Rheumatoid Arthritis

Olokizumab, a humanized monoclonal antibody specific for the interleukin-6 cytokine, showed promise for patients with rheumatoid arthritis who had an inadequate response to antitumor necrosis factor therapies in a 12-week, phase II trial.

Olokizumab showed comparable efficacy to tocilizumab in this patient population and at doses in line with this class of drug. Treatment-related adverse events and laboratory profiles in the trial also were consistent with the use of an IL-6 targeted therapy in patients with moderate to severe rheumatoid arthritis.

The randomized, double-blind, placebo- and active-controlled multicenter trial of 221 patients measured changes in 28-joint and C-reactive protein Disease Activity Score (DAS28-CRP) at week 12 as its primary endpoint. Secondary endpoints included the American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates at week 12. The patients were randomly assigned to one of nine treatment arms, receiving either an intravenous subcutaneous injection of the trial drug or placebo every 2 weeks or every 4 weeks in dosages of 60 mg, 120 mg, or 240 mg, or an 8 mg/kg infusion of tocilizumab (Actemra) every 4 weeks. Patients who were not randomized to tocilizumab also received a placebo infusion every 4 weeks (Ann. Rheum. Dis. 2014 March 18 [doi:10.1136/annrheumdis-2013-204760]).

First author Dr. Mark C. Genovese of Stanford (Calif.) University and his associates found that at week 12, olokizumab produced greater reductions in baseline DAS28-CRP scores than did placebo (P less than .001), regardless of the dose tested. ACR20 and ACR50 responses were numerically higher in the test group than in placebo, but the trial was not powered to detect between-group differences in ACR endpoints. The investigators recorded ACR20 responses in 32.5%-60.7% of olokizumab-treated patients and in 17.1%-29.9% of placebo-treated patients. ACR50 responses occurred in 11.5%-33.2% of patients who received olokizumab, compared with 1.3%-4.9% of placebo patients. Few patients in any treatment arm were ACR70 responders.

Regardless of dose, olokizumab demonstrated comparable efficacy to tocilizumab across multiple endpoints. Most adverse events, such as upper respiratory infection or gastrointestinal disorders, were mild to moderate, and did not vary significantly between the two drug treatment groups.

Funding for the study was provided by UCB Pharma. Dr. Genovese disclosed he receives funding from UCB beyond the scope of this study. The other researchers involved in this study disclosed an extensive list of industry relationships.

wmcknight@frontlinemedcom.com

Olokizumab, a humanized monoclonal antibody specific for the interleukin-6 cytokine, showed promise for patients with rheumatoid arthritis who had an inadequate response to antitumor necrosis factor therapies in a 12-week, phase II trial.

Olokizumab showed comparable efficacy to tocilizumab in this patient population and at doses in line with this class of drug. Treatment-related adverse events and laboratory profiles in the trial also were consistent with the use of an IL-6 targeted therapy in patients with moderate to severe rheumatoid arthritis.

The randomized, double-blind, placebo- and active-controlled multicenter trial of 221 patients measured changes in 28-joint and C-reactive protein Disease Activity Score (DAS28-CRP) at week 12 as its primary endpoint. Secondary endpoints included the American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates at week 12. The patients were randomly assigned to one of nine treatment arms, receiving either an intravenous subcutaneous injection of the trial drug or placebo every 2 weeks or every 4 weeks in dosages of 60 mg, 120 mg, or 240 mg, or an 8 mg/kg infusion of tocilizumab (Actemra) every 4 weeks. Patients who were not randomized to tocilizumab also received a placebo infusion every 4 weeks (Ann. Rheum. Dis. 2014 March 18 [doi:10.1136/annrheumdis-2013-204760]).

First author Dr. Mark C. Genovese of Stanford (Calif.) University and his associates found that at week 12, olokizumab produced greater reductions in baseline DAS28-CRP scores than did placebo (P less than .001), regardless of the dose tested. ACR20 and ACR50 responses were numerically higher in the test group than in placebo, but the trial was not powered to detect between-group differences in ACR endpoints. The investigators recorded ACR20 responses in 32.5%-60.7% of olokizumab-treated patients and in 17.1%-29.9% of placebo-treated patients. ACR50 responses occurred in 11.5%-33.2% of patients who received olokizumab, compared with 1.3%-4.9% of placebo patients. Few patients in any treatment arm were ACR70 responders.

Regardless of dose, olokizumab demonstrated comparable efficacy to tocilizumab across multiple endpoints. Most adverse events, such as upper respiratory infection or gastrointestinal disorders, were mild to moderate, and did not vary significantly between the two drug treatment groups.

Funding for the study was provided by UCB Pharma. Dr. Genovese disclosed he receives funding from UCB beyond the scope of this study. The other researchers involved in this study disclosed an extensive list of industry relationships.

wmcknight@frontlinemedcom.com

Olokizumab, a humanized monoclonal antibody specific for the interleukin-6 cytokine, showed promise for patients with rheumatoid arthritis who had an inadequate response to antitumor necrosis factor therapies in a 12-week, phase II trial.

Olokizumab showed comparable efficacy to tocilizumab in this patient population and at doses in line with this class of drug. Treatment-related adverse events and laboratory profiles in the trial also were consistent with the use of an IL-6 targeted therapy in patients with moderate to severe rheumatoid arthritis.

The randomized, double-blind, placebo- and active-controlled multicenter trial of 221 patients measured changes in 28-joint and C-reactive protein Disease Activity Score (DAS28-CRP) at week 12 as its primary endpoint. Secondary endpoints included the American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates at week 12. The patients were randomly assigned to one of nine treatment arms, receiving either an intravenous subcutaneous injection of the trial drug or placebo every 2 weeks or every 4 weeks in dosages of 60 mg, 120 mg, or 240 mg, or an 8 mg/kg infusion of tocilizumab (Actemra) every 4 weeks. Patients who were not randomized to tocilizumab also received a placebo infusion every 4 weeks (Ann. Rheum. Dis. 2014 March 18 [doi:10.1136/annrheumdis-2013-204760]).

First author Dr. Mark C. Genovese of Stanford (Calif.) University and his associates found that at week 12, olokizumab produced greater reductions in baseline DAS28-CRP scores than did placebo (P less than .001), regardless of the dose tested. ACR20 and ACR50 responses were numerically higher in the test group than in placebo, but the trial was not powered to detect between-group differences in ACR endpoints. The investigators recorded ACR20 responses in 32.5%-60.7% of olokizumab-treated patients and in 17.1%-29.9% of placebo-treated patients. ACR50 responses occurred in 11.5%-33.2% of patients who received olokizumab, compared with 1.3%-4.9% of placebo patients. Few patients in any treatment arm were ACR70 responders.

Regardless of dose, olokizumab demonstrated comparable efficacy to tocilizumab across multiple endpoints. Most adverse events, such as upper respiratory infection or gastrointestinal disorders, were mild to moderate, and did not vary significantly between the two drug treatment groups.

Funding for the study was provided by UCB Pharma. Dr. Genovese disclosed he receives funding from UCB beyond the scope of this study. The other researchers involved in this study disclosed an extensive list of industry relationships.

wmcknight@frontlinemedcom.com

Rheumatoid arthritis patients taking an anti–tumor necrosis factor agent who had a prior hospitalization because of an infection significantly reduced their risk of a subsequent infection-related hospitalization by switching to etanercept or abatacept in a retrospective study of Medicare data.

The risk of a second hospitalization declined by 20% with abatacept (Orencia) and by 17% with etanercept (Enbrel), Huifeng Yun, Ph.D., and her colleagues reported (Ann. Rheum. Dis. 2014 March 7 [doi:10.1136/annrheumdis-2013-204011]).

"These findings provide new evidence for clinical management of high-risk RA patients and suggest that drug-specific guidance may be more appropriate when making safety-based recommendations, rather than simply lumping drugs together based on" mechanism of action, wrote Dr. Yun, an epidemiologist at the University of Birmingham, Ala., and her coauthors.

For the retrospective study, investigators examined Medicare data from 2006 to 2010 on nearly 13,000 patients with rheumatoid arthritis (RA). All of them had been hospitalized for an infection that occurred while taking a tumor necrosis factor (TNF) inhibitor and then either continued on the same medication or switched to another.

Of these, most (54.0%) were on infliximab (Remicade). Other drugs were etanercept (25.1%), adalimumab (Humira, 19.8%), certolizumab pegol (Cimzia, 0.6%), and golimumab (Simponi, 0.5%). The most common infection was pneumonia or other respiratory tract infection (30%); others included urinary tract (23%), skin/soft tissue (17%), and septicemia/bacteremia (11%).

After discharge, most started the same anti-TNF drug (79%), but 2% switched to another anti-TNF biologic, 3% switched to a non–anti-TNF biologic, and 16% didn’t get any biologic over the next 18 months. Only 10% of those who initially restarted the same anti-TNF inhibitor later switched to another biologic during follow-up.

From this primary cohort, the authors had data on 10,183 patients who received any biologic during 18 months of follow-up. During that period, 2,666 subsequent hospitalized infections occurred, with crude incidence rates ranging from of 27.1 to 34.6 per 100 person-years.

When considering the different drugs taken after hospitalization, the risk of infection was significantly lower with abatacept and etanercept, compared with infliximab (hazard ratios of 0.80 and 0.83, respectively). There were no significant associations between the types of subsequent infections and any of the drugs taken after the first infection, Dr. Yun and her colleagues said.

Another analysis seemed to indicate that the risk of a subsequent infection peaked early for etanercept, infliximab, and adalimumab and dropped off after the first 3 months. In contrast, the risk curve with abatacept and rituximab stayed fairly flat throughout follow-up, they noted.

"These findings are compatible with studies suggesting an early increased risk for anti-TNF agents that declines over time," the authors wrote. "Perhaps further accentuating these differences, the substantial majority of anti-TNF users in the analysis were restarting therapy with a medication that they had been on, whereas most abatacept and rituximab users were new users."

The findings are somewhat at odds with national recommendations, Dr. Yun and her associates pointed out. The American College of Rheumatology recommends that RA patients on anti-TNF therapy switch to a non–anti-TNF biologic after a serious adverse event, including a hospitalized infection.

"Our results suggest that the ACR recommendation may be appropriate, especially if switching to abatacept, but considering the grouped safety profile of medications defined by an anti-TNF or non–anti-TNF common [mechanism of action] may not be appropriate."

The Agency for Healthcare Research and Quality funded the study. Dr. Yun did not report any financial disclosures, but several coauthors reported numerous financial relationships with a number of pharmaceutical companies marketing drugs for RA.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Rheumatoid arthritis patients taking an anti–tumor necrosis factor agent who had a prior hospitalization because of an infection significantly reduced their risk of a subsequent infection-related hospitalization by switching to etanercept or abatacept in a retrospective study of Medicare data.

The risk of a second hospitalization declined by 20% with abatacept (Orencia) and by 17% with etanercept (Enbrel), Huifeng Yun, Ph.D., and her colleagues reported (Ann. Rheum. Dis. 2014 March 7 [doi:10.1136/annrheumdis-2013-204011]).

"These findings provide new evidence for clinical management of high-risk RA patients and suggest that drug-specific guidance may be more appropriate when making safety-based recommendations, rather than simply lumping drugs together based on" mechanism of action, wrote Dr. Yun, an epidemiologist at the University of Birmingham, Ala., and her coauthors.

For the retrospective study, investigators examined Medicare data from 2006 to 2010 on nearly 13,000 patients with rheumatoid arthritis (RA). All of them had been hospitalized for an infection that occurred while taking a tumor necrosis factor (TNF) inhibitor and then either continued on the same medication or switched to another.

Of these, most (54.0%) were on infliximab (Remicade). Other drugs were etanercept (25.1%), adalimumab (Humira, 19.8%), certolizumab pegol (Cimzia, 0.6%), and golimumab (Simponi, 0.5%). The most common infection was pneumonia or other respiratory tract infection (30%); others included urinary tract (23%), skin/soft tissue (17%), and septicemia/bacteremia (11%).

After discharge, most started the same anti-TNF drug (79%), but 2% switched to another anti-TNF biologic, 3% switched to a non–anti-TNF biologic, and 16% didn’t get any biologic over the next 18 months. Only 10% of those who initially restarted the same anti-TNF inhibitor later switched to another biologic during follow-up.

From this primary cohort, the authors had data on 10,183 patients who received any biologic during 18 months of follow-up. During that period, 2,666 subsequent hospitalized infections occurred, with crude incidence rates ranging from of 27.1 to 34.6 per 100 person-years.

When considering the different drugs taken after hospitalization, the risk of infection was significantly lower with abatacept and etanercept, compared with infliximab (hazard ratios of 0.80 and 0.83, respectively). There were no significant associations between the types of subsequent infections and any of the drugs taken after the first infection, Dr. Yun and her colleagues said.

Another analysis seemed to indicate that the risk of a subsequent infection peaked early for etanercept, infliximab, and adalimumab and dropped off after the first 3 months. In contrast, the risk curve with abatacept and rituximab stayed fairly flat throughout follow-up, they noted.

"These findings are compatible with studies suggesting an early increased risk for anti-TNF agents that declines over time," the authors wrote. "Perhaps further accentuating these differences, the substantial majority of anti-TNF users in the analysis were restarting therapy with a medication that they had been on, whereas most abatacept and rituximab users were new users."

The findings are somewhat at odds with national recommendations, Dr. Yun and her associates pointed out. The American College of Rheumatology recommends that RA patients on anti-TNF therapy switch to a non–anti-TNF biologic after a serious adverse event, including a hospitalized infection.

"Our results suggest that the ACR recommendation may be appropriate, especially if switching to abatacept, but considering the grouped safety profile of medications defined by an anti-TNF or non–anti-TNF common [mechanism of action] may not be appropriate."

The Agency for Healthcare Research and Quality funded the study. Dr. Yun did not report any financial disclosures, but several coauthors reported numerous financial relationships with a number of pharmaceutical companies marketing drugs for RA.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Rheumatoid arthritis patients taking an anti–tumor necrosis factor agent who had a prior hospitalization because of an infection significantly reduced their risk of a subsequent infection-related hospitalization by switching to etanercept or abatacept in a retrospective study of Medicare data.

The risk of a second hospitalization declined by 20% with abatacept (Orencia) and by 17% with etanercept (Enbrel), Huifeng Yun, Ph.D., and her colleagues reported (Ann. Rheum. Dis. 2014 March 7 [doi:10.1136/annrheumdis-2013-204011]).

"These findings provide new evidence for clinical management of high-risk RA patients and suggest that drug-specific guidance may be more appropriate when making safety-based recommendations, rather than simply lumping drugs together based on" mechanism of action, wrote Dr. Yun, an epidemiologist at the University of Birmingham, Ala., and her coauthors.

For the retrospective study, investigators examined Medicare data from 2006 to 2010 on nearly 13,000 patients with rheumatoid arthritis (RA). All of them had been hospitalized for an infection that occurred while taking a tumor necrosis factor (TNF) inhibitor and then either continued on the same medication or switched to another.

Of these, most (54.0%) were on infliximab (Remicade). Other drugs were etanercept (25.1%), adalimumab (Humira, 19.8%), certolizumab pegol (Cimzia, 0.6%), and golimumab (Simponi, 0.5%). The most common infection was pneumonia or other respiratory tract infection (30%); others included urinary tract (23%), skin/soft tissue (17%), and septicemia/bacteremia (11%).

After discharge, most started the same anti-TNF drug (79%), but 2% switched to another anti-TNF biologic, 3% switched to a non–anti-TNF biologic, and 16% didn’t get any biologic over the next 18 months. Only 10% of those who initially restarted the same anti-TNF inhibitor later switched to another biologic during follow-up.

From this primary cohort, the authors had data on 10,183 patients who received any biologic during 18 months of follow-up. During that period, 2,666 subsequent hospitalized infections occurred, with crude incidence rates ranging from of 27.1 to 34.6 per 100 person-years.

When considering the different drugs taken after hospitalization, the risk of infection was significantly lower with abatacept and etanercept, compared with infliximab (hazard ratios of 0.80 and 0.83, respectively). There were no significant associations between the types of subsequent infections and any of the drugs taken after the first infection, Dr. Yun and her colleagues said.

Another analysis seemed to indicate that the risk of a subsequent infection peaked early for etanercept, infliximab, and adalimumab and dropped off after the first 3 months. In contrast, the risk curve with abatacept and rituximab stayed fairly flat throughout follow-up, they noted.

"These findings are compatible with studies suggesting an early increased risk for anti-TNF agents that declines over time," the authors wrote. "Perhaps further accentuating these differences, the substantial majority of anti-TNF users in the analysis were restarting therapy with a medication that they had been on, whereas most abatacept and rituximab users were new users."

The findings are somewhat at odds with national recommendations, Dr. Yun and her associates pointed out. The American College of Rheumatology recommends that RA patients on anti-TNF therapy switch to a non–anti-TNF biologic after a serious adverse event, including a hospitalized infection.

"Our results suggest that the ACR recommendation may be appropriate, especially if switching to abatacept, but considering the grouped safety profile of medications defined by an anti-TNF or non–anti-TNF common [mechanism of action] may not be appropriate."

The Agency for Healthcare Research and Quality funded the study. Dr. Yun did not report any financial disclosures, but several coauthors reported numerous financial relationships with a number of pharmaceutical companies marketing drugs for RA.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

The investigational anti-interleukin-17 monoclonal antibody ixekizumab proved efficacious and as safe as other biologic therapies in treating rheumatoid arthritis both in patients who had never received a biologic and in patients who had an inadequate response to previous treatment with a tumor necrosis factor–alpha inhibitor, in a study recently published in Arthritis & Rheumatology.

The 12-week, phase II trial, whose results were previously reported by Dr. Mark C. Genovese at the 2012 European Congress of Rheumatology, tested five different doses of ixekizumab against placebo and found that each dose produced significantly better rates of American College of Rheumatology (ACR) 20 responses after 12 weeks than did placebo.

The ACR 20 response rates were significantly different from those produced by placebo in both biologic-naive patients and those with an inadequate response to a TNF-alpha inhibitor. The ACR 20 response rates also followed a dose-response relationship in biologic-naive patients. ACR 20 responses, as well as decreases in 28-joint Disease Activity Score and C-reactive protein levels, occurred within 3 days of starting ixekizumab. No unforeseen adverse events occurred, according to first author Dr. Genovese, of the division of immunology and rheumatology at Stanford (Calif.) University, and his coinvestigators (Arthritis Rheumatol. 2014 March 12 [doi: 10.1002/art.38617]).

More recently, investigators at the 2013 ACR annual meeting presented data from an open-label extension of the trial out to 64 weeks. ACR 20 response rates were maintained or improved after patients went on a treatment hiatus during weeks 10-16 and then restarted ixekizumab at 160 mg once every 4 weeks out through 64 weeks. In the 202 biologic-naive patients who completed the extension phase, 89% of the 107 who had an ACR 20 response at 16 weeks maintained it through 64 weeks. The corresponding rate in 99 patients formerly on TNF-alpha inhibitors was 76% of 41 patients. Those who were formerly assigned to placebo treatment had responses that were similar to those observed in patients who were originally randomized to ixekizumab in the randomized trial (Arthritis Rheum. 2013;65[Suppl. S10]:S188).

Eli Lilly sponsored the trial. Dr. Genovese reported receiving research funding and consulting compensation from Eli Lilly. Another two investigators reported receiving research grants from the company. Other investigators are or were employees of Eli Lilly.

jevans@frontlinemedcom.com

The investigational anti-interleukin-17 monoclonal antibody ixekizumab proved efficacious and as safe as other biologic therapies in treating rheumatoid arthritis both in patients who had never received a biologic and in patients who had an inadequate response to previous treatment with a tumor necrosis factor–alpha inhibitor, in a study recently published in Arthritis & Rheumatology.

The 12-week, phase II trial, whose results were previously reported by Dr. Mark C. Genovese at the 2012 European Congress of Rheumatology, tested five different doses of ixekizumab against placebo and found that each dose produced significantly better rates of American College of Rheumatology (ACR) 20 responses after 12 weeks than did placebo.

The ACR 20 response rates were significantly different from those produced by placebo in both biologic-naive patients and those with an inadequate response to a TNF-alpha inhibitor. The ACR 20 response rates also followed a dose-response relationship in biologic-naive patients. ACR 20 responses, as well as decreases in 28-joint Disease Activity Score and C-reactive protein levels, occurred within 3 days of starting ixekizumab. No unforeseen adverse events occurred, according to first author Dr. Genovese, of the division of immunology and rheumatology at Stanford (Calif.) University, and his coinvestigators (Arthritis Rheumatol. 2014 March 12 [doi: 10.1002/art.38617]).

More recently, investigators at the 2013 ACR annual meeting presented data from an open-label extension of the trial out to 64 weeks. ACR 20 response rates were maintained or improved after patients went on a treatment hiatus during weeks 10-16 and then restarted ixekizumab at 160 mg once every 4 weeks out through 64 weeks. In the 202 biologic-naive patients who completed the extension phase, 89% of the 107 who had an ACR 20 response at 16 weeks maintained it through 64 weeks. The corresponding rate in 99 patients formerly on TNF-alpha inhibitors was 76% of 41 patients. Those who were formerly assigned to placebo treatment had responses that were similar to those observed in patients who were originally randomized to ixekizumab in the randomized trial (Arthritis Rheum. 2013;65[Suppl. S10]:S188).

Eli Lilly sponsored the trial. Dr. Genovese reported receiving research funding and consulting compensation from Eli Lilly. Another two investigators reported receiving research grants from the company. Other investigators are or were employees of Eli Lilly.

jevans@frontlinemedcom.com

The investigational anti-interleukin-17 monoclonal antibody ixekizumab proved efficacious and as safe as other biologic therapies in treating rheumatoid arthritis both in patients who had never received a biologic and in patients who had an inadequate response to previous treatment with a tumor necrosis factor–alpha inhibitor, in a study recently published in Arthritis & Rheumatology.

The 12-week, phase II trial, whose results were previously reported by Dr. Mark C. Genovese at the 2012 European Congress of Rheumatology, tested five different doses of ixekizumab against placebo and found that each dose produced significantly better rates of American College of Rheumatology (ACR) 20 responses after 12 weeks than did placebo.

The ACR 20 response rates were significantly different from those produced by placebo in both biologic-naive patients and those with an inadequate response to a TNF-alpha inhibitor. The ACR 20 response rates also followed a dose-response relationship in biologic-naive patients. ACR 20 responses, as well as decreases in 28-joint Disease Activity Score and C-reactive protein levels, occurred within 3 days of starting ixekizumab. No unforeseen adverse events occurred, according to first author Dr. Genovese, of the division of immunology and rheumatology at Stanford (Calif.) University, and his coinvestigators (Arthritis Rheumatol. 2014 March 12 [doi: 10.1002/art.38617]).

More recently, investigators at the 2013 ACR annual meeting presented data from an open-label extension of the trial out to 64 weeks. ACR 20 response rates were maintained or improved after patients went on a treatment hiatus during weeks 10-16 and then restarted ixekizumab at 160 mg once every 4 weeks out through 64 weeks. In the 202 biologic-naive patients who completed the extension phase, 89% of the 107 who had an ACR 20 response at 16 weeks maintained it through 64 weeks. The corresponding rate in 99 patients formerly on TNF-alpha inhibitors was 76% of 41 patients. Those who were formerly assigned to placebo treatment had responses that were similar to those observed in patients who were originally randomized to ixekizumab in the randomized trial (Arthritis Rheum. 2013;65[Suppl. S10]:S188).

Eli Lilly sponsored the trial. Dr. Genovese reported receiving research funding and consulting compensation from Eli Lilly. Another two investigators reported receiving research grants from the company. Other investigators are or were employees of Eli Lilly.

jevans@frontlinemedcom.com

WASHINGTON – Some 64% of family physicians are "uncomfortable" or "stressed" when diagnosing autoimmune disease, and almost three-quarters said they have not been given adequate training in diagnosing and treating the conditions, according to a small survey.

The survey of 130 family physicians was conducted by the American Autoimmune Related Diseases Association (AARDA) last fall. The association has queried physicians each year since the mid-1990s on a variety of issues relating to the care and treatment of patients with any one of the 100 or so diseases that fall into the autoimmune category.

Alicia Ault/Frontline Medical News

The AARDA, along with the National Coalition of Autoimmune Patient Groups, is pushing for more comprehensive autoimmune disorder centers where patients can receive focused and coordinated care from specialists who are more intimately involved with the diseases.

The autoimmune facilities would be modeled on comprehensive cancer centers.

Now, patients struggle to find specialists who can accurately diagnose and treat their conditions. "There’s no such thing as the autoimmunologist," said Stanley Finger, Ph.D., the AARDA’s vice chairman of the board, at a briefing.

Patients responding to AARDA surveys report that it takes 4-5 years to get an accurate diagnosis, and that they see an average of five physicians before they get that diagnosis. At least half of patients are labeled chronic complainers and told that their symptoms are figments of their imagination, Dr. Finger said.

But 75% say they would seek care at a specialized center if it existed.

Improving diagnosis also requires increasing physician awareness and education. In the AARDA’s most recent survey, almost 60% of family physicians said that they had only one or two lectures on autoimmune disease in medical school, said Dr. Finger, who is also president of Environmental Consulting and Investigations in Bluffton, S.C.

"It doesn’t give a lot of time for these physicians to become experts," Dr. Finger said. "Because of that, they don’t feel very good about the training they have received."

The AARDA plans to develop a syllabus for medical schools and a continuing education program to help fill physicians’ knowledge gaps.

The group also surveys about 1,000 members of the general public every 5-7 years to gauge awareness of how patients are interacting with physicians. In 1992, only 5% could name an autoimmune disease. That has increased, but only to 15%. In the first survey, 93% of the public thought AIDS was an autoimmune disease. Now, just 21% have that belief.

Borrowing another page from the cancer model, the AARDA and the coalition are seeking to establish an autoimmune disease registry that would be similar to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. The SEER program compiles data about cancer incidence, mortality, and cost. It is widely used by researchers, patients, physicians, and public health agencies.

The autoimmune registry is still a work in progress. There is a huge absence of data in the autoimmune field – for example, no one knows with certainty just how many Americans have any of the various conditions, said Aaron H. Abend, the AARDA’s informatics director.

The registry would aggregate data already being compiled by various individual autoimmune associations. But the effort is in its infancy. The groups still need to agree on governance, data protocols, and other issues, Mr. Abend said. However, the registry will use software that is the standard for registries operated by the National Institutes of Health.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Some 64% of family physicians are "uncomfortable" or "stressed" when diagnosing autoimmune disease, and almost three-quarters said they have not been given adequate training in diagnosing and treating the conditions, according to a small survey.

The survey of 130 family physicians was conducted by the American Autoimmune Related Diseases Association (AARDA) last fall. The association has queried physicians each year since the mid-1990s on a variety of issues relating to the care and treatment of patients with any one of the 100 or so diseases that fall into the autoimmune category.

Alicia Ault/Frontline Medical News

The AARDA, along with the National Coalition of Autoimmune Patient Groups, is pushing for more comprehensive autoimmune disorder centers where patients can receive focused and coordinated care from specialists who are more intimately involved with the diseases.

The autoimmune facilities would be modeled on comprehensive cancer centers.

Now, patients struggle to find specialists who can accurately diagnose and treat their conditions. "There’s no such thing as the autoimmunologist," said Stanley Finger, Ph.D., the AARDA’s vice chairman of the board, at a briefing.

Patients responding to AARDA surveys report that it takes 4-5 years to get an accurate diagnosis, and that they see an average of five physicians before they get that diagnosis. At least half of patients are labeled chronic complainers and told that their symptoms are figments of their imagination, Dr. Finger said.

But 75% say they would seek care at a specialized center if it existed.

Improving diagnosis also requires increasing physician awareness and education. In the AARDA’s most recent survey, almost 60% of family physicians said that they had only one or two lectures on autoimmune disease in medical school, said Dr. Finger, who is also president of Environmental Consulting and Investigations in Bluffton, S.C.

"It doesn’t give a lot of time for these physicians to become experts," Dr. Finger said. "Because of that, they don’t feel very good about the training they have received."

The AARDA plans to develop a syllabus for medical schools and a continuing education program to help fill physicians’ knowledge gaps.

The group also surveys about 1,000 members of the general public every 5-7 years to gauge awareness of how patients are interacting with physicians. In 1992, only 5% could name an autoimmune disease. That has increased, but only to 15%. In the first survey, 93% of the public thought AIDS was an autoimmune disease. Now, just 21% have that belief.

Borrowing another page from the cancer model, the AARDA and the coalition are seeking to establish an autoimmune disease registry that would be similar to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. The SEER program compiles data about cancer incidence, mortality, and cost. It is widely used by researchers, patients, physicians, and public health agencies.

The autoimmune registry is still a work in progress. There is a huge absence of data in the autoimmune field – for example, no one knows with certainty just how many Americans have any of the various conditions, said Aaron H. Abend, the AARDA’s informatics director.

The registry would aggregate data already being compiled by various individual autoimmune associations. But the effort is in its infancy. The groups still need to agree on governance, data protocols, and other issues, Mr. Abend said. However, the registry will use software that is the standard for registries operated by the National Institutes of Health.

aault@frontlinemedcom.com

On Twitter @aliciaault

WASHINGTON – Some 64% of family physicians are "uncomfortable" or "stressed" when diagnosing autoimmune disease, and almost three-quarters said they have not been given adequate training in diagnosing and treating the conditions, according to a small survey.

The survey of 130 family physicians was conducted by the American Autoimmune Related Diseases Association (AARDA) last fall. The association has queried physicians each year since the mid-1990s on a variety of issues relating to the care and treatment of patients with any one of the 100 or so diseases that fall into the autoimmune category.

Alicia Ault/Frontline Medical News

The AARDA, along with the National Coalition of Autoimmune Patient Groups, is pushing for more comprehensive autoimmune disorder centers where patients can receive focused and coordinated care from specialists who are more intimately involved with the diseases.

The autoimmune facilities would be modeled on comprehensive cancer centers.

Now, patients struggle to find specialists who can accurately diagnose and treat their conditions. "There’s no such thing as the autoimmunologist," said Stanley Finger, Ph.D., the AARDA’s vice chairman of the board, at a briefing.

Patients responding to AARDA surveys report that it takes 4-5 years to get an accurate diagnosis, and that they see an average of five physicians before they get that diagnosis. At least half of patients are labeled chronic complainers and told that their symptoms are figments of their imagination, Dr. Finger said.

But 75% say they would seek care at a specialized center if it existed.

Improving diagnosis also requires increasing physician awareness and education. In the AARDA’s most recent survey, almost 60% of family physicians said that they had only one or two lectures on autoimmune disease in medical school, said Dr. Finger, who is also president of Environmental Consulting and Investigations in Bluffton, S.C.

"It doesn’t give a lot of time for these physicians to become experts," Dr. Finger said. "Because of that, they don’t feel very good about the training they have received."

The AARDA plans to develop a syllabus for medical schools and a continuing education program to help fill physicians’ knowledge gaps.

The group also surveys about 1,000 members of the general public every 5-7 years to gauge awareness of how patients are interacting with physicians. In 1992, only 5% could name an autoimmune disease. That has increased, but only to 15%. In the first survey, 93% of the public thought AIDS was an autoimmune disease. Now, just 21% have that belief.

Borrowing another page from the cancer model, the AARDA and the coalition are seeking to establish an autoimmune disease registry that would be similar to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. The SEER program compiles data about cancer incidence, mortality, and cost. It is widely used by researchers, patients, physicians, and public health agencies.

The autoimmune registry is still a work in progress. There is a huge absence of data in the autoimmune field – for example, no one knows with certainty just how many Americans have any of the various conditions, said Aaron H. Abend, the AARDA’s informatics director.

The registry would aggregate data already being compiled by various individual autoimmune associations. But the effort is in its infancy. The groups still need to agree on governance, data protocols, and other issues, Mr. Abend said. However, the registry will use software that is the standard for registries operated by the National Institutes of Health.

aault@frontlinemedcom.com

On Twitter @aliciaault

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When patients on immunosuppressive therapies need surgery, the risks of disease flare and compromised postoperative recovery and rehabilitation must be weighed against the risk of increased infections and impaired wound healing.

"I’m not sure that there is necessarily a right answer, but I think most people would stop biologic [agents] beforehand," Dr. Paul Grant said at a meeting on perioperative medicine sponsored by the University of Miami.

The decision whether to suspend a disease-modifying antirheumatic drug before surgery may depend on the individual drug and on the patient, said Dr. Grant, director of perioperative and consultative medicine at the University of Michigan Health System in Ann Arbor.

For example, it appears to be safe for patients on methotrexate to continue on therapy during elective orthopedic surgery. Evidence for this comes from a randomized clinical trial in which patients with rheumatoid arthritis (RA) were assigned to either continue on methotrexate (MTX) or suspend taking it for 2 weeks before and 2 weeks after surgery. The study also contained a control of patients with RA who were not on MTX (Ann. Rheum. Dis. 2001;60:214-7).

The investigators found that there were no significant differences in early complication rates or in complications up to 1 year of follow-up between patients who suspended or remained on MTX. Patients who stayed on the drug had significantly lower rates of RA flare.

Additionally, two systematic reviews, one looking at eight studies echoes the findings of the aforementioned randomized trial, and the other looking at four studies, in which the reviewer concluded that "continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares (Clin. Exp. Rheumatol. 2009;27:856-62) (Clin. Rheumatol. 2008;27:1217-20).None of the examined papers addresses the issue of safety in connection with comorbidities, age, or high doses of methotrexate."

"The bottom line here is that methotrexate should be continued for most surgeries. I think it might be reasonable to hold it in certain situations, for example if the patient has pretty bad kidney or liver disease, or if it’s surgery to treat a major infection," Dr. Grant said.

TNF-alpha antagonists

In contrast, the data on tumor necrosis factor–alpha (TNF-alpha) antagonists are fuzzier, with limited and conflicting information on perioperative use of these agents (etanercept, infliximab, adalimumab, certolizumab, golimumab).

"The major concern with these drugs is infection," Dr. Grant said. He pointed to a meta-analysis published in JAMA in 2006, which showed that taking the drugs doubled the risk of serious infections in general. The study did not specifically look at perioperative use of TNF-alpha antagonists (JAMA 2006;295:2275-85).

A retrospective cohort studyof 127 patients with RA who were undergoing various orthopedic procedures found that there were no differences in surgical site infections but more cases of wound dehiscence in patients who continued on the drugs, compared with those who interrupted their use perioperatively (Clin. Exp. Rheumatol. 2007;25:430-6).

A second, prospective study in 31 patients with RA undergoing foot/ankle surgery found that there were no significant differences in infection or healing between patients who interrupted therapy and those who did not (Foot Ankle Clin. 2007;12:509-24).

Other studies and systematic reviews in patients with RA or Crohn’s disease generally found no significant differences in serious infection rates, but they did detect a higher incidence of skin and soft-tissue infections among patients on anti-TNF-alpha agents vs. other disease-modifying antirheumatic drugs.

The risk of infections tends to be highest at the start of therapy with a TNF-alpha antagonist and stopping therapy is more likely to result in RA flares among patients with established disease, compared with those in the early stages of RA. Therefore, TNF blocker therapy should be restarted as soon as possible after surgery to prevent flare, Dr. Grant said.

The American College of Rheumatology and British Society of Rheumatology recommend holding TNF-alpha antagonists for one dosing cycle before major surgery. For etanercept (Enbrel), that translates to a 1-week before surgery hold, for infliximab (Remicade) 6-8 weeks, and for adalimumab (Humira) 2 weeks. These agents should also be held for 10-14 days after surgery or until wound healing is satisfactory.

"It’s probably safe to continue these medications for minor surgeries," Dr. Grant said.

Other agents

The anti-CD20 agent rituximab (Rituxan) – currently used to treat RA, vasculitis, hematologic malignancies, and other conditions – has a lower risk for bacterial infections than does TNF-alpha antagonists and has been shown to be safe in patients with a history of recurrent bacterial infections.

"Hydroxychloroquine (or Plaquenil) is felt to be safe during the preoperative period. It is recommended to continue this medication without stopping," Dr. Grant said.

There is conflicting information on infection risk with the use leflunomide (Arava), but it may be wise to stop therapy 2-4 weeks before nonurgent surgery in higher-risk patients.

There is consensus that sulfasalazine (Azulfidine) and azathioprine (Imuran) can be safely continued perioperatively, he said, although some advise holding sulfasalazine on the day of surgery.

Regarding perioperative steroids, Dr. Grant recommended determining the patient’s steroid exposure over the past year.

"Stress dose steroids are not routinely needed as long as the patients continue their normal dose. That’s really the important piece: If someone’s taking prednisone every day, make sure they take at least that dose on the day of surgery," he said.

Dr. Grant reported having no financial disclosures.

Methotrexate alone appears to be just as good as when it is combined with etanercept in reducing tender and swollen joints in patients with early inflammatory arthritis who have at least one joint with clinical synovitis, according to results from a randomized, controlled trial.

However, the combination of etanercept (Enbrel) and methotrexate (MTX) gave a more rapid clinical response that was maintained, along with responses on various imaging outcomes, in the majority of patients who stopped taking etanercept if they had no tender or swollen joints for 26 weeks or if they had reached week 52 of treatment when the primary outcome of no tender or swollen joints was measured.

A previous study has shown that the combination of methotrexate and etanercept produced greater rates of remission in patients with early rheumatoid arthritis of 4 months or less duration, but the current study, conducted by Dr. Jackie L. Nam, a clinical research fellow at the University of Leeds (England) Musculoskeletal Biomedical Research Unit and her associates, is the first to test the combination in early inflammatory arthritis (Ann. Rheum. Dis. 2014 March 11 [doi:10.1136/annrheumdis-2013-204882]).

The investigators enrolled a total of 110 patients at four centers into the trial during October 2006-May 2009. They had a mean age of 48.6 years and median symptom duration of 7 months, although all had been diagnosed within 3 months of receiving treatment in the trial. None had been treated with a synthetic or biologic disease-modifying antirheumatic drug. Most of the patients were female (76%) and many tested positive for rheumatoid factor (53%), anti-citrullinated peptide antibodies (77%), and shared epitope (82%). Most (94%) also met the 2010 ACR-EULAR (American College of Rheumatology–European League Against Rheumatism) classification criteria for rheumatoid arthritis (RA), whereas 41% met the 1987 ACR RA classification criteria. At baseline, the patients had a mean C-reactive protein Disease Activity Score (DAS28-CRP) of about 4.13 and a DAS44-CRP of 2.94.

Both groups received MTX starting at 10 mg weekly, which could then be increased by 5 mg every 4 weeks up to 20 mg and then up to a final dose of 25 mg/week if the primary outcome of no swollen or tender joints had not been reached by week 12 or thereafter. After week 52, patients could take other conventional disease-modifying antirheumatic drugs if there was ongoing disease activity. NSAIDs also were permitted throughout the trial. A single intramuscular or intra-articular corticosteroid injection equivalent to 120 mg methylprednisolone was permitted on one occasion during the first 9 months of the trial and as clinically indicated afterward.

MTX plus etanercept or MTX plus placebo led to similar rates of no tender or swollen joints at 52 weeks in patients with early inflammatory arthritis diagnosed within 3 months of treatment (32.5% vs. 28.1%, respectively). But in exploratory analyses, a significantly higher proportion of patients in the combination therapy group achieved a 28-joint, DAS28-CRP of less than 2.6 at 2 weeks than did those taking MTX monotherapy (38.5% vs. 9.2%) as well as for DAS28-CRP of 3.2 or lower (55.5% vs. 22.2%).

Initially, the investigators had hypothesized that the combination therapy group would have a 60% response rate in no tender or swollen joints at 52 weeks and the MTX monotherapy group would have a 30% response rate, but they noted that "It is likely that [no tender or swollen joints] was too strict a target and that the achievement of no swollen joints alone may have been a more realistic outcome."

There were no surprises in adverse events among the two groups, with comparable numbers occurring in the patients on combination therapy and in those on monotherapy (451.6/100 patient-years vs. 417.3, respectively) and more serious adverse events occurring among patients treated with etanercept (16.4/100 patient-years vs. 3.7), although the investigators said that many were related to medical or surgical procedures that the patients underwent.

Pfizer provided the study drug and unrestricted grant funding. Seven of the 13 investigators reported potential conflicts of interest with numerous pharmaceutical companies, including Pfizer and other companies marketing treatments for inflammatory arthritis.

jevans@frontlinemedcom.com

Methotrexate alone appears to be just as good as when it is combined with etanercept in reducing tender and swollen joints in patients with early inflammatory arthritis who have at least one joint with clinical synovitis, according to results from a randomized, controlled trial.

However, the combination of etanercept (Enbrel) and methotrexate (MTX) gave a more rapid clinical response that was maintained, along with responses on various imaging outcomes, in the majority of patients who stopped taking etanercept if they had no tender or swollen joints for 26 weeks or if they had reached week 52 of treatment when the primary outcome of no tender or swollen joints was measured.

A previous study has shown that the combination of methotrexate and etanercept produced greater rates of remission in patients with early rheumatoid arthritis of 4 months or less duration, but the current study, conducted by Dr. Jackie L. Nam, a clinical research fellow at the University of Leeds (England) Musculoskeletal Biomedical Research Unit and her associates, is the first to test the combination in early inflammatory arthritis (Ann. Rheum. Dis. 2014 March 11 [doi:10.1136/annrheumdis-2013-204882]).

The investigators enrolled a total of 110 patients at four centers into the trial during October 2006-May 2009. They had a mean age of 48.6 years and median symptom duration of 7 months, although all had been diagnosed within 3 months of receiving treatment in the trial. None had been treated with a synthetic or biologic disease-modifying antirheumatic drug. Most of the patients were female (76%) and many tested positive for rheumatoid factor (53%), anti-citrullinated peptide antibodies (77%), and shared epitope (82%). Most (94%) also met the 2010 ACR-EULAR (American College of Rheumatology–European League Against Rheumatism) classification criteria for rheumatoid arthritis (RA), whereas 41% met the 1987 ACR RA classification criteria. At baseline, the patients had a mean C-reactive protein Disease Activity Score (DAS28-CRP) of about 4.13 and a DAS44-CRP of 2.94.

Both groups received MTX starting at 10 mg weekly, which could then be increased by 5 mg every 4 weeks up to 20 mg and then up to a final dose of 25 mg/week if the primary outcome of no swollen or tender joints had not been reached by week 12 or thereafter. After week 52, patients could take other conventional disease-modifying antirheumatic drugs if there was ongoing disease activity. NSAIDs also were permitted throughout the trial. A single intramuscular or intra-articular corticosteroid injection equivalent to 120 mg methylprednisolone was permitted on one occasion during the first 9 months of the trial and as clinically indicated afterward.

MTX plus etanercept or MTX plus placebo led to similar rates of no tender or swollen joints at 52 weeks in patients with early inflammatory arthritis diagnosed within 3 months of treatment (32.5% vs. 28.1%, respectively). But in exploratory analyses, a significantly higher proportion of patients in the combination therapy group achieved a 28-joint, DAS28-CRP of less than 2.6 at 2 weeks than did those taking MTX monotherapy (38.5% vs. 9.2%) as well as for DAS28-CRP of 3.2 or lower (55.5% vs. 22.2%).

Initially, the investigators had hypothesized that the combination therapy group would have a 60% response rate in no tender or swollen joints at 52 weeks and the MTX monotherapy group would have a 30% response rate, but they noted that "It is likely that [no tender or swollen joints] was too strict a target and that the achievement of no swollen joints alone may have been a more realistic outcome."

There were no surprises in adverse events among the two groups, with comparable numbers occurring in the patients on combination therapy and in those on monotherapy (451.6/100 patient-years vs. 417.3, respectively) and more serious adverse events occurring among patients treated with etanercept (16.4/100 patient-years vs. 3.7), although the investigators said that many were related to medical or surgical procedures that the patients underwent.

Pfizer provided the study drug and unrestricted grant funding. Seven of the 13 investigators reported potential conflicts of interest with numerous pharmaceutical companies, including Pfizer and other companies marketing treatments for inflammatory arthritis.

jevans@frontlinemedcom.com

Methotrexate alone appears to be just as good as when it is combined with etanercept in reducing tender and swollen joints in patients with early inflammatory arthritis who have at least one joint with clinical synovitis, according to results from a randomized, controlled trial.

However, the combination of etanercept (Enbrel) and methotrexate (MTX) gave a more rapid clinical response that was maintained, along with responses on various imaging outcomes, in the majority of patients who stopped taking etanercept if they had no tender or swollen joints for 26 weeks or if they had reached week 52 of treatment when the primary outcome of no tender or swollen joints was measured.

A previous study has shown that the combination of methotrexate and etanercept produced greater rates of remission in patients with early rheumatoid arthritis of 4 months or less duration, but the current study, conducted by Dr. Jackie L. Nam, a clinical research fellow at the University of Leeds (England) Musculoskeletal Biomedical Research Unit and her associates, is the first to test the combination in early inflammatory arthritis (Ann. Rheum. Dis. 2014 March 11 [doi:10.1136/annrheumdis-2013-204882]).

The investigators enrolled a total of 110 patients at four centers into the trial during October 2006-May 2009. They had a mean age of 48.6 years and median symptom duration of 7 months, although all had been diagnosed within 3 months of receiving treatment in the trial. None had been treated with a synthetic or biologic disease-modifying antirheumatic drug. Most of the patients were female (76%) and many tested positive for rheumatoid factor (53%), anti-citrullinated peptide antibodies (77%), and shared epitope (82%). Most (94%) also met the 2010 ACR-EULAR (American College of Rheumatology–European League Against Rheumatism) classification criteria for rheumatoid arthritis (RA), whereas 41% met the 1987 ACR RA classification criteria. At baseline, the patients had a mean C-reactive protein Disease Activity Score (DAS28-CRP) of about 4.13 and a DAS44-CRP of 2.94.

Both groups received MTX starting at 10 mg weekly, which could then be increased by 5 mg every 4 weeks up to 20 mg and then up to a final dose of 25 mg/week if the primary outcome of no swollen or tender joints had not been reached by week 12 or thereafter. After week 52, patients could take other conventional disease-modifying antirheumatic drugs if there was ongoing disease activity. NSAIDs also were permitted throughout the trial. A single intramuscular or intra-articular corticosteroid injection equivalent to 120 mg methylprednisolone was permitted on one occasion during the first 9 months of the trial and as clinically indicated afterward.

MTX plus etanercept or MTX plus placebo led to similar rates of no tender or swollen joints at 52 weeks in patients with early inflammatory arthritis diagnosed within 3 months of treatment (32.5% vs. 28.1%, respectively). But in exploratory analyses, a significantly higher proportion of patients in the combination therapy group achieved a 28-joint, DAS28-CRP of less than 2.6 at 2 weeks than did those taking MTX monotherapy (38.5% vs. 9.2%) as well as for DAS28-CRP of 3.2 or lower (55.5% vs. 22.2%).

Initially, the investigators had hypothesized that the combination therapy group would have a 60% response rate in no tender or swollen joints at 52 weeks and the MTX monotherapy group would have a 30% response rate, but they noted that "It is likely that [no tender or swollen joints] was too strict a target and that the achievement of no swollen joints alone may have been a more realistic outcome."

There were no surprises in adverse events among the two groups, with comparable numbers occurring in the patients on combination therapy and in those on monotherapy (451.6/100 patient-years vs. 417.3, respectively) and more serious adverse events occurring among patients treated with etanercept (16.4/100 patient-years vs. 3.7), although the investigators said that many were related to medical or surgical procedures that the patients underwent.

Pfizer provided the study drug and unrestricted grant funding. Seven of the 13 investigators reported potential conflicts of interest with numerous pharmaceutical companies, including Pfizer and other companies marketing treatments for inflammatory arthritis.

jevans@frontlinemedcom.com

SNOWMASS, COLO. – During a recent 15-year period in which the annual arthroplasty rate for osteoarthritis and other noninflammatory arthritides doubled, the arthroplasty rate for rheumatoid arthritis actually declined. Moreover, the mean age at the time of arthroplasty for RA rose.

"In a time frame when utilization of total knee and total hip replacement for osteoarthritis is really skyrocketing, with younger and younger patients, I think this speaks to something pretty good going on with our RA patients," Dr. Susan M. Goodman observed at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

She presented data from a soon to be published study of nearly 2.8 million arthroplasties included in 10 state databases. The arthroplasty rate for noninflammatory arthritis – the great majority of which is osteoarthritis (OA) – zoomed from 124.5/100,000 population in 1991 to 247.5/100,000 in 2005.

Meanwhile the rate of arthroplasty for RA fell slightly, albeit statistically significantly, from 4.6 to 4.5 per 100,000. The mean age at the time of arthroplasty for RA rose from 63.4 years in 1991 to 64.9 years in 2005, reported Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York.

She turned to data from other sources to address issues related to the morbidity of arthroplasty for RA.

For example, it’s well documented that rheumatoid arthritis is associated with elevated cardiovascular risk, such that the typical RA patient has a cardiovascular morbidity burden comparable to that of someone without RA who’s 5 years older. So what does this mean for the many RA patients who come into the hospital for total hip or knee replacement?

Surprisingly, nothing. That is, data from multiple sources indicate RA patients are at no greater perioperative risk of cardiovascular events than are patients with OA undergoing the same procedures.

The take-away message? "Clearly we’re doing something right in managing our patients with RA," Dr. Goodman commented.

Similarly, an analysis of 7.75 million patients in the Nationwide Inpatient Sample database found that among RA patients undergoing intermediate-risk noncardiac surgery, such as total joint arthroplasty, the perioperative cardiovascular event rate was 0.34%, significantly less than the 1.07% rate in diabetic patients undergoing intermediate-risk surgeries. Moreover, perioperative mortality was 0.30% in the RA patients, less than half the 0.65% figure in diabetics (Arthritis Rheum. 2012;64:2429-37). These findings disproved the study hypothesis, which was that the two groups would have similar cardiovascular event rates, since both diseases are – unlike osteoarthritis – systemic inflammatory conditions associated with increased cardiovascular mortality.

"I think this means that we as rheumatologists are taking better care of our patients than the endocrinologists next door whose patients have a similar atherosclerotic burden," she continued.

Dr. Goodman was a coinvestigator in a population-based study of 351,103 total knee replacements and 157,775 total hip replacements done at 400 hospitals during 2006-2010. This retrospective analysis of an administrative database included 11,755 total knee and 5,400 total hip replacements for RA.

The prevalence of a prior history of MI, peripheral vascular disease, or cerebrovascular disease was closely similar in the RA and OA patients undergoing surgery. However, the prevalence of baseline COPD was significantly greater in the RA patients, at roughly 17.5%, or an absolute 3%-4% more than in the osteoarthritis patients.

The 30-day rates of cardiac events, venous thromboembolism, and cerebrovascular events were closely similar in the RA and OA arthroplasty patients. The RA patients undergoing total hip replacement had significantly higher rates of pulmonary compromise, infections, blood product transfusions, mechanical ventilation, and length of stay than did OA patients (Clin. Exp. Rheumatol. 2013;31:889-95). The RA patients with total knee replacement differed from their OA counterparts only in terms of greater need for transfusions and lengthier hospital stays (J. Arthroplasty 2014;29:308-13).

However, an analysis of the Hospital for Special Surgery experience failed to confirm the increased complication risks found in this study of a large administrative database. This retrospective review of adverse events within 6 months of total knee replacement in 156 RA patients and 318 OA controls showed no differences between the two groups in pneumonia, other infections, or venous thromboembolism. Moreover, the reoperation rate was 2.5% in the RA patients, compared with 8.8% in the OA group.

"The advantage of a smaller study like this is you really know who has RA and you have a lot of very granular information about the drugs they’re taking. The disadvantage, of course, is that you’re really not powered to look at major adverse events. But boy, there wasn’t even a hint of an increase in the complication rate amongst these RA patients," according to Dr. Goodman.

In a study she presented at the 2013 European Congress of Rheumatology, she compared 2-year outcomes post arthroplasty in RA and OA patients in the contemporary era of high use of biologic agents and traditional DMARDs for RA. The 178 RA patients who had total knee replacement had significantly greater comorbidities preoperatively than the 5,206 OA patients. Yet by 2 years postoperatively, they had fully caught up in terms of improved Western Ontario and McMaster Osteoarthritis Index (WOMAC) function and pain scores.

Total hip replacement was a very different story. The 202 RA patients were four times more likely to have poor WOMAC functional outcome and three times more likely to have poor pain outcome scores at 2 years, compared with 5,810 OA patients. In a multivariate analysis, higher expectations for surgery, better preoperative mental health, and more advanced education were associated with better 2-year outcomes.

"I’m not sure why our hip replacement patients with RA aren’t doing as well as the knee replacement patients, but they’re clearly not," according to the rheumatologist.

She reported having no financial disclosures.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – During a recent 15-year period in which the annual arthroplasty rate for osteoarthritis and other noninflammatory arthritides doubled, the arthroplasty rate for rheumatoid arthritis actually declined. Moreover, the mean age at the time of arthroplasty for RA rose.

"In a time frame when utilization of total knee and total hip replacement for osteoarthritis is really skyrocketing, with younger and younger patients, I think this speaks to something pretty good going on with our RA patients," Dr. Susan M. Goodman observed at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

She presented data from a soon to be published study of nearly 2.8 million arthroplasties included in 10 state databases. The arthroplasty rate for noninflammatory arthritis – the great majority of which is osteoarthritis (OA) – zoomed from 124.5/100,000 population in 1991 to 247.5/100,000 in 2005.

Meanwhile the rate of arthroplasty for RA fell slightly, albeit statistically significantly, from 4.6 to 4.5 per 100,000. The mean age at the time of arthroplasty for RA rose from 63.4 years in 1991 to 64.9 years in 2005, reported Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York.

She turned to data from other sources to address issues related to the morbidity of arthroplasty for RA.

For example, it’s well documented that rheumatoid arthritis is associated with elevated cardiovascular risk, such that the typical RA patient has a cardiovascular morbidity burden comparable to that of someone without RA who’s 5 years older. So what does this mean for the many RA patients who come into the hospital for total hip or knee replacement?

Surprisingly, nothing. That is, data from multiple sources indicate RA patients are at no greater perioperative risk of cardiovascular events than are patients with OA undergoing the same procedures.

The take-away message? "Clearly we’re doing something right in managing our patients with RA," Dr. Goodman commented.

Similarly, an analysis of 7.75 million patients in the Nationwide Inpatient Sample database found that among RA patients undergoing intermediate-risk noncardiac surgery, such as total joint arthroplasty, the perioperative cardiovascular event rate was 0.34%, significantly less than the 1.07% rate in diabetic patients undergoing intermediate-risk surgeries. Moreover, perioperative mortality was 0.30% in the RA patients, less than half the 0.65% figure in diabetics (Arthritis Rheum. 2012;64:2429-37). These findings disproved the study hypothesis, which was that the two groups would have similar cardiovascular event rates, since both diseases are – unlike osteoarthritis – systemic inflammatory conditions associated with increased cardiovascular mortality.

"I think this means that we as rheumatologists are taking better care of our patients than the endocrinologists next door whose patients have a similar atherosclerotic burden," she continued.

Dr. Goodman was a coinvestigator in a population-based study of 351,103 total knee replacements and 157,775 total hip replacements done at 400 hospitals during 2006-2010. This retrospective analysis of an administrative database included 11,755 total knee and 5,400 total hip replacements for RA.

The prevalence of a prior history of MI, peripheral vascular disease, or cerebrovascular disease was closely similar in the RA and OA patients undergoing surgery. However, the prevalence of baseline COPD was significantly greater in the RA patients, at roughly 17.5%, or an absolute 3%-4% more than in the osteoarthritis patients.

The 30-day rates of cardiac events, venous thromboembolism, and cerebrovascular events were closely similar in the RA and OA arthroplasty patients. The RA patients undergoing total hip replacement had significantly higher rates of pulmonary compromise, infections, blood product transfusions, mechanical ventilation, and length of stay than did OA patients (Clin. Exp. Rheumatol. 2013;31:889-95). The RA patients with total knee replacement differed from their OA counterparts only in terms of greater need for transfusions and lengthier hospital stays (J. Arthroplasty 2014;29:308-13).

However, an analysis of the Hospital for Special Surgery experience failed to confirm the increased complication risks found in this study of a large administrative database. This retrospective review of adverse events within 6 months of total knee replacement in 156 RA patients and 318 OA controls showed no differences between the two groups in pneumonia, other infections, or venous thromboembolism. Moreover, the reoperation rate was 2.5% in the RA patients, compared with 8.8% in the OA group.

"The advantage of a smaller study like this is you really know who has RA and you have a lot of very granular information about the drugs they’re taking. The disadvantage, of course, is that you’re really not powered to look at major adverse events. But boy, there wasn’t even a hint of an increase in the complication rate amongst these RA patients," according to Dr. Goodman.

In a study she presented at the 2013 European Congress of Rheumatology, she compared 2-year outcomes post arthroplasty in RA and OA patients in the contemporary era of high use of biologic agents and traditional DMARDs for RA. The 178 RA patients who had total knee replacement had significantly greater comorbidities preoperatively than the 5,206 OA patients. Yet by 2 years postoperatively, they had fully caught up in terms of improved Western Ontario and McMaster Osteoarthritis Index (WOMAC) function and pain scores.

Total hip replacement was a very different story. The 202 RA patients were four times more likely to have poor WOMAC functional outcome and three times more likely to have poor pain outcome scores at 2 years, compared with 5,810 OA patients. In a multivariate analysis, higher expectations for surgery, better preoperative mental health, and more advanced education were associated with better 2-year outcomes.

"I’m not sure why our hip replacement patients with RA aren’t doing as well as the knee replacement patients, but they’re clearly not," according to the rheumatologist.

She reported having no financial disclosures.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – During a recent 15-year period in which the annual arthroplasty rate for osteoarthritis and other noninflammatory arthritides doubled, the arthroplasty rate for rheumatoid arthritis actually declined. Moreover, the mean age at the time of arthroplasty for RA rose.

"In a time frame when utilization of total knee and total hip replacement for osteoarthritis is really skyrocketing, with younger and younger patients, I think this speaks to something pretty good going on with our RA patients," Dr. Susan M. Goodman observed at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

She presented data from a soon to be published study of nearly 2.8 million arthroplasties included in 10 state databases. The arthroplasty rate for noninflammatory arthritis – the great majority of which is osteoarthritis (OA) – zoomed from 124.5/100,000 population in 1991 to 247.5/100,000 in 2005.

Meanwhile the rate of arthroplasty for RA fell slightly, albeit statistically significantly, from 4.6 to 4.5 per 100,000. The mean age at the time of arthroplasty for RA rose from 63.4 years in 1991 to 64.9 years in 2005, reported Dr. Goodman, a rheumatologist at the Hospital for Special Surgery in New York.

She turned to data from other sources to address issues related to the morbidity of arthroplasty for RA.

For example, it’s well documented that rheumatoid arthritis is associated with elevated cardiovascular risk, such that the typical RA patient has a cardiovascular morbidity burden comparable to that of someone without RA who’s 5 years older. So what does this mean for the many RA patients who come into the hospital for total hip or knee replacement?

Surprisingly, nothing. That is, data from multiple sources indicate RA patients are at no greater perioperative risk of cardiovascular events than are patients with OA undergoing the same procedures.

The take-away message? "Clearly we’re doing something right in managing our patients with RA," Dr. Goodman commented.

Similarly, an analysis of 7.75 million patients in the Nationwide Inpatient Sample database found that among RA patients undergoing intermediate-risk noncardiac surgery, such as total joint arthroplasty, the perioperative cardiovascular event rate was 0.34%, significantly less than the 1.07% rate in diabetic patients undergoing intermediate-risk surgeries. Moreover, perioperative mortality was 0.30% in the RA patients, less than half the 0.65% figure in diabetics (Arthritis Rheum. 2012;64:2429-37). These findings disproved the study hypothesis, which was that the two groups would have similar cardiovascular event rates, since both diseases are – unlike osteoarthritis – systemic inflammatory conditions associated with increased cardiovascular mortality.

"I think this means that we as rheumatologists are taking better care of our patients than the endocrinologists next door whose patients have a similar atherosclerotic burden," she continued.

Dr. Goodman was a coinvestigator in a population-based study of 351,103 total knee replacements and 157,775 total hip replacements done at 400 hospitals during 2006-2010. This retrospective analysis of an administrative database included 11,755 total knee and 5,400 total hip replacements for RA.

The prevalence of a prior history of MI, peripheral vascular disease, or cerebrovascular disease was closely similar in the RA and OA patients undergoing surgery. However, the prevalence of baseline COPD was significantly greater in the RA patients, at roughly 17.5%, or an absolute 3%-4% more than in the osteoarthritis patients.

The 30-day rates of cardiac events, venous thromboembolism, and cerebrovascular events were closely similar in the RA and OA arthroplasty patients. The RA patients undergoing total hip replacement had significantly higher rates of pulmonary compromise, infections, blood product transfusions, mechanical ventilation, and length of stay than did OA patients (Clin. Exp. Rheumatol. 2013;31:889-95). The RA patients with total knee replacement differed from their OA counterparts only in terms of greater need for transfusions and lengthier hospital stays (J. Arthroplasty 2014;29:308-13).

However, an analysis of the Hospital for Special Surgery experience failed to confirm the increased complication risks found in this study of a large administrative database. This retrospective review of adverse events within 6 months of total knee replacement in 156 RA patients and 318 OA controls showed no differences between the two groups in pneumonia, other infections, or venous thromboembolism. Moreover, the reoperation rate was 2.5% in the RA patients, compared with 8.8% in the OA group.

"The advantage of a smaller study like this is you really know who has RA and you have a lot of very granular information about the drugs they’re taking. The disadvantage, of course, is that you’re really not powered to look at major adverse events. But boy, there wasn’t even a hint of an increase in the complication rate amongst these RA patients," according to Dr. Goodman.

In a study she presented at the 2013 European Congress of Rheumatology, she compared 2-year outcomes post arthroplasty in RA and OA patients in the contemporary era of high use of biologic agents and traditional DMARDs for RA. The 178 RA patients who had total knee replacement had significantly greater comorbidities preoperatively than the 5,206 OA patients. Yet by 2 years postoperatively, they had fully caught up in terms of improved Western Ontario and McMaster Osteoarthritis Index (WOMAC) function and pain scores.

Total hip replacement was a very different story. The 202 RA patients were four times more likely to have poor WOMAC functional outcome and three times more likely to have poor pain outcome scores at 2 years, compared with 5,810 OA patients. In a multivariate analysis, higher expectations for surgery, better preoperative mental health, and more advanced education were associated with better 2-year outcomes.

"I’m not sure why our hip replacement patients with RA aren’t doing as well as the knee replacement patients, but they’re clearly not," according to the rheumatologist.

She reported having no financial disclosures.

bjancin@frontlinemedcom.com

Use of tumor necrosis factor–alpha inhibitors was associated with a significant reduction in the risk of coronary artery disease in patients with rheumatoid arthritis, particularly with longer term use of the drugs, in a retrospective cohort study.

The study of 2,101 patients with incident RA diagnosed during 2001-2011 showed that those treated with a tumor necrosis factor–alpha (TNF-alpha) inhibitor alone or with methotrexate had 55% lower relative risk (95% CI, 0.21-0.96) of coronary artery disease than did a reference group treated with non-methotrexate, nonbiologic, disease-modifying antirheumatic drugs (DMARDs).

Patients treated with methotrexate alone or in combination with other nonbiologic DMARDs showed a nonsignificant 46% reduction (95% CI, 0.27-1.09) in the incidence of coronary artery disease, compared with the reference group (Arthritis Care Res. 2014;66:355-63).

There were similar trends in reduction of the risk of cardiovascular disease (CVD, defined as a composite of coronary artery disease, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure), but these did not reach statistical significance. However, the authors suggested this and the methotrexate result may have been from inadequate power.

"These findings indicate that the benefits of TNF inhibitors may extend beyond their effects on joint disease and are associated with reduction in the leading comorbidity in RA, namely CVD," wrote Dr. Androniki Bili from Geisinger Medical Center, Danville, Pa., and her colleagues.

"These benefits should be considered when weighing the risks and benefits of using these costly medications in the treatment of RA," they wrote

Patients enrolled in the study had no history of CVD prior to treatment, and the model was adjusted for a range of confounders, including age, sex, race, smoking, blood pressure, diabetes, and other cardiovascular risk factors. Median follow-up was 3.4 years.

Patients taking TNF-alpha inhibitors for 16.1 months or more had a relative risk of 0.18 for coronary artery disease (95% CI, 0.06-0.50) and 0.31 for CVD (95% CI, 0.15-0.65). There was a similar but not statistically significant trend for use of methotrexate at 23.4 months.

Subgroup analysis showed that the incidence of coronary artery disease was even lower among patients without diabetes mellitus (hazard ratio, 0.39; 95% CI, 0.15-0.98) and among rheumatoid factor–positive patients (HR, 0.38; 95% CI, 0.15-0.95), compared with the reference group.

Rheumatoid arthritis is associated with increased cardiovascular morbidity, independent of traditional cardiovascular risk factors, that is thought to be partly mediated by chronic, systemic inflammation, the researchers said.

This has led to considerable interest in the potential of medication such as TNF-alpha inhibitors in reducing this risk, particularly in light of several observational studies suggesting a reduced risk of CVD among patients treated with methotrexate.

One author was coinvestigator on two AstraZeneca clinical trials in rheumatoid arthritis, but there were no other conflicts of interest declared.

Use of tumor necrosis factor–alpha inhibitors was associated with a significant reduction in the risk of coronary artery disease in patients with rheumatoid arthritis, particularly with longer term use of the drugs, in a retrospective cohort study.

The study of 2,101 patients with incident RA diagnosed during 2001-2011 showed that those treated with a tumor necrosis factor–alpha (TNF-alpha) inhibitor alone or with methotrexate had 55% lower relative risk (95% CI, 0.21-0.96) of coronary artery disease than did a reference group treated with non-methotrexate, nonbiologic, disease-modifying antirheumatic drugs (DMARDs).

Patients treated with methotrexate alone or in combination with other nonbiologic DMARDs showed a nonsignificant 46% reduction (95% CI, 0.27-1.09) in the incidence of coronary artery disease, compared with the reference group (Arthritis Care Res. 2014;66:355-63).

There were similar trends in reduction of the risk of cardiovascular disease (CVD, defined as a composite of coronary artery disease, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure), but these did not reach statistical significance. However, the authors suggested this and the methotrexate result may have been from inadequate power.

"These findings indicate that the benefits of TNF inhibitors may extend beyond their effects on joint disease and are associated with reduction in the leading comorbidity in RA, namely CVD," wrote Dr. Androniki Bili from Geisinger Medical Center, Danville, Pa., and her colleagues.

"These benefits should be considered when weighing the risks and benefits of using these costly medications in the treatment of RA," they wrote

Patients enrolled in the study had no history of CVD prior to treatment, and the model was adjusted for a range of confounders, including age, sex, race, smoking, blood pressure, diabetes, and other cardiovascular risk factors. Median follow-up was 3.4 years.

Patients taking TNF-alpha inhibitors for 16.1 months or more had a relative risk of 0.18 for coronary artery disease (95% CI, 0.06-0.50) and 0.31 for CVD (95% CI, 0.15-0.65). There was a similar but not statistically significant trend for use of methotrexate at 23.4 months.

Subgroup analysis showed that the incidence of coronary artery disease was even lower among patients without diabetes mellitus (hazard ratio, 0.39; 95% CI, 0.15-0.98) and among rheumatoid factor–positive patients (HR, 0.38; 95% CI, 0.15-0.95), compared with the reference group.

Rheumatoid arthritis is associated with increased cardiovascular morbidity, independent of traditional cardiovascular risk factors, that is thought to be partly mediated by chronic, systemic inflammation, the researchers said.

This has led to considerable interest in the potential of medication such as TNF-alpha inhibitors in reducing this risk, particularly in light of several observational studies suggesting a reduced risk of CVD among patients treated with methotrexate.

One author was coinvestigator on two AstraZeneca clinical trials in rheumatoid arthritis, but there were no other conflicts of interest declared.

Use of tumor necrosis factor–alpha inhibitors was associated with a significant reduction in the risk of coronary artery disease in patients with rheumatoid arthritis, particularly with longer term use of the drugs, in a retrospective cohort study.

The study of 2,101 patients with incident RA diagnosed during 2001-2011 showed that those treated with a tumor necrosis factor–alpha (TNF-alpha) inhibitor alone or with methotrexate had 55% lower relative risk (95% CI, 0.21-0.96) of coronary artery disease than did a reference group treated with non-methotrexate, nonbiologic, disease-modifying antirheumatic drugs (DMARDs).

Patients treated with methotrexate alone or in combination with other nonbiologic DMARDs showed a nonsignificant 46% reduction (95% CI, 0.27-1.09) in the incidence of coronary artery disease, compared with the reference group (Arthritis Care Res. 2014;66:355-63).

There were similar trends in reduction of the risk of cardiovascular disease (CVD, defined as a composite of coronary artery disease, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure), but these did not reach statistical significance. However, the authors suggested this and the methotrexate result may have been from inadequate power.

"These findings indicate that the benefits of TNF inhibitors may extend beyond their effects on joint disease and are associated with reduction in the leading comorbidity in RA, namely CVD," wrote Dr. Androniki Bili from Geisinger Medical Center, Danville, Pa., and her colleagues.

"These benefits should be considered when weighing the risks and benefits of using these costly medications in the treatment of RA," they wrote

Patients enrolled in the study had no history of CVD prior to treatment, and the model was adjusted for a range of confounders, including age, sex, race, smoking, blood pressure, diabetes, and other cardiovascular risk factors. Median follow-up was 3.4 years.

Patients taking TNF-alpha inhibitors for 16.1 months or more had a relative risk of 0.18 for coronary artery disease (95% CI, 0.06-0.50) and 0.31 for CVD (95% CI, 0.15-0.65). There was a similar but not statistically significant trend for use of methotrexate at 23.4 months.

Subgroup analysis showed that the incidence of coronary artery disease was even lower among patients without diabetes mellitus (hazard ratio, 0.39; 95% CI, 0.15-0.98) and among rheumatoid factor–positive patients (HR, 0.38; 95% CI, 0.15-0.95), compared with the reference group.

Rheumatoid arthritis is associated with increased cardiovascular morbidity, independent of traditional cardiovascular risk factors, that is thought to be partly mediated by chronic, systemic inflammation, the researchers said.

This has led to considerable interest in the potential of medication such as TNF-alpha inhibitors in reducing this risk, particularly in light of several observational studies suggesting a reduced risk of CVD among patients treated with methotrexate.

One author was coinvestigator on two AstraZeneca clinical trials in rheumatoid arthritis, but there were no other conflicts of interest declared.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.

The National Institutes of Health, 10 biopharmaceutical companies, and several nonprofit organizations have partnered to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development.

The Accelerating Medicines Partnership aims to pinpoint biological targets that are most likely to respond to new therapies. Partners in this initiative, which include major drug makers such as GlaxoSmithKline and Merck, along with nonprofits such as the Rheumatology Research Foundation, the Lupus Foundation of America, the American Diabetes Association, and the Alzheimer’s Association, are expected to invest more than $230 million over 5 years in the first projects, which will focus on rheumatoid arthritis and systemic lupus erythematosus (total funding of $41.6 million), type 2 diabetes ($58.4 million), and Alzheimer’s disease ($129.5 million).

Data and analyses generated by these projects will be made publicly available to the broad biomedical community through an Internet-based information portal, and the initial projects could set the stage for broadening the initiative into other diseases and conditions, the NIH says.

For rheumatoid arthritis and lupus, the project will focus on collecting and analyzing tissue and blood samples from patients to see how changes at the single-cell and systems levels can provide insight into the disease process and inform comparisons across diseases, as well as identify differences between patients in response to treatment.

The type 2 diabetes project will aim "to use and supplement the substantial amount of human genetic data available from people with type 2 diabetes – or at risk for developing type 2 diabetes – to identify and validate novel molecules and pathways as targets for therapeutic development." Researchers also will build a type 2 diabetes knowledge portal for academic and industry researchers that will contain DNA sequences, functional genomic and epigenomic information, and clinical data from studies on type 2 diabetes and its cardiac and renal complications totaling 100,000-150,000 individuals.

The Alzheimer’s project will seek to increase the amount of data available from clinical trials to increase support for therapeutic target validation in humans. This will be done by using selected biomarkers in four NIH- and industry-supported clinical trials that are designed to delay or prevent disease onset, as well as performing a large-scale analysis of brain tissue samples from Alzheimer’s disease patients to validate biological targets previously shown to play key roles in disease progression and increase understanding of the molecular pathways involved in the disease, in order to identify new potential therapeutic targets.

jevans@frontlinemedcom.com

The National Institutes of Health, 10 biopharmaceutical companies, and several nonprofit organizations have partnered to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development.

The Accelerating Medicines Partnership aims to pinpoint biological targets that are most likely to respond to new therapies. Partners in this initiative, which include major drug makers such as GlaxoSmithKline and Merck, along with nonprofits such as the Rheumatology Research Foundation, the Lupus Foundation of America, the American Diabetes Association, and the Alzheimer’s Association, are expected to invest more than $230 million over 5 years in the first projects, which will focus on rheumatoid arthritis and systemic lupus erythematosus (total funding of $41.6 million), type 2 diabetes ($58.4 million), and Alzheimer’s disease ($129.5 million).

Data and analyses generated by these projects will be made publicly available to the broad biomedical community through an Internet-based information portal, and the initial projects could set the stage for broadening the initiative into other diseases and conditions, the NIH says.

For rheumatoid arthritis and lupus, the project will focus on collecting and analyzing tissue and blood samples from patients to see how changes at the single-cell and systems levels can provide insight into the disease process and inform comparisons across diseases, as well as identify differences between patients in response to treatment.

The type 2 diabetes project will aim "to use and supplement the substantial amount of human genetic data available from people with type 2 diabetes – or at risk for developing type 2 diabetes – to identify and validate novel molecules and pathways as targets for therapeutic development." Researchers also will build a type 2 diabetes knowledge portal for academic and industry researchers that will contain DNA sequences, functional genomic and epigenomic information, and clinical data from studies on type 2 diabetes and its cardiac and renal complications totaling 100,000-150,000 individuals.

The Alzheimer’s project will seek to increase the amount of data available from clinical trials to increase support for therapeutic target validation in humans. This will be done by using selected biomarkers in four NIH- and industry-supported clinical trials that are designed to delay or prevent disease onset, as well as performing a large-scale analysis of brain tissue samples from Alzheimer’s disease patients to validate biological targets previously shown to play key roles in disease progression and increase understanding of the molecular pathways involved in the disease, in order to identify new potential therapeutic targets.

jevans@frontlinemedcom.com

The National Institutes of Health, 10 biopharmaceutical companies, and several nonprofit organizations have partnered to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development.

The Accelerating Medicines Partnership aims to pinpoint biological targets that are most likely to respond to new therapies. Partners in this initiative, which include major drug makers such as GlaxoSmithKline and Merck, along with nonprofits such as the Rheumatology Research Foundation, the Lupus Foundation of America, the American Diabetes Association, and the Alzheimer’s Association, are expected to invest more than $230 million over 5 years in the first projects, which will focus on rheumatoid arthritis and systemic lupus erythematosus (total funding of $41.6 million), type 2 diabetes ($58.4 million), and Alzheimer’s disease ($129.5 million).

Data and analyses generated by these projects will be made publicly available to the broad biomedical community through an Internet-based information portal, and the initial projects could set the stage for broadening the initiative into other diseases and conditions, the NIH says.

For rheumatoid arthritis and lupus, the project will focus on collecting and analyzing tissue and blood samples from patients to see how changes at the single-cell and systems levels can provide insight into the disease process and inform comparisons across diseases, as well as identify differences between patients in response to treatment.

The type 2 diabetes project will aim "to use and supplement the substantial amount of human genetic data available from people with type 2 diabetes – or at risk for developing type 2 diabetes – to identify and validate novel molecules and pathways as targets for therapeutic development." Researchers also will build a type 2 diabetes knowledge portal for academic and industry researchers that will contain DNA sequences, functional genomic and epigenomic information, and clinical data from studies on type 2 diabetes and its cardiac and renal complications totaling 100,000-150,000 individuals.

The Alzheimer’s project will seek to increase the amount of data available from clinical trials to increase support for therapeutic target validation in humans. This will be done by using selected biomarkers in four NIH- and industry-supported clinical trials that are designed to delay or prevent disease onset, as well as performing a large-scale analysis of brain tissue samples from Alzheimer’s disease patients to validate biological targets previously shown to play key roles in disease progression and increase understanding of the molecular pathways involved in the disease, in order to identify new potential therapeutic targets.

jevans@frontlinemedcom.com