User login
Psoriasiform lesions linked to anti-TNF treatment
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
VIENNA – Patients treated with an anti–tumor necrosis factor drug had a 5% annual rate of developing one or more psoriasiform skin lesions in a review of more than 400 patients who received these drugs to treat inflammatory bowel disease at a single center in Rome.
The cohort review confirmed prior reports that smoking is a risk factor for the appearance of psoriasislike skin lesions on patients being treated with an anti–tumor necrosis factor (TNF) drug, such as infliximab (Remicade) or adalimumab (Humira). The Rome experience also showed that in 28 of the 42 patients who developed a psoriasiform lesion, the eruption responded to topical treatment without need to stop or change the anti-TNF regimen. Ten of the 42 patients ultimately had to stop their anti-TNF regimen, Dr. Daniela Pugliese said at the United European Gastroenterology Global Congress.
“There have been several case reports of this, but this is the largest cohort review yet reported by one center,” said Dr. Pugliese, a gastroenterologist in the inflammatory bowel disease (IBD) unit of Complesso Integrato Columbus, Catholic University in Rome.
The review included 402 patients treated with an anti-TNF drug at the unit during 2008-2013, with a median follow-up of 17 months. During follow-up, 42 patients developed a psoriasiform lesion with a biopsy-proven diagnosis, a rate of 5 cases/100 person-years on anti-TNF treatment. The IBD patients averaged 40 years old, and 60% had Crohn’s disease and 40% had ulcerative colitis. About 60% received infliximab treatment, and 40% adalimumab. Most lesions appeared in predilection sites, as well as on palmoplantar surfaces or on the scalp; nearly half the patients had lesions in two or more locations.
A multivariate regression analysis that assessed several demographic and clinical features of all 402 patients identified two parameters that significantly linked with lesion development. Smoking linked with a greater than twofold increased risk for having a psoriasiform lesion (78 of the patients, 19%, smoked), and concurrent treatment with a thiopurine such as azathioprine, linked with a 67% reduced rate of lesion development (85 patients, 21%, were on concurrent thiopurine treatment). All IBD patients seen at the Rome unit who smoked were counseled regarding smoking cessation, Dr. Pugliese said in an interview.
Among the patients who did not respond to topical treatment, four received some benefit from starting treatment with ustekinumab (Stelara), which especially benefited patients who were otherwise difficult to treat, Dr. Pugliese said. Other patients benefited from starting treatment with cyclosporine, methotrexate, or a transient treatment with an oral steroid. Two patients who developed lesions on infliximab switched to adalimumab, and two other patients who had lesions on adalimumab switched to infliximab.
Dr. Pugliese and her associates did not have a good explanation of why patients on anti-TNF drugs develop these lesions, which Dr. Pugliese called “paradoxical.” One possible etiology is that inhibition of TNF-alpha results in uncontrolled production of interferon-alpha by plasmacytoid dendritic cells and this then triggers the psoriasiform eruptions.
A key element in managing these lesions may be early detection and topical treatment while they remain small, commented Dr. C. Janneke van der Woude, head of the IBD unit at Erasmus University Medical Center in Rotterdam, the Netherlands. “Every time we see an IBD patient who is on an anti-TNF drug, we ask whether they have had any itching, allergic reaction, arthritis, eye problem, or headache,” to facilitate early detection of an adverse effect from treatment, she said in an interview.
Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
On Twitter@mitchelzoler
AT UEG WEEK VIENNA 2014
Key clinical point: Inflammatory bowel disease patients on anti–tumor necrosis factor treatment often develop psoriasiform skin lesions.
Major finding: Patients receiving an anti-TNF drug developed psoriasiform lesions at an annual rate of 5%.
Data source: Retrospective review of 402 patients with inflammatory bowel disease treated with an anti-TNF drug at one center in Rome.
Disclosures: Dr. Pugliese had no disclosures. Dr. van der Woude said that she has been an adviser to Dr Falk, AbbVie, Janssen, Johnson & Johnson, and Cosmo.
Tocilizumab and tofacitinib increase lipids in RA patients
Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.
No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.
The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.
The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).
Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.
“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”
The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.
The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.
The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.
Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.
No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.
The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.
The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).
Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.
“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”
The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.
The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.
The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.
Rheumatoid arthritis patients treated with the biologic tocilizumab and the Janus kinase inhibitor tofacitinib had significant changes to their lipid levels in a meta-analysis of randomized, controlled trials.
No changes in lipid profiles were observed for patients taking anti–tumor necrosis factor–alpha inhibitors in the analysis of 25 randomized, controlled trials of chronic inflammatory arthritis. The study, according to lead author Alejandro Souto of the rheumatology unit at Complejo Hospitalario Universitario de Santiago (Spain) de Compostela and his colleagues, is the first study to summarize all the data about lipid changes in patients treated with biologics and tofacitinib.
The authors found that RA patients who took tocilizumab were significantly more likely to have hypercholesterolemia (>240 mg/dL), high HDL cholesterol levels (>60 mg/dL), and high LDL cholesterol levels (>130 mg/dL) at the end of the trial than did placebo patients. In RA trials, tofacitinib treatment led to significantly greater increases in levels of HDL cholesterol (13.00 mg/dL for 5 mg twice daily and 15.21 mg/dL for 10 mg twice daily) and LDL cholesterol (11.20 mg/dL for 5 mg twice daily and 15.42 mg/dL for 10 mg twice daily) than in those who took placebo, all of which were calculated with a weight mean difference (or mean percentage increase) for the continuous variable.
The exact mechanism by which the drugs affect lipid levels is unclear. “Whether the encountered changes relate to the control of inflammation or an independent mechanism of action remains to be determined,” the study authors wrote (Arthritis Rheumatol. 2014 Oct. 9 [doi:10.1002/art.38894]).
Changes in lipid levels could not be entirely explained by reduced inflammation because several drugs for RA were effective at reducing inflammation, but only tocilizumab and tofacitinib produced significant changes in lipid profiles, they noted. Results from animal models of arthritis showed decreased levels of interleukin (IL)-6 after the administration of tofacitinib, suggesting the drug may change lipid patterns by inhibiting the inflammatory cytokine.
“Interestingly, the modulation of inflammation seems to lead to lower cardiovascular events and a reduction in mortality despite increasing lipid levels,” they wrote. “It is possible that hypercholesterolemia produced by JAK [Janus kinase] inhibitors may be caused by the inhibition of IL-6 signaling.”
The long-term consequence for cardiovascular outcomes in this population should be assessed, the authors said.
The review had several limitations, which affected the generalization of their findings, the authors said. These included a lack of data on the effects of rituximab and abatacept on lipids, or in spondyloarthritis treated with biologics. It was also limited by the fact that only 25 of 307 studies contained data on lipid pattern changes and the heterogeneous way of presenting the data.
The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: The biologic tocilizumab and the JAK inhibitor increase lipid levels in RA patients.
Major finding: Tocilizumab and tofacitinib increased levels of HDL, LDL, and total cholesterol.
Data source: A systematic meta-analysis of 25 randomized, controlled trials.
Disclosures: The study was supported by an unrestricted grant from Pfizer. Two authors reported having ties to Pfizer as well as other companies that market drugs for inflammatory arthritis.
Hand exercise program worthwhile, cost effective in RA patients
A tailored hand exercise program for rheumatoid arthritis patients proved to be a cost-effective intervention for restoring and maintaining hand function in a randomized trial.
Sarah E. Lamb, D.Phil., of the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England), and her colleagues from the SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand) trial randomly assigned 490 adults with rheumatoid arthritis who reported hand pain or dysfunction to usual care or a tailored program of strengthening and stretching hand exercises at a hospital and in the home.
The exercise group’s improvement was more than double that of the usual care group. Hand function at 12 months improved by 3.6 points in the usual care group (95% confidence interval, 1.5-5.7) and 7.9 points in the exercise group (95% CI, 6.0-9.9) as measured by the Michigan Hand Outcomes Questionnaire (Lancet 2014 Oct. 10.[doi:10.1016/S0140-6736 (14)60998-3]).
The cost of the exercise program was $250 USD per patient and cost per quality-adjusted life-year was $15,316 USD.
“A tailored hand exercise program is a worthwhile, low-cost intervention as an adjunct to a range of drug regimens,” the researchers concluded.
In an accompanying editorial, Christina H. Opava, Ph.D., of the Karolinska Institute in Stockholm, and Mathilda Björk, Ph.D., of Linköping University and Jönköping University, both in Sweden, wrote that successful interventions that were also cost effective were important, particularly because RA drugs are so expensive (Lancet 2014 Oct. 10 [doi:10.1016/S0140-6736(14)61285-X]).
“The use of hand exercise also has the potential to be integrated into e-health, via a web-based solution or interactive monitoring, which could further increase cost effectiveness and adherence,” they wrote.
However the positive results of the study might be jeopardized by bias introduced by selecting patients who were motivated to travel to hospital and follow a daily exercise program at home, they said.
Before the exercise program was implemented into clinical practice, it was also important to train therapists to ensure appropriate delivery of the intervention. This was especially important as the program included the use of extensive behavioral change support techniques that are not yet self-evident parts of physical therapy and occupational therapy practice, Dr. Opava and Dr. Björk said.
The trial was funded by the U.K. National Institute for Health Research Health Technology Assessment program. None of the study or editorial authors had anything to disclose.
A tailored hand exercise program for rheumatoid arthritis patients proved to be a cost-effective intervention for restoring and maintaining hand function in a randomized trial.
Sarah E. Lamb, D.Phil., of the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England), and her colleagues from the SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand) trial randomly assigned 490 adults with rheumatoid arthritis who reported hand pain or dysfunction to usual care or a tailored program of strengthening and stretching hand exercises at a hospital and in the home.
The exercise group’s improvement was more than double that of the usual care group. Hand function at 12 months improved by 3.6 points in the usual care group (95% confidence interval, 1.5-5.7) and 7.9 points in the exercise group (95% CI, 6.0-9.9) as measured by the Michigan Hand Outcomes Questionnaire (Lancet 2014 Oct. 10.[doi:10.1016/S0140-6736 (14)60998-3]).
The cost of the exercise program was $250 USD per patient and cost per quality-adjusted life-year was $15,316 USD.
“A tailored hand exercise program is a worthwhile, low-cost intervention as an adjunct to a range of drug regimens,” the researchers concluded.
In an accompanying editorial, Christina H. Opava, Ph.D., of the Karolinska Institute in Stockholm, and Mathilda Björk, Ph.D., of Linköping University and Jönköping University, both in Sweden, wrote that successful interventions that were also cost effective were important, particularly because RA drugs are so expensive (Lancet 2014 Oct. 10 [doi:10.1016/S0140-6736(14)61285-X]).
“The use of hand exercise also has the potential to be integrated into e-health, via a web-based solution or interactive monitoring, which could further increase cost effectiveness and adherence,” they wrote.
However the positive results of the study might be jeopardized by bias introduced by selecting patients who were motivated to travel to hospital and follow a daily exercise program at home, they said.
Before the exercise program was implemented into clinical practice, it was also important to train therapists to ensure appropriate delivery of the intervention. This was especially important as the program included the use of extensive behavioral change support techniques that are not yet self-evident parts of physical therapy and occupational therapy practice, Dr. Opava and Dr. Björk said.
The trial was funded by the U.K. National Institute for Health Research Health Technology Assessment program. None of the study or editorial authors had anything to disclose.
A tailored hand exercise program for rheumatoid arthritis patients proved to be a cost-effective intervention for restoring and maintaining hand function in a randomized trial.
Sarah E. Lamb, D.Phil., of the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences at the University of Oxford (England), and her colleagues from the SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand) trial randomly assigned 490 adults with rheumatoid arthritis who reported hand pain or dysfunction to usual care or a tailored program of strengthening and stretching hand exercises at a hospital and in the home.
The exercise group’s improvement was more than double that of the usual care group. Hand function at 12 months improved by 3.6 points in the usual care group (95% confidence interval, 1.5-5.7) and 7.9 points in the exercise group (95% CI, 6.0-9.9) as measured by the Michigan Hand Outcomes Questionnaire (Lancet 2014 Oct. 10.[doi:10.1016/S0140-6736 (14)60998-3]).
The cost of the exercise program was $250 USD per patient and cost per quality-adjusted life-year was $15,316 USD.
“A tailored hand exercise program is a worthwhile, low-cost intervention as an adjunct to a range of drug regimens,” the researchers concluded.
In an accompanying editorial, Christina H. Opava, Ph.D., of the Karolinska Institute in Stockholm, and Mathilda Björk, Ph.D., of Linköping University and Jönköping University, both in Sweden, wrote that successful interventions that were also cost effective were important, particularly because RA drugs are so expensive (Lancet 2014 Oct. 10 [doi:10.1016/S0140-6736(14)61285-X]).
“The use of hand exercise also has the potential to be integrated into e-health, via a web-based solution or interactive monitoring, which could further increase cost effectiveness and adherence,” they wrote.
However the positive results of the study might be jeopardized by bias introduced by selecting patients who were motivated to travel to hospital and follow a daily exercise program at home, they said.
Before the exercise program was implemented into clinical practice, it was also important to train therapists to ensure appropriate delivery of the intervention. This was especially important as the program included the use of extensive behavioral change support techniques that are not yet self-evident parts of physical therapy and occupational therapy practice, Dr. Opava and Dr. Björk said.
The trial was funded by the U.K. National Institute for Health Research Health Technology Assessment program. None of the study or editorial authors had anything to disclose.
FROM THE LANCET
Key clinical point: A tailored hand exercise program for RA patients is a cost-effective intervention for restoring hand function.
Major finding: Hand function at 12 months improved by 3.6 points in the usual care group (95% CI, 1.5-5.7) and 7.9 points in the exercise group (95% CI, 6.0-9.9) as measured by the Michigan Hand Outcomes Questionnaire
Data source: A multicenter, randomized trial of 490 RA patients assigned to usual care or a hand exercise program.
Disclosures: The trial was funded by the U.K. National Institute for Health Research Health Technology Assessment program. None of the authors had anything to disclose.
Biomarkers identify RA patients at risk of lung disease
An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.
Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).
They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).
The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”
Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.
“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.
Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.
The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.
*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.
An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.
Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).
They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).
The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”
Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.
“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.
Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.
The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.
*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.
An international team of researchers has identified biomarkers that may help pinpoint rheumatoid arthritis patients at risk of interstitial lung disease.
Dr. Juan Chen of the First Hospital of Xiamen (China) University and Dr. Tracy Doyle of Brigham and Women’s Hospital, Boston, classified Chinese rheumatoid arthritis (RA) patients into different clinical and radiographic stages of interstitial lung disease (ILD) – RA with no ILD, RA with mild ILD, and RA with advanced ILD (Arthritis Rheumatol. 2014 [doi:10.1002/art.38904]).
They used multiplex ELISA (enzyme-linked immunosorbent assay) to identify strong correlations between average serum levels of MMP-7 and IP10 and the grade of interstitial lung abnormalities. The average serum concentration of MMP-7 increased from 3.06 ng/mL in the RA patients with no ILD to 5.35 ng/mL in RA patients with ILD (P = .005). Levels of IP10 increased from 173.8 pg/mL in RA patients with no lung disease to 308.6 pg/mL in patients with ILD (P = .0004).
The researchers also found statistically significant elevations of both biomarkers in the patients with mild disease, “strengthening the apparent dose response relationship between these biomarkers and severity of radiographically defined interstitial lung abnormalities.”
Using a replication cohort from two academic centers in the United States, the researchers confirmed their findings by identifying statistically significant correlations between the two biomarkers and the presence of lung disease. The findings held strong even after adjustment for age, sex, smoking history, and 28-joint Disease Activity Score.
“[The results] demonstrate that elevated levels of IP10 and MMP-7 strongly correlate with the presence of RA-ILD, effectively supporting the hypothesis that RA-ILD represents a spectrum of pathology involving parenchymal lung inflammation and dysregulated tissue remodeling,” the study authors concluded.
Longitudinal studies are needed to determine the prognostic value of MMP-7 and IP10 in RA patients with clinically/radiographically established disease, “potentially enabling clinicians to distinguish those individuals most likely to develop progressive fibrosis and an IPF-like clinical course,” they added.
The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.
*Correction 10/30/2014: The article previously listed the Rheumatology Research Foundation under its old name, the American College of Rheumatology Research and Education Foundation.
FROM ARTHRITIS AND RHEUMATOLOGY
Key clinical point: The discovery of blood biomarkers may lead to early identification of lung complications in RA patients.
Major finding: MMP-7 and IP10 were elevated in the blood of patients with different stages of RA associated interstitial lung disease.
Data source: A Chinese identification cohort (n = 133) and a U.S. replication cohort (n = 86) of RA patients with or without ILD.
Disclosures: The research was supported in part by the Harvard KL2/Catalyst Medical Research Investigator Training Program as well as grants from the National Institutes of Health, Veterans Affairs Merit Review Program, and the *Rheumatology Research Foundation’s Within Our Reach program. No conflicts of interest were declared.
RA patients’ readmission rates after joint replacement are rising
Rheumatoid arthritis patients who have undergone a hip or knee replacement are more likely to be readmitted to a hospital than are patients with osteoarthritis, according to findings from a large prospective registry study.
The analysis revealed an increasing trend in the incidence of 90-day readmissions in the rheumatoid arthritis (RA) patients by year, at 5.8%, 8.9%, and 10.6% for 2009, 2010, and 2011, respectively, Dr. Jasvinder Singh of the Birmingham (Ala.) VA Medical Center and his colleagues reported (Arthritis Care Res. 2014 Oct. 9 [doi:10.1002/acr.22497]).
For osteoarthritis (OA) patients, the 90-day readmission rates were similar by year at 6.7%, 6.7%, and 6.8%, respectively. After accounting for differences, including the risk by year, the adjusted risk for 90-day readmission in RA patients was 0.89 (95% confidence interval, 0.46-1.71) in 2009, 1.34 (95% CI, 0.69-2.61) in 2010, and 1.74 (95% CI, 1.16-2.60) in 2011, compared with OA patients.
Readmission after an elective hip or knee replacement is a problem of significant public health proportions, the study authors noted. A 90-day readmission rate of 6.8% translates to more than 70,000 admissions annually in the United States, they said.
The investigators analyzed 34,311 joint replacement procedures during the 3-year period – 33,815 performed in OA patients and 496 in patients with RA.
Overall, 42 RA patients were readmitted over the 3-year period, and the two most common reasons for readmission were joint prosthesis infection (10.2%) and septicemia (10.2%). For the 2,277 OA patients who were readmitted, the most common reasons were joint prosthesis infection (5.7%) and other postoperative infections.
The finding of an increasing 90-day readmission over a 3-year period in RA patients was a particular concern. “We considered several patient, procedure, surgeon, and hospital variables as important covariates and adjusted for those that were significant (age, gender, American Society of Anesthesiologists category, and iron deficiency anemia) in our multivariable-adjusted model, indicating that the increasing readmission rate in RA patients is not explained by these variables,” they wrote.
The effects of medications and pre- and postoperative rehabilitation programs could have played a role in readmission rates in RA patients, but the authors did not have the information to analyze the impact of these factors.
No conflicts of interest were declared.
Rheumatoid arthritis patients who have undergone a hip or knee replacement are more likely to be readmitted to a hospital than are patients with osteoarthritis, according to findings from a large prospective registry study.
The analysis revealed an increasing trend in the incidence of 90-day readmissions in the rheumatoid arthritis (RA) patients by year, at 5.8%, 8.9%, and 10.6% for 2009, 2010, and 2011, respectively, Dr. Jasvinder Singh of the Birmingham (Ala.) VA Medical Center and his colleagues reported (Arthritis Care Res. 2014 Oct. 9 [doi:10.1002/acr.22497]).
For osteoarthritis (OA) patients, the 90-day readmission rates were similar by year at 6.7%, 6.7%, and 6.8%, respectively. After accounting for differences, including the risk by year, the adjusted risk for 90-day readmission in RA patients was 0.89 (95% confidence interval, 0.46-1.71) in 2009, 1.34 (95% CI, 0.69-2.61) in 2010, and 1.74 (95% CI, 1.16-2.60) in 2011, compared with OA patients.
Readmission after an elective hip or knee replacement is a problem of significant public health proportions, the study authors noted. A 90-day readmission rate of 6.8% translates to more than 70,000 admissions annually in the United States, they said.
The investigators analyzed 34,311 joint replacement procedures during the 3-year period – 33,815 performed in OA patients and 496 in patients with RA.
Overall, 42 RA patients were readmitted over the 3-year period, and the two most common reasons for readmission were joint prosthesis infection (10.2%) and septicemia (10.2%). For the 2,277 OA patients who were readmitted, the most common reasons were joint prosthesis infection (5.7%) and other postoperative infections.
The finding of an increasing 90-day readmission over a 3-year period in RA patients was a particular concern. “We considered several patient, procedure, surgeon, and hospital variables as important covariates and adjusted for those that were significant (age, gender, American Society of Anesthesiologists category, and iron deficiency anemia) in our multivariable-adjusted model, indicating that the increasing readmission rate in RA patients is not explained by these variables,” they wrote.
The effects of medications and pre- and postoperative rehabilitation programs could have played a role in readmission rates in RA patients, but the authors did not have the information to analyze the impact of these factors.
No conflicts of interest were declared.
Rheumatoid arthritis patients who have undergone a hip or knee replacement are more likely to be readmitted to a hospital than are patients with osteoarthritis, according to findings from a large prospective registry study.
The analysis revealed an increasing trend in the incidence of 90-day readmissions in the rheumatoid arthritis (RA) patients by year, at 5.8%, 8.9%, and 10.6% for 2009, 2010, and 2011, respectively, Dr. Jasvinder Singh of the Birmingham (Ala.) VA Medical Center and his colleagues reported (Arthritis Care Res. 2014 Oct. 9 [doi:10.1002/acr.22497]).
For osteoarthritis (OA) patients, the 90-day readmission rates were similar by year at 6.7%, 6.7%, and 6.8%, respectively. After accounting for differences, including the risk by year, the adjusted risk for 90-day readmission in RA patients was 0.89 (95% confidence interval, 0.46-1.71) in 2009, 1.34 (95% CI, 0.69-2.61) in 2010, and 1.74 (95% CI, 1.16-2.60) in 2011, compared with OA patients.
Readmission after an elective hip or knee replacement is a problem of significant public health proportions, the study authors noted. A 90-day readmission rate of 6.8% translates to more than 70,000 admissions annually in the United States, they said.
The investigators analyzed 34,311 joint replacement procedures during the 3-year period – 33,815 performed in OA patients and 496 in patients with RA.
Overall, 42 RA patients were readmitted over the 3-year period, and the two most common reasons for readmission were joint prosthesis infection (10.2%) and septicemia (10.2%). For the 2,277 OA patients who were readmitted, the most common reasons were joint prosthesis infection (5.7%) and other postoperative infections.
The finding of an increasing 90-day readmission over a 3-year period in RA patients was a particular concern. “We considered several patient, procedure, surgeon, and hospital variables as important covariates and adjusted for those that were significant (age, gender, American Society of Anesthesiologists category, and iron deficiency anemia) in our multivariable-adjusted model, indicating that the increasing readmission rate in RA patients is not explained by these variables,” they wrote.
The effects of medications and pre- and postoperative rehabilitation programs could have played a role in readmission rates in RA patients, but the authors did not have the information to analyze the impact of these factors.
No conflicts of interest were declared.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: The 90-day risk of readmission after hip or knee replacement surgery is higher in patients with RA, compared with patients with OA.
Major finding: Readmissions for RA patients climbed significantly each year studied, compared with OA patients.
Data source: A prospective analysis of data from a total joint replacement registry of adults with OA and RA.
Disclosures: No conflicts of interest were declared.
Nintedanib, pirfenidone approved for pulmonary fibrosis
The Food and Drug Administration on Oct. 15 approved two new oral medications for idiopathic pulmonary fibrosis, Boehringer Ingelheim’s nintedanib (Ofev) and Roche’s pirfenidone (Esbriet).
The drugs significantly slowed the decline of forced vital capacity (FVC), compared with placebo, in phase III testing. They did not significantly reduce mortality. The FDA granted both agents fast track, priority review, orphan product, and breakthrough designations. Both were also approved ahead of schedule, according to the agency. Each of the drugs should be available for patients within the next 2 weeks, according to their manufacturers.
For pirfenidone, already on the market in Europe and Canada, Roche said it plans “a comprehensive patient support program designed to help with access, financial support, and ongoing education.”
For nintedanib, Boehringer Ingelheim plans “a comprehensive patient support program that will provide a broad range of financial and nursing support services,” called “Open Doors.” In testing, the most frequent serious adverse reactions with nintedanib, versus placebo, were bronchitis (1.2% versus 0.8%) and myocardial infarction (1.5% versus 0.4%). Pneumonia (0.7% versus 0.6%), lung cancer (0.3% versus 0%), and MI (0.3% versus 0.2%) were the most common fatal adverse events.
The most common side effects of nintedanib were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure. Nintedanib is not recommended for patients who have moderate to severe liver problems or are pregnancy class D. Women of childbearing potential should use contraception for at least 3 months after stopping the drug, according to the FDA.
For pirfenidone, the most serious adverse events versus placebo were liver enzyme elevations (3.7% versus 0.8%), sensitivity to light or rash (9.0% versus 1.0%), and gastrointestinal side effects that caused 2.2 % of patients to discontinue treatment compared with 1.0% of those who received placebo.
The most common side effects of pirfenidone were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, loss of appetite, gastroesophageal reflux, sinusitis, insomnia, decreased weight, and arthralgia.
The FDA warned about use of pirfenidone in patients with severe liver problems or end-stage kidney disease, or in those who require dialysis. Patients taking pirfenidone also must monitor and guard against sun exposure.
Clinical trials of pirfenidone included 1,247 idiopathic pulmonary fibrosis patients. In one with 555 patients, 17% of pirfenidone patients had an FVC decline of at least 10% after a year, compared with 32% who received placebo, Roche said.
Trials of nintedanib included 1,231 patients. One with 513 showed a relative reduction in annual FVC decline of 52% (–115 versus –240 mL for placebo) at 1 year, Boehringer Ingelheim noted.
The Food and Drug Administration on Oct. 15 approved two new oral medications for idiopathic pulmonary fibrosis, Boehringer Ingelheim’s nintedanib (Ofev) and Roche’s pirfenidone (Esbriet).
The drugs significantly slowed the decline of forced vital capacity (FVC), compared with placebo, in phase III testing. They did not significantly reduce mortality. The FDA granted both agents fast track, priority review, orphan product, and breakthrough designations. Both were also approved ahead of schedule, according to the agency. Each of the drugs should be available for patients within the next 2 weeks, according to their manufacturers.
For pirfenidone, already on the market in Europe and Canada, Roche said it plans “a comprehensive patient support program designed to help with access, financial support, and ongoing education.”
For nintedanib, Boehringer Ingelheim plans “a comprehensive patient support program that will provide a broad range of financial and nursing support services,” called “Open Doors.” In testing, the most frequent serious adverse reactions with nintedanib, versus placebo, were bronchitis (1.2% versus 0.8%) and myocardial infarction (1.5% versus 0.4%). Pneumonia (0.7% versus 0.6%), lung cancer (0.3% versus 0%), and MI (0.3% versus 0.2%) were the most common fatal adverse events.
The most common side effects of nintedanib were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure. Nintedanib is not recommended for patients who have moderate to severe liver problems or are pregnancy class D. Women of childbearing potential should use contraception for at least 3 months after stopping the drug, according to the FDA.
For pirfenidone, the most serious adverse events versus placebo were liver enzyme elevations (3.7% versus 0.8%), sensitivity to light or rash (9.0% versus 1.0%), and gastrointestinal side effects that caused 2.2 % of patients to discontinue treatment compared with 1.0% of those who received placebo.
The most common side effects of pirfenidone were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, loss of appetite, gastroesophageal reflux, sinusitis, insomnia, decreased weight, and arthralgia.
The FDA warned about use of pirfenidone in patients with severe liver problems or end-stage kidney disease, or in those who require dialysis. Patients taking pirfenidone also must monitor and guard against sun exposure.
Clinical trials of pirfenidone included 1,247 idiopathic pulmonary fibrosis patients. In one with 555 patients, 17% of pirfenidone patients had an FVC decline of at least 10% after a year, compared with 32% who received placebo, Roche said.
Trials of nintedanib included 1,231 patients. One with 513 showed a relative reduction in annual FVC decline of 52% (–115 versus –240 mL for placebo) at 1 year, Boehringer Ingelheim noted.
The Food and Drug Administration on Oct. 15 approved two new oral medications for idiopathic pulmonary fibrosis, Boehringer Ingelheim’s nintedanib (Ofev) and Roche’s pirfenidone (Esbriet).
The drugs significantly slowed the decline of forced vital capacity (FVC), compared with placebo, in phase III testing. They did not significantly reduce mortality. The FDA granted both agents fast track, priority review, orphan product, and breakthrough designations. Both were also approved ahead of schedule, according to the agency. Each of the drugs should be available for patients within the next 2 weeks, according to their manufacturers.
For pirfenidone, already on the market in Europe and Canada, Roche said it plans “a comprehensive patient support program designed to help with access, financial support, and ongoing education.”
For nintedanib, Boehringer Ingelheim plans “a comprehensive patient support program that will provide a broad range of financial and nursing support services,” called “Open Doors.” In testing, the most frequent serious adverse reactions with nintedanib, versus placebo, were bronchitis (1.2% versus 0.8%) and myocardial infarction (1.5% versus 0.4%). Pneumonia (0.7% versus 0.6%), lung cancer (0.3% versus 0%), and MI (0.3% versus 0.2%) were the most common fatal adverse events.
The most common side effects of nintedanib were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure. Nintedanib is not recommended for patients who have moderate to severe liver problems or are pregnancy class D. Women of childbearing potential should use contraception for at least 3 months after stopping the drug, according to the FDA.
For pirfenidone, the most serious adverse events versus placebo were liver enzyme elevations (3.7% versus 0.8%), sensitivity to light or rash (9.0% versus 1.0%), and gastrointestinal side effects that caused 2.2 % of patients to discontinue treatment compared with 1.0% of those who received placebo.
The most common side effects of pirfenidone were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, loss of appetite, gastroesophageal reflux, sinusitis, insomnia, decreased weight, and arthralgia.
The FDA warned about use of pirfenidone in patients with severe liver problems or end-stage kidney disease, or in those who require dialysis. Patients taking pirfenidone also must monitor and guard against sun exposure.
Clinical trials of pirfenidone included 1,247 idiopathic pulmonary fibrosis patients. In one with 555 patients, 17% of pirfenidone patients had an FVC decline of at least 10% after a year, compared with 32% who received placebo, Roche said.
Trials of nintedanib included 1,231 patients. One with 513 showed a relative reduction in annual FVC decline of 52% (–115 versus –240 mL for placebo) at 1 year, Boehringer Ingelheim noted.
Biosimilars poised to make biologics more routine
The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.
An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.
A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)
At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.
Lower cost broadens use
With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.
“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.
“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.
Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.
Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.
Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”
While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.
“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.
Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.
“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”
Concerns about safety
But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.
“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”
“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”
The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.
Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.
While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.
“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.
“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.
“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.
Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.
On Twitter @mitchelzoler
The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.
An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.
A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)
At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.
Lower cost broadens use
With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.
“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.
“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.
Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.
Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.
Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”
While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.
“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.
Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.
“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”
Concerns about safety
But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.
“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”
“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”
The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.
Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.
While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.
“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.
“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.
“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.
Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.
On Twitter @mitchelzoler
The biosimilar age for rheumatology has arrived, and experts expect wider use of previously expensive biologic drugs as biosimilar competition drives prices down and makes biologics more affordable.
An infliximab biosimilar became the first such agent to arrive onto the European market in the second half of 2013, and by the start of 2014, it was already having an impact by, for example, dropping the cost of infliximab by a third in Norway. Norway may have received the biggest biosimilar effect so far because it runs an annual auction for the best prices on competing drugs from manufacturers and then mandates Norwegian clinicians to prescribe the lowest-price option when starting a new therapy.
A U.S. version of this scenario may soon follow. In August 2014, Celltrion and Hospira, the two companies jointly producing and marketing biosimilar forms of infliximab under the names Remsima and Inflectra (in parts of eastern Europe and elsewhere), announced they had submitted a marketing application to the Food and Drug Administration. In the announcement, Celltrion officials said they expected Food and Drug Administration approval within a year. If that were to happen, and if Celltrion mounts a successful patent challenge, the Remsima form of infliximab could become one of the first biosimilars on the U.S. market. (In July, Sandoz – a subsidiary of Novartis – announced it submitted an FDA application for Zarzio, a biosimilar version of filgrastim that until now has been only available as Neupogen, a granulocyte colony–stimulating factor. Biosimilar filgrastim seems like the only contender that could edge out Remsima as the first biosimilar on the U.S. market.)
At least two more biosimilars – a third form of infliximab, and a new form of etanercept – may come next, although rheumatologists following the field caution that additional studies are needed on top of what was reported for these two biosimilars last June at the annual European Congress of Rheumatology.
Lower cost broadens use
With one rheumatology biosimilar already on several global formularies and others nearing that status, the next challenge is convincing clinicians that cut-rate biologics are safe and effective and patients can switch from the brand-name form to a biosimilar without adverse effects. Meanwhile, payers and patients are pressing for biosimilars to cut the high cost of biologic treatment. By making biologic drugs more affordable for more patients, introduction of biosimilars will change patient care, experts said.
“A decrease in price will change how biologics are used in U.S. patients. In the United States today, about half of rheumatoid arthritis (RA) patients receive a biologic,” a rate substantially below where it should be, said Dr. Vibeke Strand, a biopharmaceutical consultant and rheumatologist at Stanford (Calif.) University. “Biosimilars will have a very big impact,” she predicted.
“Clinicians are under a lot of pressure from pharmacies, hospitals, and managed-care organization to avoid expensive medications when possible. Starting a biologic will become easier,” when prices start falling. And adherence may also improve. “Part of why patients don’t take their biologics for more than 1-2 years is they can’t afford the copay. That may change” if prices drop, Dr. Strand said in an interview.
Before biosimilars became available, “countries with low GDPs [gross domestic products] had less access to biologics and more restrictions; richer countries had better access,” noted Dr. Tore K. Kvien, a rheumatologist and professor of rheumatology at the University of Oslo.
Greater affordability and access to biologics is the sole factor driving the biosimilar movement. “Cost is the only reason why you have biosimilars,” noted Dr. Bruce N. Cronstein, a rheumatologist and professor of medicine, pathology, and pharmacology at New York University. Aside from cost, there are, by definition, no meaningful differences between a biosimilar and the reference brand-name formulation.
Biosimilars, Dr. Cronstein said, “will be cheaper, but it won’t be like the difference with generic and brand-name statins. You won’t see a 90% price drop. Maybe we’ll see a 30% or 40% price cut, which is considerable. The biologics are all very expensive drugs. But biosimilars will not lead to anything like the savings with small generic molecules.”
While Dr. Cronstein noted that there are no guarantees regarding the timing of price changes, the extent of price cuts, or how competition might affect pricing of the brand-name alternative, the experience in Norway showed a quick, one-third price cut when Remsima became an option, Dr. Kvien said in an interview. For years, Norway has negotiated 1-year contracts for setting drug costs with manufacturers. Norwegian officials invite competitors to submit bids in an annual auction. Celltrion won the auction to make Remsima the infliximab of choice in Norway during 2014 for all six European Medicines Agency (EMA)-approved infliximab indications: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease, and ulcerative colitis.
“My colleagues tell me that the one-third reduction in price [compared with Remicade's price in 2014] was larger than they expected,” Dr. Kvien said. A year of treatment for an RA patient receiving Remsima averages about 6,000 euro now, down from the roughly 9,000 euro current annual cost for Remicade.
Dr. Strand maintained that economic pressures play a role in how easily biosimilars gain regulatory approval. For example, EMA received pressure from Eastern European countries where biologics have been relatively unavailable because of their price, she said. In the United States, pressure on the FDA comes from payers and patients because biologic copays are so high. But despite pressure, Dr. Strand and others believe that EMA and the FDA have set reasonable approval standards for biosimilars that clinicians can rely on.
“I think for all intents and purposes if EMA decides something is a biosimilar then I definitely think it is,” Dr. Strand said. “There may be subtle differences, but nothing big.” In some cases reference, brand-name biologics themselves have undergone substantial changes from what they originally had been, as happened with Enbrel and Rituxan, she noted. “The FDA will not entertain even a small change in an amino acid sequence, and requires two immunogenicity studies.”
Concerns about safety
But biosimilars may be a special case, where even the regulatory stamp of approval may not fully convince some clinicians.
“There is still quite a bit of skepticism,” Dr. Strand said. “I think there will be less skepticism once more data show that biosimilars are safe. The biggest concern seems to be that if the FDA decides something is not just biosimilar but also equivalent then there might be substitutions by a pharmacist without knowledge of the health care provider. I think there is concern because people are still not sure what biosimilar means. It will take more data to convince some people.”
“I think that physicians will be convinced by the data showing these compounds act in a similar way. What physicians worry about is that while these drugs may look good in a trial there might be some subtle difference that increases drug resistance or anaphylaxis,” said Dr. Cronstein. “I think clinicians will accept biosimilars and use them, but worry that a safety signal may not be seen in clinical trials. I think the FDA is trying to figure out how to be sure that switching from one drug to another does not cause an adverse effect. That is the major potential downside people see.”
The safety of switching to a biosimilar was an important enough issue for the Norwegian government to sponsor a 2.5 million euro trial to address the question. The 500-patient study, slated to start in the fall of 2014, will randomize patients on stable Remicade treatment to either remain on Remicade or switch to Remsima. The NOR-SWITCH trial will include patients with any of the six indications for which Remsima received EMA approval.
Until trial results are available, anticipated to be in 2016, Norway does not sanction switching patients on a stable Remicade regimen to Remsima even though Remsima is the infliximab of choice for patients starting infliximab for the first time. Despite this, some Norwegian departments have already made the switch in some patients, said Dr. Kvien, who is lead investigator for NOR-SWITCH. “They say the scientific data available now are sufficient to show switching is safe, but I do not agree.” The willingness of some Norwegian clinicians to switch their patients now from infliximab to the biosimilar shows how eager they and patients in Norway are to save money with Remsima.
While biosimilars face challenges entering and gaining traction in the European and American markets, they also seem driven by an overwhelming inevitability.
“Biosimilars will absolutely be routine in 10-20 years. They will be accepted, but it will take time,” Dr. Cronstein predicted.
“Biosimilars are here, they are not going away, and as patents run out we’ll see more and more of them,” predicted Dr. Paul Emery, professor of rheumatology at Leeds (England) University, while speaking at the annual European Congress of Rheumatology last June in Paris.
“I expect biosimilars will be important. My hope is that their lower cost will improve access to these treatments and this will mean better treatment for more patients around the world,” Dr. Kvien said.
Dr. Strand has been a consultant to Hospira, Celltrion, Amgen, Pfizer, Epirus, Baxter, and Merck Serono. Dr. Kvien has been a consultant to AbbVie, Bristol-Myers Squibb, Hospira, Celltrion, Pfizer/Wyeth, Merck Serono, Merck Sharp & Dohme, Roche, UCB, Orion, and Takeda. Dr. Cronstein has been a consultant to Pfizer and Merck Serono. Dr. Emery has been a consultant to AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and Takeda.
On Twitter @mitchelzoler
Inflammatory rheumatic diseases raise venous thromboembolism risk
Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.
The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).
Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).
“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.
The authors said that they had no conflicts of interest.
Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.
The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).
Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).
“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.
The authors said that they had no conflicts of interest.
Individuals with inflammatory rheumatic diseases such as inflammatory arthritis, vasculitis, and connective tissue diseases, have a threefold increase in the risk of venous thromboembolism, compared with the general population, according to a meta-analysis.
The meta-analysis of 25 studies – 10 of which included patients with rheumatoid arthritis (RA) – found those with RA were more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched individuals who had other comorbidities such as diabetes, peripheral vascular disease/coronary artery disease, and malignancy (OR, 2.23; 95% confidence interval, 2.02-2.47). The RA patients had a cumulative venous thromboembolism (VTE) incidence of 2.18% (Arthritis Res. Ther. 2014;16:435 [doi:10.1186/s13075-014-0435-y]).
Ten studies comprising 54,697 patients with systemic lupus erythematosus showed a cumulative thrombosis incidence of 7.29% (95% CI, 5.82%-8.75%). Other diseases for which the investigators calculated cumulative incidence rates of VTE, based on four studies apiece, were Sjögren’s syndrome (2.18%; 95% CI, 0.79%-3.57%), inflammatory myositis (4.03%; 95% CI, 2.38%-5.67%), Antineutrophil cytoplasmic antibody vasculitis (7.97%; 95% CI, 5.67%-10.28%), and systemic sclerosis (3.13%; 95% CI, 1.73%-4.52%).
“We believe that the increased VTE risk is associated with the activity of the inflammatory diseases, rather than with the treatments used for controlling the disease,” wrote Dr. Jason Lee of the University of Western Ontario, London, and Dr. Janet Pope, of the division of rheumatology at St. Joseph’s Health Care, London, Ont.
The authors said that they had no conflicts of interest.
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point: There is strong evidence for an elevated baseline risk of VTE in patients with inflammatory rheumatic diseases.
Major finding: Patients with rheumatoid arthritis are more than twice as likely to develop deep vein thrombosis or a pulmonary embolism, compared with an age- and sex-matched patients.
Data source: Meta-analysis of 25 studies.
Disclosures: No conflicts of interest were declared.
‘Prehabilitation’ cut postoperative care costs for total hip and knee replacements
Physical therapy before joint replacement surgery cut the predicted use of postoperative care by 29%, saving an estimated $1,215 in health care costs per patient, according to a Medicare claims analysis.
“These data are clinically relevant and can be used in the development of cost-effective and value-based total joint replacement programs,” said Dr. Richard Snow at OhioHealth in Columbus and his associates. The study is the first to evaluate the real-world link between preoperative physical therapy and use of postoperative care, the researchers said.
Numbers of total hip and knee replacements are projected to increase by 1.7 and 6.7 times, respectively, in the United States between 2005 and 2030, Dr. Snow and his coauthors noted. And while average length of hospital stay after these surgeries has dropped by more than 50%, there has been a substantial rise in per-patient costs of skilled nursing facilities, home health agencies, and inpatient rehabilitation, they said (J. Bone Joint Surg. 2014 Oct. 1 [doi:10.2106/JBJS.M.01285]).
The researchers analyzed 4,733 hip and knee replacement cases within a 39-county cluster of Medicare referral hospitals, and looked at the association between preoperative physical therapy (or “prehabilitation”) and use of postoperative care services in the 90 days after hospital discharge. Because of the skewed distribution of payments, the investigators looked only at cases that fell below the 95th percentile (or $41,113) for cost of care, they said.
In all, 79.7% of patients who did not undergo prehabilitation used acute care services after surgery, compared with 54.2% of patients who did (P < .0001). After controlling for comorbidities and demographic variables, prehabilitation was linked to an absolute reduction of 29% from the predicted to the observed rate of post-acute care use, saving an estimated average of $1,215 per patient, they said. Reductions in use of skilled nursing facilities, home health care services, and inpatient rehabilitation were the main drivers of the cost reduction, the researchers reported.
The findings support prior work indicating that prehabilitation can improve the value of care for patients undergoing total joint replacements, said Dr. Snow and his associates. “As the volume of arthroplasties expands within the framework of increasing health care costs, providers are under mounting pressure to identify the most cost-effective method of delivering high-quality, value-based health care,” they said.
Future studies should look at optimal ways to balance preoperative and postoperative care in specific populations of patients, the investigators said.
The research was partially supported by OhioHealth Research Institute. One or more authors reported financial relationships with biomedical entities deemed to possibly influence the research.
Physical therapy before joint replacement surgery cut the predicted use of postoperative care by 29%, saving an estimated $1,215 in health care costs per patient, according to a Medicare claims analysis.
“These data are clinically relevant and can be used in the development of cost-effective and value-based total joint replacement programs,” said Dr. Richard Snow at OhioHealth in Columbus and his associates. The study is the first to evaluate the real-world link between preoperative physical therapy and use of postoperative care, the researchers said.
Numbers of total hip and knee replacements are projected to increase by 1.7 and 6.7 times, respectively, in the United States between 2005 and 2030, Dr. Snow and his coauthors noted. And while average length of hospital stay after these surgeries has dropped by more than 50%, there has been a substantial rise in per-patient costs of skilled nursing facilities, home health agencies, and inpatient rehabilitation, they said (J. Bone Joint Surg. 2014 Oct. 1 [doi:10.2106/JBJS.M.01285]).
The researchers analyzed 4,733 hip and knee replacement cases within a 39-county cluster of Medicare referral hospitals, and looked at the association between preoperative physical therapy (or “prehabilitation”) and use of postoperative care services in the 90 days after hospital discharge. Because of the skewed distribution of payments, the investigators looked only at cases that fell below the 95th percentile (or $41,113) for cost of care, they said.
In all, 79.7% of patients who did not undergo prehabilitation used acute care services after surgery, compared with 54.2% of patients who did (P < .0001). After controlling for comorbidities and demographic variables, prehabilitation was linked to an absolute reduction of 29% from the predicted to the observed rate of post-acute care use, saving an estimated average of $1,215 per patient, they said. Reductions in use of skilled nursing facilities, home health care services, and inpatient rehabilitation were the main drivers of the cost reduction, the researchers reported.
The findings support prior work indicating that prehabilitation can improve the value of care for patients undergoing total joint replacements, said Dr. Snow and his associates. “As the volume of arthroplasties expands within the framework of increasing health care costs, providers are under mounting pressure to identify the most cost-effective method of delivering high-quality, value-based health care,” they said.
Future studies should look at optimal ways to balance preoperative and postoperative care in specific populations of patients, the investigators said.
The research was partially supported by OhioHealth Research Institute. One or more authors reported financial relationships with biomedical entities deemed to possibly influence the research.
Physical therapy before joint replacement surgery cut the predicted use of postoperative care by 29%, saving an estimated $1,215 in health care costs per patient, according to a Medicare claims analysis.
“These data are clinically relevant and can be used in the development of cost-effective and value-based total joint replacement programs,” said Dr. Richard Snow at OhioHealth in Columbus and his associates. The study is the first to evaluate the real-world link between preoperative physical therapy and use of postoperative care, the researchers said.
Numbers of total hip and knee replacements are projected to increase by 1.7 and 6.7 times, respectively, in the United States between 2005 and 2030, Dr. Snow and his coauthors noted. And while average length of hospital stay after these surgeries has dropped by more than 50%, there has been a substantial rise in per-patient costs of skilled nursing facilities, home health agencies, and inpatient rehabilitation, they said (J. Bone Joint Surg. 2014 Oct. 1 [doi:10.2106/JBJS.M.01285]).
The researchers analyzed 4,733 hip and knee replacement cases within a 39-county cluster of Medicare referral hospitals, and looked at the association between preoperative physical therapy (or “prehabilitation”) and use of postoperative care services in the 90 days after hospital discharge. Because of the skewed distribution of payments, the investigators looked only at cases that fell below the 95th percentile (or $41,113) for cost of care, they said.
In all, 79.7% of patients who did not undergo prehabilitation used acute care services after surgery, compared with 54.2% of patients who did (P < .0001). After controlling for comorbidities and demographic variables, prehabilitation was linked to an absolute reduction of 29% from the predicted to the observed rate of post-acute care use, saving an estimated average of $1,215 per patient, they said. Reductions in use of skilled nursing facilities, home health care services, and inpatient rehabilitation were the main drivers of the cost reduction, the researchers reported.
The findings support prior work indicating that prehabilitation can improve the value of care for patients undergoing total joint replacements, said Dr. Snow and his associates. “As the volume of arthroplasties expands within the framework of increasing health care costs, providers are under mounting pressure to identify the most cost-effective method of delivering high-quality, value-based health care,” they said.
Future studies should look at optimal ways to balance preoperative and postoperative care in specific populations of patients, the investigators said.
The research was partially supported by OhioHealth Research Institute. One or more authors reported financial relationships with biomedical entities deemed to possibly influence the research.
FROM JOURNAL OF BONE & JOINT SURGERY
Key clinical point: Physical therapy before total knee or total hip replacement surgeries can improve the value of care.
Major finding: In all, 79.7% of patients who did not undergo presurgical physical therapy used acute care services after surgery, compared with 54.2% of patients who underwent “prehabilitation” (P < .0001).
Data source: Medicare claims analysis of 4,733 total hip or knee replacement surgeries.
Disclosures: The research was partially supported by OhioHealth Research Institute. One or more authors reported financial relationships with biomedical entities deemed to possibly influence the research.
Musculoskeletal ultrasound increased diagnostic certainty in inflammatory arthritis
Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.
Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.
When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).
The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.
Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.
Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.
“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”
On Twitter @whitneymcknight
Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.
Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.
When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).
The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.
Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.
Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.
“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”
On Twitter @whitneymcknight
Musculoskeletal ultrasound was associated with more than double gains in diagnostic certainty in a prospective cohort of consecutive patients referred for the evaluation of inflammatory arthritis.
Consistent with previous studies, “We found that musculoskeletal ultrasound greatly increased the diagnostic certainty for inflammatory arthritis in general and for RA [rheumatoid arthritis] in particular,” wrote Dr. Hamed Rezaei and coauthors at the Karolinska Institute in Stockholm.
When the investigators added musculoskeletal ultrasound (MSUS) to the assessment of 103 previously undiagnosed persons (mean age, 50 years; 74% female) who were referred to a single center for suspected inflammatory arthritis, the percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001). Diagnostic confirmation specifically for RA went from 31.1% before MSUS to 61.2% after (P < .001). The imaging results were consistent with the final diagnosis in 95% of patients (Arthritis Res. Ther. 2014;16:448 [doi:10.1186/s13075-014-0448-6]).
The initial clinical assessments included joint examination, tests for acute-phase reactants, rheumatoid factor and anticitrullinated peptide antibody, and radiographs of hands and feet when indicated. A rheumatologist determined the probable presence of inflammatory arthritis generally, and rheumatoid arthritis specifically using a 5-point scale that assessed probability of the diagnosis with 1 point for less than a 20% probability, 2 points for greater than or equal to 20% but less than a 40% probability, and so on.
Following the initial assessment, the wrist, metacarpophalangeal, proximal interphalangeal joints 2-5 in both hands, metatarsophalangeal joints 2-5 in both feet, and any symptomatic joints, were imaged. The rheumatologist was then given the images and asked to use the same scale to once again assess the diagnostic probabilities.
Although the authors of the study pointed to the strength of their probabilistic approach to determining if musculoskeletal imaging improved diagnostic certainty on a 5-point scale, they acknowledged that the treating rheumatologist who performed the initial assessment was aware of her/his own scoring before the musculoskeletal imaging was done and may have felt either motivated to improve the result, or simply operated under the assumption that more information that may lead to increase posttest probability would be available later. However, when the cases were randomly rescored by another rheumatologist, results were reported to be almost identical.
“As expected, the likelihood of having any inflammatory arthritis and especially of having RA in patients with early arthritis symptoms increased with the presence of MSUS findings,” Dr. Rezaei and his colleagues wrote. “MSUS also improved diagnostic accuracy compared to clinical assessment alone, when analyzed in a classical (deterministic) manner; as also shown previously in more than 95% of patients there was agreement between MSUS finding and final diagnosis.”
On Twitter @whitneymcknight
FROM ARTHRITIS RESEARCH & THERAPY
Key clinical point: Musculoskeletal ultrasound can increase diagnostic certainty of inflammatory arthritis.
Major finding: The percentage of patients with a confirmed diagnosis rose from 33% before MSUS to 71.8% after (P < .001).
Data source: Multiple assessments of 103 previously undiagnosed patients with a rheumatologic condition referred to a single center.
Disclosures: Dr. Rezaei reported that he has received payment from General Electric and AbbVie. Other authors named in this study reported relationships with Bristol-Myers Squibb, General Electric, Merck Sharp & Dohme, AbbVie, Pfizer, and UCB, among others.