Rheumatoid Arthritis

LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.

“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.

The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.

“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.

The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.

In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.

For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”

There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV₁), there was no signal of benefit for those with severe, moderate, or mild impairment.

One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV₁ were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.

He concluded that there was no signal of benefit even among those with the greatest expression of the target.

“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.

Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.

LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.

“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.

The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.

“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.

The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.

In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.

For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”

There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV₁), there was no signal of benefit for those with severe, moderate, or mild impairment.

One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV₁ were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.

He concluded that there was no signal of benefit even among those with the greatest expression of the target.

“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.

Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.

LONDON – Despite very promising activity in animal models of idiopathic pulmonary fibrosis (IPF), a monoclonal antibody targeted at an enzyme considered to be important to collagen cross-linking did not produce any improvement in progression-free survival (PFS), according to results of a multicenter study presented at the annual congress of the European Respiratory Society.

“This was such a negative study, there is no point in doing another,” reported Ganesh Raghu, MD, director of the Pulmonary Fibrosis Program at the University of Washington Medical Center, Seattle.

The focus of this study was simtuzumab, a monoclonal antibody targeted at lysyl oxidase like 2 (LOXL2), an enzyme which catalyzes a step in the formation of collagen crosslinks, which are thought to be important in fibrosis formation. Simtuzumab has been entered into clinical trials for treatment of several forms of fibrosis, including fibrosis in the liver.

“In animal models, simtuzumab has demonstrated efficacy in reducing fibrosis when administered prior to fibrosis formation or after the process has already begun,” Dr. Raghu explained. He said a large trial was initiated in IPF because the agent seemed so promising and because a large study was thought to be the best strategy to arrive at a definitive answer regarding safety and efficacy.

The drug was found safe but not effective. The independent data monitoring and safety committee terminated the trial early for futility.

In the study, 544 IPF patients were randomized to 125 mg simtuzumab or placebo administered subcutaneously once weekly. The primary endpoint was PFS, but there were a large number of secondary endpoints including hospitalization for progressive disease, change in 6-minute walk distance (6MWD), and overall survival.

For the endpoint of PFS, “there was absolutely no difference” between the groups receiving simtuzumab or placebo. When the patients were stratified for demonstrating above or below median expression of LOXL2, which was a prespecified analysis for the trial, there was still no difference between groups. Even when those in the top quarter percentile of LOXL2 expression were compared with those with less [expression of the enzyme], there was still “absolutely no difference.”

There was also no significant evidence of benefit for simtuzumab observed on key secondary endpoints, such as overall survival. When patients were stratified by baseline lung function as expressed by percentage of predicted forced expiratory volume in 1 second (FEV₁), there was no signal of benefit for those with severe, moderate, or mild impairment.

One criticism of this study raised after the presentation was that patients with 26% or greater of predicted FEV₁ were permitted into the study. It was suggested that such patients would be expected to already have a high degree of fibrosis and therefore would be less likely to benefit from an antifibrosis therapy. Dr. Raghu acknowledged this criticism, but he said it was important to include patients with advanced disease in order to generate an adequate event rate. Even with inclusion of patients with severe lung impairment, the mortality rate was less than 10%.

He concluded that there was no signal of benefit even among those with the greatest expression of the target.

“We absolutely need better markers for IPF,” Dr. Raghu maintained. While other members of the LOXL family of enzymes may still prove to be valuable markers of IPF risk and targets of therapy, these data appear to rule out a therapeutic role for blocking LOXL2.

Dr. Raghu is a consultant for Boehringer Ingelheim, Biogen, FibroGen, Gilead, Janssen, MedImmune, Promedior, Sanofi-Aventis, and Veracyte.

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

rhnews@frontlinemedcom.com

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

rhnews@frontlinemedcom.com

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

rhnews@frontlinemedcom.com

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

jevans@frontlinemedcom.com

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

jevans@frontlinemedcom.com

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

jevans@frontlinemedcom.com

ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.

“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.

Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.

The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.

Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.

Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.

Joint damage

In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.

Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.

Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.

Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.

“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.

Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.

“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.

She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.

Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.

ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.

“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.

Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.

The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.

Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.

Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.

Joint damage

In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.

Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.

Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.

Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.

“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.

Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.

“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.

She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.

Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.

ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.

“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.

Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.

The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.

Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.

Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.

Joint damage

In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.

Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.

Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.

Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.

“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.

Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.

“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.

She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.

Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.

The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.

The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.

IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.

“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.

More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.

klennon@frontlinemedcom.com

The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.

The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.

IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.

“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.

More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.

klennon@frontlinemedcom.com

The number of patients enrolled in the Idiopathic Pulmonary Fibrosis–Prospective Outcomes (IPF-PRO) Registry will be increased to 1,500, Boehringer Ingelheim Pharmaceuticals and the Duke Clinical Research Institute have announced.

The organizations plan to accomplish this goal by increasing the number of sites they use to gather IPF patient data, according to a statement; the patients enrolled in the registry will now come from 45 sites instead of 18 sites.

IPF-PRO, which was launched in June 2014, is the first multicenter longitudinal disease state registry in the United States focused specifically on IPF. It was designed for the purpose of studying the progression of IPF and the effectiveness of various treatment approaches for the disease. The registry includes a biorepository that stores blood samples that provide patient genetic material.

“In collecting data from a larger, more diverse group of patients ... this registry will allow us to better assess the impact of the disease over time on clinical and patient-centered outcomes,” said Scott M. Palmer, MD, director of pulmonary research at the Duke Clinical Research Institute, Durham, N.C., in the statement.

More information on the registry is available at clinicaltrials.gov/ct2/show/NCT01915511.

klennon@frontlinemedcom.com

Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.

For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.

©kgtoh/Thinkstock

In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.

“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.

They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”

Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).

jevans@frontlinemedcom.com

Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.

For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.

©kgtoh/Thinkstock

In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.

“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.

They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”

Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).

jevans@frontlinemedcom.com

Patients with rheumatoid arthritis have steadily made their initial clinical presentation with shorter and shorter symptom durations and less severe inflammation from the early 1990s into the 2010s, but this paradoxically has coincided with gradual increases in the severity of patient-reported outcome measures, according to findings from the Leiden Early Arthritis Cohort.

For 1,406 patients who met 2010 European League Against Rheumatism/American College of Rheumatology rheumatoid arthritis (RA) criteria during 1993-2015, investigators led by Wouter P. Nieuwenhuis, MD, of the department of rheumatology at Leiden (the Netherlands) University Medical Center found that the symptom duration at initial presentation declined significantly from a median 138 days during 1993-1996 to 97 days during 2011-2015. Although the frequency of autoantibodies at presentation did not change significantly, the median number of swollen joints decreased from 12 to 6, median tender joints declined from 21 to 10, and median C-reactive protein levels dropped from 24 mg/L to 10 mg/L (all P values less than .001). All these measures declined steadily during the five time periods analyzed (1993-1996, 1997-2000, 2001-2005, 2006-2010, 2011-2015). Median scores on the Health Assessment Questionnaire, which measures functional disability, stayed the same in all five time periods.

©kgtoh/Thinkstock

In contrast, patient-reported outcomes measures (PROMs) on visual analog scales for pain, fatigue, and disease activity all rose significantly from 1993-1996 to 2011-2015.

“Presumably, the present findings are not specific for RA, but reflect a general increase in societal pressure posed upon the individual over the years (i.e., society has become more demanding), whereby smaller health problems, which might be less visible, could be experienced as more disabling. In parallel, patients may also have higher health expectations themselves. Both phenomena likely contribute to a shift of reference when reporting outcomes,” the researchers wrote.

They added that the current findings, in light of previous studies that found that PROMs are not responsive to changes in the severity of inflammation, “raise the question if it is known what PROMs actually measure. Furthermore, this may have consequences for the monitoring of RA using PROMs or composite scores (e.g., Disease Activity Score or Simple Disease Activity Index) for defining remission.”

Read the full study in Annals of the Rheumatic Diseases (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209949).

jevans@frontlinemedcom.com

DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

MIAMI – Reaching a consensus on measurement and assessment of flare in psoriatic arthritis remains challenging, especially with no widely accepted definition and differing opinions among patients and physicians. But getting standard evaluation of flare under control is critical for both clinical and research outcomes.

Through a series of patient interviews, physician surveys, and lessons learned in rheumatoid arthritis, the GRAPPA Flare Project is close to a validated flare instrument. A 10-question flare assessment tool is now in the final validation stage, according to a presentation at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Flare is a clearly personal experience and varies from patient to patient. It’s clear that physicians and patients have clearly different ideas of what flare is. Bringing those two worlds together was a challenge,” Philip Helliwell, MD, of Leeds (England) University and GRAPPA president, said at the meeting.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

“Some societies – I’m not going to mention any names – have gone down the route of a definition of flare linked to disease activity measures. We have not done this,” Dr. Helliwell said.

Instead, the Flare Project is taking a patient-driven and physician-reviewed approach. Investigators cast a wide net, identifying 79 factors important to patients in six major domains: skin, joint, emotional, participation, fatigue, and unclassified. The results were published in 2015 (Rheumatology [Oxford]. 2015 Aug;54[8]:1448-53). Through a Delphi survey, physicians reviewed these considerations. Then GRAPPA identified items important to both patients and physicians and developed a preliminary flare instrument.

Unlike most assessment tools for psoriatic disease, the new instrument includes patient-reported emotional well-being. Niti Goel, MD, of Duke University, Durham, N.C., said that physicians do not always ask patients about the psychological impact of their disease, so the tool “could provide additional information.”

Another goal of the project is to provide standard answers to some of the common questions related to psoriatic arthritis, including: What exactly is a flare? Does the definition truly capture the worsening of disease? Are there different types of flares? Is flare different if you start from a point of high disease activity? What self-management and other interventions are effective for flare?

GRAPPA adopted a definition of flare developed from rheumatoid arthritis, stating that flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy (J Rheumatol. 2009 Oct;36[10]:2335-41).

“It took [them] some time to get to that definition,” Dr. Helliwell said. “We know from rheumatoid arthritis that there is a lot more to a flare than joint swelling and pain.”

The GRAPPA flare tool is now in the validation stage, Dr. Helliwell said, and will be tested in several studies, including a prospective multicenter study where the 10-item questionnaire will be administered to patients.

A meeting attendee commented that the patient and physician global scales are sufficient and asked: “Is there really a need for a flare instrument?”

“I accept what you are saying, but I would also retort that knowledge is power, and the more information we get, the more we know about what we are doing,” Dr. Helliwell said. “We are going to collect all our information – physician global, patient global, composite disease measures – everything within that study.”

Dr. Helliwell and Dr. Goel reported having no relevant financial disclosures.

MIAMI – Reaching a consensus on measurement and assessment of flare in psoriatic arthritis remains challenging, especially with no widely accepted definition and differing opinions among patients and physicians. But getting standard evaluation of flare under control is critical for both clinical and research outcomes.

Through a series of patient interviews, physician surveys, and lessons learned in rheumatoid arthritis, the GRAPPA Flare Project is close to a validated flare instrument. A 10-question flare assessment tool is now in the final validation stage, according to a presentation at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Flare is a clearly personal experience and varies from patient to patient. It’s clear that physicians and patients have clearly different ideas of what flare is. Bringing those two worlds together was a challenge,” Philip Helliwell, MD, of Leeds (England) University and GRAPPA president, said at the meeting.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

“Some societies – I’m not going to mention any names – have gone down the route of a definition of flare linked to disease activity measures. We have not done this,” Dr. Helliwell said.

Instead, the Flare Project is taking a patient-driven and physician-reviewed approach. Investigators cast a wide net, identifying 79 factors important to patients in six major domains: skin, joint, emotional, participation, fatigue, and unclassified. The results were published in 2015 (Rheumatology [Oxford]. 2015 Aug;54[8]:1448-53). Through a Delphi survey, physicians reviewed these considerations. Then GRAPPA identified items important to both patients and physicians and developed a preliminary flare instrument.

Unlike most assessment tools for psoriatic disease, the new instrument includes patient-reported emotional well-being. Niti Goel, MD, of Duke University, Durham, N.C., said that physicians do not always ask patients about the psychological impact of their disease, so the tool “could provide additional information.”

Another goal of the project is to provide standard answers to some of the common questions related to psoriatic arthritis, including: What exactly is a flare? Does the definition truly capture the worsening of disease? Are there different types of flares? Is flare different if you start from a point of high disease activity? What self-management and other interventions are effective for flare?

GRAPPA adopted a definition of flare developed from rheumatoid arthritis, stating that flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy (J Rheumatol. 2009 Oct;36[10]:2335-41).

“It took [them] some time to get to that definition,” Dr. Helliwell said. “We know from rheumatoid arthritis that there is a lot more to a flare than joint swelling and pain.”

The GRAPPA flare tool is now in the validation stage, Dr. Helliwell said, and will be tested in several studies, including a prospective multicenter study where the 10-item questionnaire will be administered to patients.

A meeting attendee commented that the patient and physician global scales are sufficient and asked: “Is there really a need for a flare instrument?”

“I accept what you are saying, but I would also retort that knowledge is power, and the more information we get, the more we know about what we are doing,” Dr. Helliwell said. “We are going to collect all our information – physician global, patient global, composite disease measures – everything within that study.”

Dr. Helliwell and Dr. Goel reported having no relevant financial disclosures.

MIAMI – Reaching a consensus on measurement and assessment of flare in psoriatic arthritis remains challenging, especially with no widely accepted definition and differing opinions among patients and physicians. But getting standard evaluation of flare under control is critical for both clinical and research outcomes.

Through a series of patient interviews, physician surveys, and lessons learned in rheumatoid arthritis, the GRAPPA Flare Project is close to a validated flare instrument. A 10-question flare assessment tool is now in the final validation stage, according to a presentation at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Flare is a clearly personal experience and varies from patient to patient. It’s clear that physicians and patients have clearly different ideas of what flare is. Bringing those two worlds together was a challenge,” Philip Helliwell, MD, of Leeds (England) University and GRAPPA president, said at the meeting.

James Heilman, MD/Wikimedia Commons/CC BY-SA 3.0

“Some societies – I’m not going to mention any names – have gone down the route of a definition of flare linked to disease activity measures. We have not done this,” Dr. Helliwell said.

Instead, the Flare Project is taking a patient-driven and physician-reviewed approach. Investigators cast a wide net, identifying 79 factors important to patients in six major domains: skin, joint, emotional, participation, fatigue, and unclassified. The results were published in 2015 (Rheumatology [Oxford]. 2015 Aug;54[8]:1448-53). Through a Delphi survey, physicians reviewed these considerations. Then GRAPPA identified items important to both patients and physicians and developed a preliminary flare instrument.

Unlike most assessment tools for psoriatic disease, the new instrument includes patient-reported emotional well-being. Niti Goel, MD, of Duke University, Durham, N.C., said that physicians do not always ask patients about the psychological impact of their disease, so the tool “could provide additional information.”

Another goal of the project is to provide standard answers to some of the common questions related to psoriatic arthritis, including: What exactly is a flare? Does the definition truly capture the worsening of disease? Are there different types of flares? Is flare different if you start from a point of high disease activity? What self-management and other interventions are effective for flare?

GRAPPA adopted a definition of flare developed from rheumatoid arthritis, stating that flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy (J Rheumatol. 2009 Oct;36[10]:2335-41).

“It took [them] some time to get to that definition,” Dr. Helliwell said. “We know from rheumatoid arthritis that there is a lot more to a flare than joint swelling and pain.”

The GRAPPA flare tool is now in the validation stage, Dr. Helliwell said, and will be tested in several studies, including a prospective multicenter study where the 10-item questionnaire will be administered to patients.

A meeting attendee commented that the patient and physician global scales are sufficient and asked: “Is there really a need for a flare instrument?”

“I accept what you are saying, but I would also retort that knowledge is power, and the more information we get, the more we know about what we are doing,” Dr. Helliwell said. “We are going to collect all our information – physician global, patient global, composite disease measures – everything within that study.”

Dr. Helliwell and Dr. Goel reported having no relevant financial disclosures.

An autoinjector for subcutaneously administering abatacept (Orencia) has been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis, making it the third delivery method available for patients to use the biologic.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

Abatacept is also available for intravenous infusion and subcutaneous administration with a prefilled syringe. With a single button push, the new Orencia ClickJect autoinjector delivers 125 mg of the drug over the course of 15 seconds and also confirms the injection. The autoinjector’s design is meant to allow patients with rheumatoid arthritis to firmly hold, operate, and control the device, according to an announcement from the manufacturer, Bristol-Myers Squibb.

Although abatacept is approved to treat polyarticular juvenile idiopathic arthritis in patients aged 6 years and older, subcutaneous formulations of the drug have not been studied in patients younger than 18 years.

jevans@frontlinemedcom.com

An autoinjector for subcutaneously administering abatacept (Orencia) has been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis, making it the third delivery method available for patients to use the biologic.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

Abatacept is also available for intravenous infusion and subcutaneous administration with a prefilled syringe. With a single button push, the new Orencia ClickJect autoinjector delivers 125 mg of the drug over the course of 15 seconds and also confirms the injection. The autoinjector’s design is meant to allow patients with rheumatoid arthritis to firmly hold, operate, and control the device, according to an announcement from the manufacturer, Bristol-Myers Squibb.

Although abatacept is approved to treat polyarticular juvenile idiopathic arthritis in patients aged 6 years and older, subcutaneous formulations of the drug have not been studied in patients younger than 18 years.

jevans@frontlinemedcom.com

An autoinjector for subcutaneously administering abatacept (Orencia) has been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis, making it the third delivery method available for patients to use the biologic.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

Abatacept is also available for intravenous infusion and subcutaneous administration with a prefilled syringe. With a single button push, the new Orencia ClickJect autoinjector delivers 125 mg of the drug over the course of 15 seconds and also confirms the injection. The autoinjector’s design is meant to allow patients with rheumatoid arthritis to firmly hold, operate, and control the device, according to an announcement from the manufacturer, Bristol-Myers Squibb.

Although abatacept is approved to treat polyarticular juvenile idiopathic arthritis in patients aged 6 years and older, subcutaneous formulations of the drug have not been studied in patients younger than 18 years.

jevans@frontlinemedcom.com

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

emechcatie@frontlinemedcom.com

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

emechcatie@frontlinemedcom.com

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.

Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”

The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.

Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.

emechcatie@frontlinemedcom.com