers declared receiving financial support from various pharmaceutical companies, but none were specifically linked to the current study. The study was supported by CORRONA, which has received subscription fees from a variety of pharmaceutical companies in the past 2 years, but none relating specifically to this study.
Study addresses outcomes of nonsevere ANCA-associated vasculitis relapses for first time
Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: ANCA-positive patients with severe disease who experience a nonsevere relapse after remission may require immunosuppressive therapy beyond steroids.
Major finding: A total of 70% of patients who experienced a first nonsevere relapse but went into remission following an increase in their prednisone dose still had a second severe or nonsevere relapse within an average of 6 months.
Data source: A total of 44 patients from the RAVE trial who had nonsevere relapse during months 1-18 of the study.
Disclosures: The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
Physician Agreement to ‘Spread Out’ Childhood Vaccines Growing
The number of clinicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
The number of clinicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
The number of clinicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
FROM PEDIATRICS
Physician agreement to ‘spread out’ childhood vaccines growing
The number of physicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
Practice good scientific medicine
Dr. Barbara Pahud is assistant professor of pediatrics at the University of
Missouri, Kansas City. She said that she had no relevant financial disclosures.
Practice good scientific medicine
Dr. Barbara Pahud is assistant professor of pediatrics at the University of
Missouri, Kansas City. She said that she had no relevant financial disclosures.
Practice good scientific medicine
Dr. Barbara Pahud is assistant professor of pediatrics at the University of
Missouri, Kansas City. She said that she had no relevant financial disclosures.
The number of physicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
The number of physicians agreeing to parental requests to spread out vaccines tripled between 2009 and 2012 despite safety concerns, a survey shows.
Writing in Pediatrics, the authors said some parents were requesting delays to their child’s vaccination schedules, believing it was safer (Pediatrics 2015 [doi: 10.1542/peds.2014-3474]).
It was unknown how these requests were being handled by pediatric and primary care physicians said Dr Allison Kempe from the Children’s Hospital Colorado in Aurora, and her associates.
The survey mailed to 534 pediatricians and family physicians found that in a typical month 93% received parental requests to spread out vaccines. Results showed that 37% “often or always” agreed to the request and 37% “sometimes” agreed. This was in stark contrast to a similar survey conducted in 2009 that showed 13% “often or always” agreed to the request.
“This shift may reflect changes in the beliefs of physicians about what is effective in working with hesitant parents, adherence to published recommendations about how to build trust with vaccine hesitant parents, or simply a pragmatic reaction to the amount of time it takes to discuss parents’ concerns in the context of a busy practice setting,” the study authors wrote.
The rise in granting requests to delay vaccines was despite 87% of respondents saying they thought parents were putting their children at risk of disease.
The reasons physicians gave for agreeing to requests included building trust with families (82%) and fear that families might leave their practice (80%) if they declined the request.
Dealing with parental requests was time consuming, the survey showed, with roughly half of physicians saying they spent more than 10 minutes in discussions with parents who had vaccine concerns.
This could equate to more than half of a well-child visit, shortchanging other important areas of child development, the authors said.
Physicians reported using many strategies in response to requests to deviate from vaccine schedules but most had a “relatively bleak” perception of their effectiveness, the researchers said.
“Our study points out the need for an evidence base to guide primary care physicians in efforts to increase timely vaccination,” they concluded.
Conversations around vaccinations needed to start early in pregnancy “because [recent data suggests] that is when vaccine decision-making begins, especially for parents who are hesitant about vaccines,” they added. Also, “amplifying the voice of the vast majority of parents who do follow vaccination recommendations in public messaging and in settings such as preschools and schools could be a powerful tool .”
The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: Most physicians are asked to spread out childhood vaccines, and more than a third agree to do so.
Major finding: Results showed that 37% “often or always” agreed to the request, compared with 13% in 2009.
Data source: A survey mailed to 534 pediatricians and family physicians.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. The authors had no relevant financial disclosures.
Study: Osteoarthritis develops sooner than thought after ACL injury, repair
People who have had a knee reconstruction following trauma may be susceptible to osteoarthritis sooner than currently thought, according to new MRI findings at 1 year after anterior cruciate ligament reconstruction.
Almost a third of people studied had some evidence of early osteoarthritis (OA) at that early time point, challenging “existing dogma that degenerative joint disease does not become apparent for years post-ACLR,” reported Dr. Kay Crossley of the University of Queensland in Brisbane, Australia (Arthritis Rheumatol. 2015 Feb. 18 [doi:10.1002/art.39005]).
However, as they did not have access to preoperative images, they could not rule out that some OA features may have been preexisting and not related to knee trauma, they said.
“This is a sample that was taken after the injury and after the reconstruction, so they truly don’t know that what they’re finding is as a result of even the injury, surgery, or the meniscal damage or meniscal resection they had done at the time,” Dr. David J. Hunter, a leading OA expert from Sydney (Australia) University, said when asked to comment on the study’s findings.
“It may well be that these were people that had some underlying structural damage,” he added.
The researchers noted that radiographic knee OA was thought to be as high as 50%-90% a decade after anterior cruciate ligament reconstruction (ACLR). The issue is particularly important because ACL injuries typically occur in younger adults who are then prone to developing knee OA before they reach 40 years, they said.
“Early detection of knee OA after ACLR may permit early intervention such as load management, which is likely to be more effective prior to the development of advanced disease,” they wrote.
Their study included 111 patients aged 18-50 years who had undergone single-bundle hamstring-tendon autograft ACLR 1 year earlier.
MRI scans of their knees were compared with 20 uninjured asymptomatic matched controls. The researchers used the MRI Osteoarthritis Knee Score (MOAKS) to score specific OA features because the more recent Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) had not been published at the time of their study.
Results showed that 34 (31%) patients had MRI-defined knee OA following an ACLR a year earlier.
MRI-OA features were most frequently found in the patellofemoral compartment, particularly the medial femoral trochlea, a potentially underrecognized site of knee pathology following reconstruction, the researchers said.
Pathology in the patellofemoral joint included not only “early” features of OA, such as bone marrow lesions and partial-thickness cartilage loss, but also frank osteophytes on MRI, they noted.
None of the uninjured control knees had MRI-defined patellofemoral or tibiofemoral OA.
The authors acknowledged that a lack of access to preoperative knee images limited the conclusions they could reach in their study, but they noted that MRI-OA features were rarely seen in the small sample of uninjured matched control knees.
“Combined with the observation that six times as many reconstructed knees had radiographic osteophytes than uninjured contralateral knees, these findings suggest that knee trauma and/or reconstruction was strongly implicated in the development of OA features,” they wrote.
Another limitation that the authors acknowledged was that the MRI definition of OA was relatively new and was likely to be refined as the understanding of OA pathology evolved.
Dr. Hunter, who was the lead investigator involved in developing the MOAKS, agreed that the definition needed more validity and testing.
“This is the third study that uses that definition, and I do think that long-term clinical implications of what MRI definition means is unknown,” he said. “The challenge that we have is that we do kick up a lot of abnormalities, and we don’t truly know what the long-term clinical implications of those abnormalities are at this point.”
“There are a lot of problems with the way this study has been done, but I do think it is really helpful that it highlights how important injury is with regards to predisposing to early OA.”
“It’s something that a lot of people don’t really highlight or pay attention to,” he said.
The study was partly funded by the Queensland Orthopaedic Physiotherapy Network, a University of Melbourne Research Collaboration grant, and University of British Columbia’s Centre for Hip Health and Mobility via the Society for Mobility and Health. One study author is president of Boston Imaging Core Lab, LLC, and is a consultant to Merck Serono, Sanofi-Aventis, Genzyme and TissueGene. No other authors declared conflicts of interest.
People who have had a knee reconstruction following trauma may be susceptible to osteoarthritis sooner than currently thought, according to new MRI findings at 1 year after anterior cruciate ligament reconstruction.
Almost a third of people studied had some evidence of early osteoarthritis (OA) at that early time point, challenging “existing dogma that degenerative joint disease does not become apparent for years post-ACLR,” reported Dr. Kay Crossley of the University of Queensland in Brisbane, Australia (Arthritis Rheumatol. 2015 Feb. 18 [doi:10.1002/art.39005]).
However, as they did not have access to preoperative images, they could not rule out that some OA features may have been preexisting and not related to knee trauma, they said.
“This is a sample that was taken after the injury and after the reconstruction, so they truly don’t know that what they’re finding is as a result of even the injury, surgery, or the meniscal damage or meniscal resection they had done at the time,” Dr. David J. Hunter, a leading OA expert from Sydney (Australia) University, said when asked to comment on the study’s findings.
“It may well be that these were people that had some underlying structural damage,” he added.
The researchers noted that radiographic knee OA was thought to be as high as 50%-90% a decade after anterior cruciate ligament reconstruction (ACLR). The issue is particularly important because ACL injuries typically occur in younger adults who are then prone to developing knee OA before they reach 40 years, they said.
“Early detection of knee OA after ACLR may permit early intervention such as load management, which is likely to be more effective prior to the development of advanced disease,” they wrote.
Their study included 111 patients aged 18-50 years who had undergone single-bundle hamstring-tendon autograft ACLR 1 year earlier.
MRI scans of their knees were compared with 20 uninjured asymptomatic matched controls. The researchers used the MRI Osteoarthritis Knee Score (MOAKS) to score specific OA features because the more recent Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) had not been published at the time of their study.
Results showed that 34 (31%) patients had MRI-defined knee OA following an ACLR a year earlier.
MRI-OA features were most frequently found in the patellofemoral compartment, particularly the medial femoral trochlea, a potentially underrecognized site of knee pathology following reconstruction, the researchers said.
Pathology in the patellofemoral joint included not only “early” features of OA, such as bone marrow lesions and partial-thickness cartilage loss, but also frank osteophytes on MRI, they noted.
None of the uninjured control knees had MRI-defined patellofemoral or tibiofemoral OA.
The authors acknowledged that a lack of access to preoperative knee images limited the conclusions they could reach in their study, but they noted that MRI-OA features were rarely seen in the small sample of uninjured matched control knees.
“Combined with the observation that six times as many reconstructed knees had radiographic osteophytes than uninjured contralateral knees, these findings suggest that knee trauma and/or reconstruction was strongly implicated in the development of OA features,” they wrote.
Another limitation that the authors acknowledged was that the MRI definition of OA was relatively new and was likely to be refined as the understanding of OA pathology evolved.
Dr. Hunter, who was the lead investigator involved in developing the MOAKS, agreed that the definition needed more validity and testing.
“This is the third study that uses that definition, and I do think that long-term clinical implications of what MRI definition means is unknown,” he said. “The challenge that we have is that we do kick up a lot of abnormalities, and we don’t truly know what the long-term clinical implications of those abnormalities are at this point.”
“There are a lot of problems with the way this study has been done, but I do think it is really helpful that it highlights how important injury is with regards to predisposing to early OA.”
“It’s something that a lot of people don’t really highlight or pay attention to,” he said.
The study was partly funded by the Queensland Orthopaedic Physiotherapy Network, a University of Melbourne Research Collaboration grant, and University of British Columbia’s Centre for Hip Health and Mobility via the Society for Mobility and Health. One study author is president of Boston Imaging Core Lab, LLC, and is a consultant to Merck Serono, Sanofi-Aventis, Genzyme and TissueGene. No other authors declared conflicts of interest.
People who have had a knee reconstruction following trauma may be susceptible to osteoarthritis sooner than currently thought, according to new MRI findings at 1 year after anterior cruciate ligament reconstruction.
Almost a third of people studied had some evidence of early osteoarthritis (OA) at that early time point, challenging “existing dogma that degenerative joint disease does not become apparent for years post-ACLR,” reported Dr. Kay Crossley of the University of Queensland in Brisbane, Australia (Arthritis Rheumatol. 2015 Feb. 18 [doi:10.1002/art.39005]).
However, as they did not have access to preoperative images, they could not rule out that some OA features may have been preexisting and not related to knee trauma, they said.
“This is a sample that was taken after the injury and after the reconstruction, so they truly don’t know that what they’re finding is as a result of even the injury, surgery, or the meniscal damage or meniscal resection they had done at the time,” Dr. David J. Hunter, a leading OA expert from Sydney (Australia) University, said when asked to comment on the study’s findings.
“It may well be that these were people that had some underlying structural damage,” he added.
The researchers noted that radiographic knee OA was thought to be as high as 50%-90% a decade after anterior cruciate ligament reconstruction (ACLR). The issue is particularly important because ACL injuries typically occur in younger adults who are then prone to developing knee OA before they reach 40 years, they said.
“Early detection of knee OA after ACLR may permit early intervention such as load management, which is likely to be more effective prior to the development of advanced disease,” they wrote.
Their study included 111 patients aged 18-50 years who had undergone single-bundle hamstring-tendon autograft ACLR 1 year earlier.
MRI scans of their knees were compared with 20 uninjured asymptomatic matched controls. The researchers used the MRI Osteoarthritis Knee Score (MOAKS) to score specific OA features because the more recent Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) had not been published at the time of their study.
Results showed that 34 (31%) patients had MRI-defined knee OA following an ACLR a year earlier.
MRI-OA features were most frequently found in the patellofemoral compartment, particularly the medial femoral trochlea, a potentially underrecognized site of knee pathology following reconstruction, the researchers said.
Pathology in the patellofemoral joint included not only “early” features of OA, such as bone marrow lesions and partial-thickness cartilage loss, but also frank osteophytes on MRI, they noted.
None of the uninjured control knees had MRI-defined patellofemoral or tibiofemoral OA.
The authors acknowledged that a lack of access to preoperative knee images limited the conclusions they could reach in their study, but they noted that MRI-OA features were rarely seen in the small sample of uninjured matched control knees.
“Combined with the observation that six times as many reconstructed knees had radiographic osteophytes than uninjured contralateral knees, these findings suggest that knee trauma and/or reconstruction was strongly implicated in the development of OA features,” they wrote.
Another limitation that the authors acknowledged was that the MRI definition of OA was relatively new and was likely to be refined as the understanding of OA pathology evolved.
Dr. Hunter, who was the lead investigator involved in developing the MOAKS, agreed that the definition needed more validity and testing.
“This is the third study that uses that definition, and I do think that long-term clinical implications of what MRI definition means is unknown,” he said. “The challenge that we have is that we do kick up a lot of abnormalities, and we don’t truly know what the long-term clinical implications of those abnormalities are at this point.”
“There are a lot of problems with the way this study has been done, but I do think it is really helpful that it highlights how important injury is with regards to predisposing to early OA.”
“It’s something that a lot of people don’t really highlight or pay attention to,” he said.
The study was partly funded by the Queensland Orthopaedic Physiotherapy Network, a University of Melbourne Research Collaboration grant, and University of British Columbia’s Centre for Hip Health and Mobility via the Society for Mobility and Health. One study author is president of Boston Imaging Core Lab, LLC, and is a consultant to Merck Serono, Sanofi-Aventis, Genzyme and TissueGene. No other authors declared conflicts of interest.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: People who have undergone anterior cruciate ligament reconstruction following trauma may be susceptible to early OA sooner than previously thought, but the study authors did not have access to baseline images to rule out existing pathology.
Major finding: A third of the 111 patients studied had evidence of MRI-defined OA a year after their surgery.
Data source: MRI study of 111 patients who had undergone ACL surgery matched with 20 uninjured asymptomatic controls.
Disclosures: The study was partly funded by the Queensland Orthopaedic Physiotherapy Network, a University of Melbourne Research Collaboration grant, and University of British Columbia’s Centre for Hip Health and Mobility via the Society for Mobility and Health. One study author is president of Boston Imaging Core Lab, LLC, and is a consultant to Merck Serono, Sanofi-Aventis, Genzyme and TissueGene. No other authors declared conflicts of interest.
Lung cancer screening criteria may need changes
Fewer patients diagnosed with lung cancer are meeting the U.S. Preventive Services Task Force criteria for screening with low-dose computed tomography (LDCT).
Screening criteria may need to be changed, since fewer American adults now have a smoking history of 30-pack years and have quit within the last 15 years, according to Dr. Ping Yang of the division of epidemiology at the Mayo Clinic, Rochester, Minn., and her colleagues.
A retrospective analysis of patients with pathologically confirmed lung cancer in Olmsted County, Minn., between 1984 and 2011 found that in 1984-1990, 57% of patients with diagnosed lung cancer met USPSTF screening guidelines. By 2005-2011, the figure had dropped significantly to 43%.
The proportion of women who would have been eligible under the criteria decreased from 52% to 37% in the same time period; the proportion of men had dropped from 60% to 50%, they found.
“More sensitive screening criteria may need to be identified while balancing the potential harm from computed tomography,” Dr. Yang and her colleagues wrote (JAMA 2015 Feb. 24;313:853-5).
Lung cancer incidence trends in this study were comparable with Surveillance, Epidemiology and End Results data, but may not be generalizable to the U.S. population, they added.The study was funded by the National Institutes of Health and the Mayo Clinic Foundation. The authors reported no relevant conflicts of interest.
Fewer patients diagnosed with lung cancer are meeting the U.S. Preventive Services Task Force criteria for screening with low-dose computed tomography (LDCT).
Screening criteria may need to be changed, since fewer American adults now have a smoking history of 30-pack years and have quit within the last 15 years, according to Dr. Ping Yang of the division of epidemiology at the Mayo Clinic, Rochester, Minn., and her colleagues.
A retrospective analysis of patients with pathologically confirmed lung cancer in Olmsted County, Minn., between 1984 and 2011 found that in 1984-1990, 57% of patients with diagnosed lung cancer met USPSTF screening guidelines. By 2005-2011, the figure had dropped significantly to 43%.
The proportion of women who would have been eligible under the criteria decreased from 52% to 37% in the same time period; the proportion of men had dropped from 60% to 50%, they found.
“More sensitive screening criteria may need to be identified while balancing the potential harm from computed tomography,” Dr. Yang and her colleagues wrote (JAMA 2015 Feb. 24;313:853-5).
Lung cancer incidence trends in this study were comparable with Surveillance, Epidemiology and End Results data, but may not be generalizable to the U.S. population, they added.The study was funded by the National Institutes of Health and the Mayo Clinic Foundation. The authors reported no relevant conflicts of interest.
Fewer patients diagnosed with lung cancer are meeting the U.S. Preventive Services Task Force criteria for screening with low-dose computed tomography (LDCT).
Screening criteria may need to be changed, since fewer American adults now have a smoking history of 30-pack years and have quit within the last 15 years, according to Dr. Ping Yang of the division of epidemiology at the Mayo Clinic, Rochester, Minn., and her colleagues.
A retrospective analysis of patients with pathologically confirmed lung cancer in Olmsted County, Minn., between 1984 and 2011 found that in 1984-1990, 57% of patients with diagnosed lung cancer met USPSTF screening guidelines. By 2005-2011, the figure had dropped significantly to 43%.
The proportion of women who would have been eligible under the criteria decreased from 52% to 37% in the same time period; the proportion of men had dropped from 60% to 50%, they found.
“More sensitive screening criteria may need to be identified while balancing the potential harm from computed tomography,” Dr. Yang and her colleagues wrote (JAMA 2015 Feb. 24;313:853-5).
Lung cancer incidence trends in this study were comparable with Surveillance, Epidemiology and End Results data, but may not be generalizable to the U.S. population, they added.The study was funded by the National Institutes of Health and the Mayo Clinic Foundation. The authors reported no relevant conflicts of interest.
FROM JAMA
Key clinical point: Changes in smoking habits may call for a revision of USPSTF lung cancer screening criteria.
Main finding: Between 2005 and 2011 only 37% of females and 50% of males diagnosed with lung cancer would have met the criteria for screening with LDCT.
Source: Retrospective analysis of 1,351 patients with lung cancer in Olmsted County, Minn., between 1984 and 2011.
Disclosures: The study was funded by NIH and the Mayo Clinic Foundation. The authors reported no relevant conflicts of interest.