Rheumatoid Arthritis

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON– In the search for safer alternatives to glucocorticoid therapy, DAGR (PF-0417327) may prove to be a contender. The investigational drug is a selective, high-affinity, dissociated agonist of the glucocorticoid receptor, and appeared to be associated with fewer potential adverse events than are typically seen with glucocorticoids in a phase II trial that compared 8 weeks of the drug against placebo and prednisone.

The findings suggest that DAGR is therapeutically equivalent to prednisone 10 mg once daily, but with side effects comparable with those seen with prednisone 5 mg once daily and with no clinical symptoms of adrenal insufficiency. Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant in Portola Valley, Calif., presented data on the drug during the late-breaker session and discussed the implications of the findings at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON – A multidisciplinary clinic of rheumatologists and cardiologists at the Mayo Clinic in Rochester, Minn., is focused on spreading awareness of cardiovascular disease in patients with rheumatic diseases and finding the best ways to prevent it.

The Cardio-Rheumatology Clinic, which was formed in 2013, is one of a growing number of clinics around the world that have started since the first Preventive Cardio-Rheuma Clinic opened at Diakonhjemmet Hospital in Oslo. Two of the founders of the Mayo Clinic’s Cardio-Rheumatology Clinic, Dr. Sharon L. Mulvagh and Dr. Sherine Gabriel, talk about its origins, goals, and vision in a video discussion at the annual meeting of the American College of Rheumatology.

jevans@frontlinemedcom.com

BOSTON – A multidisciplinary clinic of rheumatologists and cardiologists at the Mayo Clinic in Rochester, Minn., is focused on spreading awareness of cardiovascular disease in patients with rheumatic diseases and finding the best ways to prevent it.

The Cardio-Rheumatology Clinic, which was formed in 2013, is one of a growing number of clinics around the world that have started since the first Preventive Cardio-Rheuma Clinic opened at Diakonhjemmet Hospital in Oslo. Two of the founders of the Mayo Clinic’s Cardio-Rheumatology Clinic, Dr. Sharon L. Mulvagh and Dr. Sherine Gabriel, talk about its origins, goals, and vision in a video discussion at the annual meeting of the American College of Rheumatology.

jevans@frontlinemedcom.com

BOSTON – A multidisciplinary clinic of rheumatologists and cardiologists at the Mayo Clinic in Rochester, Minn., is focused on spreading awareness of cardiovascular disease in patients with rheumatic diseases and finding the best ways to prevent it.

The Cardio-Rheumatology Clinic, which was formed in 2013, is one of a growing number of clinics around the world that have started since the first Preventive Cardio-Rheuma Clinic opened at Diakonhjemmet Hospital in Oslo. Two of the founders of the Mayo Clinic’s Cardio-Rheumatology Clinic, Dr. Sharon L. Mulvagh and Dr. Sherine Gabriel, talk about its origins, goals, and vision in a video discussion at the annual meeting of the American College of Rheumatology.

jevans@frontlinemedcom.com

BOSTON – Rheumatoid arthritis patients taking tumor necrosis factor inhibitors ran a lower risk of developing congestive heart failure than did those on nonbiologic disease-modifying antirheumatic drugs, based on data from a large British registry.

Dr. Alper van Sijl of the University of Manchester (England) reported that, among comparable RA patients who have not yet developed CHF, fully adjusted propensity scores showed a reduced risk for developing CHF in those taking TNF inhibitors. He explained the possible reasons for the findings and described next steps in new studies designed to cut the risk of CHF in RA patients during an interview at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON – Rheumatoid arthritis patients taking tumor necrosis factor inhibitors ran a lower risk of developing congestive heart failure than did those on nonbiologic disease-modifying antirheumatic drugs, based on data from a large British registry.

Dr. Alper van Sijl of the University of Manchester (England) reported that, among comparable RA patients who have not yet developed CHF, fully adjusted propensity scores showed a reduced risk for developing CHF in those taking TNF inhibitors. He explained the possible reasons for the findings and described next steps in new studies designed to cut the risk of CHF in RA patients during an interview at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON – Rheumatoid arthritis patients taking tumor necrosis factor inhibitors ran a lower risk of developing congestive heart failure than did those on nonbiologic disease-modifying antirheumatic drugs, based on data from a large British registry.

Dr. Alper van Sijl of the University of Manchester (England) reported that, among comparable RA patients who have not yet developed CHF, fully adjusted propensity scores showed a reduced risk for developing CHF in those taking TNF inhibitors. He explained the possible reasons for the findings and described next steps in new studies designed to cut the risk of CHF in RA patients during an interview at the annual meeting of the American College of Rheumatology.

mdales@frontlinemedcom.com

BOSTON– The herpes zoster vaccine may be safe to give to patients who are taking biologic therapies and have quiescent rheumatologic disorders, based on preliminary data from two studies presented at the annual meeting of the American College of Rheumatology.

Dr. Jeffrey Curtis of the University of Alabama at Birmingham presented data about the extent of the increased risk for herpes zoster in rheumatology patients, especially those with systemic lupus erythematosus, and some intriguing results on 630 patients on biologic therapies who inadvertently got the vaccine.

Dr. Stephen Lindsey of Ochsner Health System in Baton Rouge, La., said that he continues to evolve a protocol for herpes zoster vaccination of his patients with rheumatologic disorders.

In our exclusive interview at ACR14, the two researchers discussed the implications of their separate studies on the subject and revealed the next steps of a prospective study of herpes zoster vaccination in patients with rheumatologic disorders that is just getting underway.

mdales@frontlinemedcom.com

BOSTON– The herpes zoster vaccine may be safe to give to patients who are taking biologic therapies and have quiescent rheumatologic disorders, based on preliminary data from two studies presented at the annual meeting of the American College of Rheumatology.

Dr. Jeffrey Curtis of the University of Alabama at Birmingham presented data about the extent of the increased risk for herpes zoster in rheumatology patients, especially those with systemic lupus erythematosus, and some intriguing results on 630 patients on biologic therapies who inadvertently got the vaccine.

Dr. Stephen Lindsey of Ochsner Health System in Baton Rouge, La., said that he continues to evolve a protocol for herpes zoster vaccination of his patients with rheumatologic disorders.

In our exclusive interview at ACR14, the two researchers discussed the implications of their separate studies on the subject and revealed the next steps of a prospective study of herpes zoster vaccination in patients with rheumatologic disorders that is just getting underway.

mdales@frontlinemedcom.com

BOSTON– The herpes zoster vaccine may be safe to give to patients who are taking biologic therapies and have quiescent rheumatologic disorders, based on preliminary data from two studies presented at the annual meeting of the American College of Rheumatology.

Dr. Jeffrey Curtis of the University of Alabama at Birmingham presented data about the extent of the increased risk for herpes zoster in rheumatology patients, especially those with systemic lupus erythematosus, and some intriguing results on 630 patients on biologic therapies who inadvertently got the vaccine.

Dr. Stephen Lindsey of Ochsner Health System in Baton Rouge, La., said that he continues to evolve a protocol for herpes zoster vaccination of his patients with rheumatologic disorders.

In our exclusive interview at ACR14, the two researchers discussed the implications of their separate studies on the subject and revealed the next steps of a prospective study of herpes zoster vaccination in patients with rheumatologic disorders that is just getting underway.

mdales@frontlinemedcom.com

BOSTON – A diagnosis of rheumatoid arthritis doubled the risk of death from any cause over the risk for those without RA, based on 34 years of follow-up data from women in the Nurses’ Health Study.

Incident RA was associated with a 40% increase in the risk of death, and seropositive RA was associated with a 51% increase in the risk of death, Dr. Jeffrey A. Sparks of Brigham and Women’s Hospital, Boston, reported at the annual meeting of the American College of Rheumatology.

The data also revealed a much stronger link between RA and the risk of death due to respiratory causes. That rate was sixfold higher in seropositive women with RA. While there is an appreciation of an increased risk for cardiovascular disease and cancer in RA patients, deaths due to respiratory disease are “an underappreciated cause of death” that warrant more focus in these patients, he said.

Among the 25,699 deaths that took place during the course of the study, 261 of them occurred in the 960 women who developed RA after they enrolled in the study. Among the women with RA, cancer was the cause of death in 29%, cardiovascular disease in 22%, and respiratory causes in 16%.

The study allows direct comparisons of RA patients and controls over a prolonged time with detailed data on clinical, lifestyle, and serologic factors, he said. Compared with women without RA, all-cause mortality was significantly higher in women with RA after adjustment for age and other potentially confounding factors (hazard ratio, 2.07; 95% CI, 1.83-2.35).

The variables used to adjust the analyses were age, questionnaire period, U.S. region, race/ethnicity, education, husband’s education, body mass index (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m2), cigarette smoking pack-years (never, 0-10, 10.1-20, >20), postmenopausal hormone use, physical activity, healthy eating index, cancer, cardiovascular disease, diabetes, family history of diabetes, family history of cancer, family history of myocardial infarction before age 60 years, and aspirin use. Modifiable factors were adjusted up to RA diagnosis (cigarette smoking pack-years, physical activity, and BMI).

The mortality rate was higher for women with seropositive disease than it was for those without RA (HR, 2.33; 95% CI, 2.00-2.71), as was the rate for seronegative RA (HR, 1.60; 95% CI, 1.30-1.98).

For every 5 years of RA duration, mortality risk increased 32% (95% CI, 27%-36%) compared with unaffected women. Women with RA had significantly increased risks for mortality from CVD (HR, 1.87; 95% CI, 1.44-2.43), cancer (HR, 1.35; 95% CI, 1.07-1.69), and respiratory causes (HR, 4.50; 95% CI, 3.28-6.17), compared with women without the disease.

Respiratory mortality for women with seropositive RA was sixfold higher than it was for non-RA women (HR, 6.23; 95% CI, 4.38-8.85). Among women with RA, there were 43 respiratory deaths caused by pneumonia (11), emphysema (8), chronic interstitial lung disease (5), asthma (1), and other respiratory diseases (18).

Dr. Sparks had no relevant financial disclosures. The National Institutes of Health and the Rheumatology Research Foundation funded the study. 

mdales@frontlinemedcom.com

BOSTON – A diagnosis of rheumatoid arthritis doubled the risk of death from any cause over the risk for those without RA, based on 34 years of follow-up data from women in the Nurses’ Health Study.

Incident RA was associated with a 40% increase in the risk of death, and seropositive RA was associated with a 51% increase in the risk of death, Dr. Jeffrey A. Sparks of Brigham and Women’s Hospital, Boston, reported at the annual meeting of the American College of Rheumatology.

The data also revealed a much stronger link between RA and the risk of death due to respiratory causes. That rate was sixfold higher in seropositive women with RA. While there is an appreciation of an increased risk for cardiovascular disease and cancer in RA patients, deaths due to respiratory disease are “an underappreciated cause of death” that warrant more focus in these patients, he said.

Among the 25,699 deaths that took place during the course of the study, 261 of them occurred in the 960 women who developed RA after they enrolled in the study. Among the women with RA, cancer was the cause of death in 29%, cardiovascular disease in 22%, and respiratory causes in 16%.

The study allows direct comparisons of RA patients and controls over a prolonged time with detailed data on clinical, lifestyle, and serologic factors, he said. Compared with women without RA, all-cause mortality was significantly higher in women with RA after adjustment for age and other potentially confounding factors (hazard ratio, 2.07; 95% CI, 1.83-2.35).

The variables used to adjust the analyses were age, questionnaire period, U.S. region, race/ethnicity, education, husband’s education, body mass index (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m2), cigarette smoking pack-years (never, 0-10, 10.1-20, >20), postmenopausal hormone use, physical activity, healthy eating index, cancer, cardiovascular disease, diabetes, family history of diabetes, family history of cancer, family history of myocardial infarction before age 60 years, and aspirin use. Modifiable factors were adjusted up to RA diagnosis (cigarette smoking pack-years, physical activity, and BMI).

The mortality rate was higher for women with seropositive disease than it was for those without RA (HR, 2.33; 95% CI, 2.00-2.71), as was the rate for seronegative RA (HR, 1.60; 95% CI, 1.30-1.98).

For every 5 years of RA duration, mortality risk increased 32% (95% CI, 27%-36%) compared with unaffected women. Women with RA had significantly increased risks for mortality from CVD (HR, 1.87; 95% CI, 1.44-2.43), cancer (HR, 1.35; 95% CI, 1.07-1.69), and respiratory causes (HR, 4.50; 95% CI, 3.28-6.17), compared with women without the disease.

Respiratory mortality for women with seropositive RA was sixfold higher than it was for non-RA women (HR, 6.23; 95% CI, 4.38-8.85). Among women with RA, there were 43 respiratory deaths caused by pneumonia (11), emphysema (8), chronic interstitial lung disease (5), asthma (1), and other respiratory diseases (18).

Dr. Sparks had no relevant financial disclosures. The National Institutes of Health and the Rheumatology Research Foundation funded the study. 

mdales@frontlinemedcom.com

BOSTON – A diagnosis of rheumatoid arthritis doubled the risk of death from any cause over the risk for those without RA, based on 34 years of follow-up data from women in the Nurses’ Health Study.

Incident RA was associated with a 40% increase in the risk of death, and seropositive RA was associated with a 51% increase in the risk of death, Dr. Jeffrey A. Sparks of Brigham and Women’s Hospital, Boston, reported at the annual meeting of the American College of Rheumatology.

The data also revealed a much stronger link between RA and the risk of death due to respiratory causes. That rate was sixfold higher in seropositive women with RA. While there is an appreciation of an increased risk for cardiovascular disease and cancer in RA patients, deaths due to respiratory disease are “an underappreciated cause of death” that warrant more focus in these patients, he said.

Among the 25,699 deaths that took place during the course of the study, 261 of them occurred in the 960 women who developed RA after they enrolled in the study. Among the women with RA, cancer was the cause of death in 29%, cardiovascular disease in 22%, and respiratory causes in 16%.

The study allows direct comparisons of RA patients and controls over a prolonged time with detailed data on clinical, lifestyle, and serologic factors, he said. Compared with women without RA, all-cause mortality was significantly higher in women with RA after adjustment for age and other potentially confounding factors (hazard ratio, 2.07; 95% CI, 1.83-2.35).

The variables used to adjust the analyses were age, questionnaire period, U.S. region, race/ethnicity, education, husband’s education, body mass index (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m2), cigarette smoking pack-years (never, 0-10, 10.1-20, >20), postmenopausal hormone use, physical activity, healthy eating index, cancer, cardiovascular disease, diabetes, family history of diabetes, family history of cancer, family history of myocardial infarction before age 60 years, and aspirin use. Modifiable factors were adjusted up to RA diagnosis (cigarette smoking pack-years, physical activity, and BMI).

The mortality rate was higher for women with seropositive disease than it was for those without RA (HR, 2.33; 95% CI, 2.00-2.71), as was the rate for seronegative RA (HR, 1.60; 95% CI, 1.30-1.98).

For every 5 years of RA duration, mortality risk increased 32% (95% CI, 27%-36%) compared with unaffected women. Women with RA had significantly increased risks for mortality from CVD (HR, 1.87; 95% CI, 1.44-2.43), cancer (HR, 1.35; 95% CI, 1.07-1.69), and respiratory causes (HR, 4.50; 95% CI, 3.28-6.17), compared with women without the disease.

Respiratory mortality for women with seropositive RA was sixfold higher than it was for non-RA women (HR, 6.23; 95% CI, 4.38-8.85). Among women with RA, there were 43 respiratory deaths caused by pneumonia (11), emphysema (8), chronic interstitial lung disease (5), asthma (1), and other respiratory diseases (18).

Dr. Sparks had no relevant financial disclosures. The National Institutes of Health and the Rheumatology Research Foundation funded the study. 

mdales@frontlinemedcom.com

BOSTON – Aggressive treatment of rheumatoid arthritis patients aimed at achieving Disease Activity Scores of 2.4 or less was associated with mortality rates that were not significantly different from those seen in the general population, based on the results of a 10-year Dutch study.

Irrespective of the treatment regimen, keeping the DAS (Disease Activity Score) at 2.4 or below is associated with lower inflammation, according to Dr. Iris Markusse of Leiden University Medical Center. “Historically, mortality risk in RA was significantly increased when inflammation was not as effectively suppressed ... [but with intensified treatment] inflammation can be so well controlled that it no longer affects overall survival.”

In the Behandel Strategieen (BeST) study, 508 patients with recent active-onset RA were randomized to one of four treatment approaches. Patients received either sequential monotherapy with methotrexate, step-up therapy with methotrexate, methotrexate plus sulfasalazine and prednisone, or methotrexate and infliximab. For all patients, the treatment target was a DAS of 2.4 or less, and follow-up occurred at 3-month intervals.

Patients who started on methotrexate monotherapy and had a DAS exceeding 2.4 received the next step in therapy, which included adding or switching to other therapies as needed. Conversely, if low disease activity was seen for at least 6 consecutive months, combination therapy was tapered to maintenance monotherapy. After the third year of the trial, patients who had at least 6 consecutive months on maintenance monotherapy had to stop that drug as well.

Over the course of the study, 80% of participants had low disease activity, 45% were in remission, and 15% were in drug-free remission, she reported at a press conference during the annual meeting of the American College of Rheumatology.

Of the 508 patients, 72 died at a mean age of 75 years; the deaths occurred in 16 of 126 patients on methotrexate monotherapy, 15 of 121 on step-up methotrexate, 21 of 133 on methotrexate plus sulfasalazine and prednisone, and 20 of 128 on methotrexate and infliximab. Based on the general Dutch population, 62 deaths would have been expected.

While mortality risk was not significantly different among the treatment arms; mortality risk was higher for patients who were older at baseline, male, smokers, and those with poorer scores on a baseline health assessment questionnaire. The most significant risk factor was smoking at baseline (hazard ratio, 5.19; 95% confidence interval, 3.08-8.75).

Encouraging patients to quit smoking might be effective for reducing mortality, she added.

Dr. Markusse declared having no relevant financial disclosures. Funding for the study included a government grant from the Dutch College of Health Insurance Companies, with additional funding from Schering-Plough/MSD and Centocor/Janssen.

mdales@frontlinemedcom.com

BOSTON – Aggressive treatment of rheumatoid arthritis patients aimed at achieving Disease Activity Scores of 2.4 or less was associated with mortality rates that were not significantly different from those seen in the general population, based on the results of a 10-year Dutch study.

Irrespective of the treatment regimen, keeping the DAS (Disease Activity Score) at 2.4 or below is associated with lower inflammation, according to Dr. Iris Markusse of Leiden University Medical Center. “Historically, mortality risk in RA was significantly increased when inflammation was not as effectively suppressed ... [but with intensified treatment] inflammation can be so well controlled that it no longer affects overall survival.”

In the Behandel Strategieen (BeST) study, 508 patients with recent active-onset RA were randomized to one of four treatment approaches. Patients received either sequential monotherapy with methotrexate, step-up therapy with methotrexate, methotrexate plus sulfasalazine and prednisone, or methotrexate and infliximab. For all patients, the treatment target was a DAS of 2.4 or less, and follow-up occurred at 3-month intervals.

Patients who started on methotrexate monotherapy and had a DAS exceeding 2.4 received the next step in therapy, which included adding or switching to other therapies as needed. Conversely, if low disease activity was seen for at least 6 consecutive months, combination therapy was tapered to maintenance monotherapy. After the third year of the trial, patients who had at least 6 consecutive months on maintenance monotherapy had to stop that drug as well.

Over the course of the study, 80% of participants had low disease activity, 45% were in remission, and 15% were in drug-free remission, she reported at a press conference during the annual meeting of the American College of Rheumatology.

Of the 508 patients, 72 died at a mean age of 75 years; the deaths occurred in 16 of 126 patients on methotrexate monotherapy, 15 of 121 on step-up methotrexate, 21 of 133 on methotrexate plus sulfasalazine and prednisone, and 20 of 128 on methotrexate and infliximab. Based on the general Dutch population, 62 deaths would have been expected.

While mortality risk was not significantly different among the treatment arms; mortality risk was higher for patients who were older at baseline, male, smokers, and those with poorer scores on a baseline health assessment questionnaire. The most significant risk factor was smoking at baseline (hazard ratio, 5.19; 95% confidence interval, 3.08-8.75).

Encouraging patients to quit smoking might be effective for reducing mortality, she added.

Dr. Markusse declared having no relevant financial disclosures. Funding for the study included a government grant from the Dutch College of Health Insurance Companies, with additional funding from Schering-Plough/MSD and Centocor/Janssen.

mdales@frontlinemedcom.com

BOSTON – Aggressive treatment of rheumatoid arthritis patients aimed at achieving Disease Activity Scores of 2.4 or less was associated with mortality rates that were not significantly different from those seen in the general population, based on the results of a 10-year Dutch study.

Irrespective of the treatment regimen, keeping the DAS (Disease Activity Score) at 2.4 or below is associated with lower inflammation, according to Dr. Iris Markusse of Leiden University Medical Center. “Historically, mortality risk in RA was significantly increased when inflammation was not as effectively suppressed ... [but with intensified treatment] inflammation can be so well controlled that it no longer affects overall survival.”

In the Behandel Strategieen (BeST) study, 508 patients with recent active-onset RA were randomized to one of four treatment approaches. Patients received either sequential monotherapy with methotrexate, step-up therapy with methotrexate, methotrexate plus sulfasalazine and prednisone, or methotrexate and infliximab. For all patients, the treatment target was a DAS of 2.4 or less, and follow-up occurred at 3-month intervals.

Patients who started on methotrexate monotherapy and had a DAS exceeding 2.4 received the next step in therapy, which included adding or switching to other therapies as needed. Conversely, if low disease activity was seen for at least 6 consecutive months, combination therapy was tapered to maintenance monotherapy. After the third year of the trial, patients who had at least 6 consecutive months on maintenance monotherapy had to stop that drug as well.

Over the course of the study, 80% of participants had low disease activity, 45% were in remission, and 15% were in drug-free remission, she reported at a press conference during the annual meeting of the American College of Rheumatology.

Of the 508 patients, 72 died at a mean age of 75 years; the deaths occurred in 16 of 126 patients on methotrexate monotherapy, 15 of 121 on step-up methotrexate, 21 of 133 on methotrexate plus sulfasalazine and prednisone, and 20 of 128 on methotrexate and infliximab. Based on the general Dutch population, 62 deaths would have been expected.

While mortality risk was not significantly different among the treatment arms; mortality risk was higher for patients who were older at baseline, male, smokers, and those with poorer scores on a baseline health assessment questionnaire. The most significant risk factor was smoking at baseline (hazard ratio, 5.19; 95% confidence interval, 3.08-8.75).

Encouraging patients to quit smoking might be effective for reducing mortality, she added.

Dr. Markusse declared having no relevant financial disclosures. Funding for the study included a government grant from the Dutch College of Health Insurance Companies, with additional funding from Schering-Plough/MSD and Centocor/Janssen.

mdales@frontlinemedcom.com

BOSTON– A bundle of eight measures was effective in improving the quality of rheumatoid arthritis care while reducing costs, Dr. Eric D. Newman reported at the annual meeting of the American College of Rheumatology.

At the start of the program, 22% of roughly 2,400 RA patients had achieved all of the applicable quality measures that were integrated into the program. After 22 months in the program, 40% had met all of the measures.

Using routine disease measures, the program was successful for de-escalating use of biologics among the patients. After 1 year, the associated savings came to $720,000; a savings estimate of $1.2 million is projected for 2014.

“We recognized the importance of objectively and routinely measuring disease activity, and using that information to engage our patients and drive a new systematic strategic approach to rheumatoid arthritis care,” said Dr. Newman, director of rheumatology for the Geisinger Health System, Wilkes-Barre, Penn., and the program’s designer.

The AIM FARTHER (Attribution, Integration, Measurement, Finances and Reporting of Therapies) model was designed and implemented for about 2,400 RA patients cared for by the 17 rheumatologists within the Geisinger Health System. The eight measures included disease activity measures (RA on DMARD, active RA on DMARD, RA with CDAI [Clinical Disease Activity Index], and RA at low disease activity); drug safety measures (TB testing if on a biologic agent, yearly influenza vaccination, and pneumococcal vaccination), and a comorbidity measure (check of LDL cholesterol).

Individual patient scorecards were developed via patient responses on a touch-screen questionnaire and input from physicians, nurses, and the electronic health record. The data were used to measure RA patient care gaps to be resolved. The measures were shared and analyzed to close care gaps as well as create provider and department performance reports.

Before the start of the program, measures were high for the percentage of RA patients and the percentage of patients with active RA on a DMARD as well as the percentage of patients who had their LDLs checked. As a result, only modest further improvements were seen after 22 months of the program (from 88% at baseline to 90% for the percentage of RA patients on a DMARD, from 92% to 93% for RA patients with active disease on a DMARD, and from 93% to 95 for LDL checks).

Significant improvements in other measures were seen, however, including a rise in the use of CDAI measures from 52% to 84%, a rise in TB testing for those on a biologic from 83% to 93%, an increase in yearly influenza vaccination from 59% to 75%, and a rise in pneumococcal vaccination from 59% to 72%.

As a care model, AIM FARTHER seeks to employ provider engagement, process redesign, measurement, and information technology, Dr. Newman said. The components of the program include establishing a registry, defining roles and attribution, integrating primary and specialty care, defining a strategic approach to RA care, developing an RA quality measure bundle, task management and performance reporting, and a financial incentive model.

The success of AIM FARTHER “is not due to any one individual, but [relies on] meaningful involvement of all members of the rheumatology team, holding ourselves accountable, dedicating the time needed to perform the work, and creating an internal forum to discuss quality improvement on a regular basis. This approach moved our rheumatology team from engagement to buy-in to ownership. The result is an RA population management program that is sustainable yet evolving, as we challenge ourselves to continuously improve the quality of care for our patients with rheumatic disease,” Dr. Newman said.

The authors had no disclosures. The work was internally funded by the Geisinger Health System.

mdales@frontlinemedcom.com

BOSTON– A bundle of eight measures was effective in improving the quality of rheumatoid arthritis care while reducing costs, Dr. Eric D. Newman reported at the annual meeting of the American College of Rheumatology.

At the start of the program, 22% of roughly 2,400 RA patients had achieved all of the applicable quality measures that were integrated into the program. After 22 months in the program, 40% had met all of the measures.

Using routine disease measures, the program was successful for de-escalating use of biologics among the patients. After 1 year, the associated savings came to $720,000; a savings estimate of $1.2 million is projected for 2014.

“We recognized the importance of objectively and routinely measuring disease activity, and using that information to engage our patients and drive a new systematic strategic approach to rheumatoid arthritis care,” said Dr. Newman, director of rheumatology for the Geisinger Health System, Wilkes-Barre, Penn., and the program’s designer.

The AIM FARTHER (Attribution, Integration, Measurement, Finances and Reporting of Therapies) model was designed and implemented for about 2,400 RA patients cared for by the 17 rheumatologists within the Geisinger Health System. The eight measures included disease activity measures (RA on DMARD, active RA on DMARD, RA with CDAI [Clinical Disease Activity Index], and RA at low disease activity); drug safety measures (TB testing if on a biologic agent, yearly influenza vaccination, and pneumococcal vaccination), and a comorbidity measure (check of LDL cholesterol).

Individual patient scorecards were developed via patient responses on a touch-screen questionnaire and input from physicians, nurses, and the electronic health record. The data were used to measure RA patient care gaps to be resolved. The measures were shared and analyzed to close care gaps as well as create provider and department performance reports.

Before the start of the program, measures were high for the percentage of RA patients and the percentage of patients with active RA on a DMARD as well as the percentage of patients who had their LDLs checked. As a result, only modest further improvements were seen after 22 months of the program (from 88% at baseline to 90% for the percentage of RA patients on a DMARD, from 92% to 93% for RA patients with active disease on a DMARD, and from 93% to 95 for LDL checks).

Significant improvements in other measures were seen, however, including a rise in the use of CDAI measures from 52% to 84%, a rise in TB testing for those on a biologic from 83% to 93%, an increase in yearly influenza vaccination from 59% to 75%, and a rise in pneumococcal vaccination from 59% to 72%.

As a care model, AIM FARTHER seeks to employ provider engagement, process redesign, measurement, and information technology, Dr. Newman said. The components of the program include establishing a registry, defining roles and attribution, integrating primary and specialty care, defining a strategic approach to RA care, developing an RA quality measure bundle, task management and performance reporting, and a financial incentive model.

The success of AIM FARTHER “is not due to any one individual, but [relies on] meaningful involvement of all members of the rheumatology team, holding ourselves accountable, dedicating the time needed to perform the work, and creating an internal forum to discuss quality improvement on a regular basis. This approach moved our rheumatology team from engagement to buy-in to ownership. The result is an RA population management program that is sustainable yet evolving, as we challenge ourselves to continuously improve the quality of care for our patients with rheumatic disease,” Dr. Newman said.

The authors had no disclosures. The work was internally funded by the Geisinger Health System.

mdales@frontlinemedcom.com

BOSTON– A bundle of eight measures was effective in improving the quality of rheumatoid arthritis care while reducing costs, Dr. Eric D. Newman reported at the annual meeting of the American College of Rheumatology.

At the start of the program, 22% of roughly 2,400 RA patients had achieved all of the applicable quality measures that were integrated into the program. After 22 months in the program, 40% had met all of the measures.

Using routine disease measures, the program was successful for de-escalating use of biologics among the patients. After 1 year, the associated savings came to $720,000; a savings estimate of $1.2 million is projected for 2014.

“We recognized the importance of objectively and routinely measuring disease activity, and using that information to engage our patients and drive a new systematic strategic approach to rheumatoid arthritis care,” said Dr. Newman, director of rheumatology for the Geisinger Health System, Wilkes-Barre, Penn., and the program’s designer.

The AIM FARTHER (Attribution, Integration, Measurement, Finances and Reporting of Therapies) model was designed and implemented for about 2,400 RA patients cared for by the 17 rheumatologists within the Geisinger Health System. The eight measures included disease activity measures (RA on DMARD, active RA on DMARD, RA with CDAI [Clinical Disease Activity Index], and RA at low disease activity); drug safety measures (TB testing if on a biologic agent, yearly influenza vaccination, and pneumococcal vaccination), and a comorbidity measure (check of LDL cholesterol).

Individual patient scorecards were developed via patient responses on a touch-screen questionnaire and input from physicians, nurses, and the electronic health record. The data were used to measure RA patient care gaps to be resolved. The measures were shared and analyzed to close care gaps as well as create provider and department performance reports.

Before the start of the program, measures were high for the percentage of RA patients and the percentage of patients with active RA on a DMARD as well as the percentage of patients who had their LDLs checked. As a result, only modest further improvements were seen after 22 months of the program (from 88% at baseline to 90% for the percentage of RA patients on a DMARD, from 92% to 93% for RA patients with active disease on a DMARD, and from 93% to 95 for LDL checks).

Significant improvements in other measures were seen, however, including a rise in the use of CDAI measures from 52% to 84%, a rise in TB testing for those on a biologic from 83% to 93%, an increase in yearly influenza vaccination from 59% to 75%, and a rise in pneumococcal vaccination from 59% to 72%.

As a care model, AIM FARTHER seeks to employ provider engagement, process redesign, measurement, and information technology, Dr. Newman said. The components of the program include establishing a registry, defining roles and attribution, integrating primary and specialty care, defining a strategic approach to RA care, developing an RA quality measure bundle, task management and performance reporting, and a financial incentive model.

The success of AIM FARTHER “is not due to any one individual, but [relies on] meaningful involvement of all members of the rheumatology team, holding ourselves accountable, dedicating the time needed to perform the work, and creating an internal forum to discuss quality improvement on a regular basis. This approach moved our rheumatology team from engagement to buy-in to ownership. The result is an RA population management program that is sustainable yet evolving, as we challenge ourselves to continuously improve the quality of care for our patients with rheumatic disease,” Dr. Newman said.

The authors had no disclosures. The work was internally funded by the Geisinger Health System.

mdales@frontlinemedcom.com

BOSTON - With follow up every 3 months, the survival rates of RA patients were comparable to those of the general population in a 10-year study of patients in the Netherlands. Dr. Iris Markusse of Leiden University Medical Center credits regimens that were tailored to keep the Disease Activity Score at levels of 2.4 or lower. Further, the medications used in this strategy did not increase patient mortality. Dr. Markusse discusses the findings of BeST in an exclusive interview at the annual meeting of the American College of Rheumatology.

BOSTON - With follow up every 3 months, the survival rates of RA patients were comparable to those of the general population in a 10-year study of patients in the Netherlands. Dr. Iris Markusse of Leiden University Medical Center credits regimens that were tailored to keep the Disease Activity Score at levels of 2.4 or lower. Further, the medications used in this strategy did not increase patient mortality. Dr. Markusse discusses the findings of BeST in an exclusive interview at the annual meeting of the American College of Rheumatology.

BOSTON - With follow up every 3 months, the survival rates of RA patients were comparable to those of the general population in a 10-year study of patients in the Netherlands. Dr. Iris Markusse of Leiden University Medical Center credits regimens that were tailored to keep the Disease Activity Score at levels of 2.4 or lower. Further, the medications used in this strategy did not increase patient mortality. Dr. Markusse discusses the findings of BeST in an exclusive interview at the annual meeting of the American College of Rheumatology.