Jeff Evans

Proper administration of intravenous biologics should take place under the close supervision of a physician in a physician’s office, infusion center, or hospital rather than in a patient’s home in order to address potential infusion reactions that can range from mild to life threatening, according to a position statement issued by the American College of Rheumatology’s Committee on Rheumatologic Care.

The “Patient Safety and Site of Service for Infusible Biologics” statement, issued in late February, comes in opposition to “policies that require home infusion” that appear to seek potential cost savings with home infusions rather than meet the standard of care with on-site physician supervision.

Trish233/Thinkstock

“One observation made by some but not all payers is that infusible biologics are about twice as expensive when infused in a hospital-based infusion center as compared to other locations, such as a clinic-based infusion center or the patient’s home. Thus, some payers are rolling out policies designed to shift patients from hospital-based infusion centers to less expensive sites. The ACR is opposed to policies that would force patients, solely for the purpose of cost containment, to receive infusible biologics in an improperly supervised setting. The purpose of the position statement is to outline that stance,” Dr. Douglas W. White, chair of the ACR’s Committee on Rheumatologic Care, said in an interview.

He noted that he’s “been in on conversations with two payers who are implementing policies to move patients away from hospital-based infusions, but we are aware that others are in various stages of implementing such policies, too. It’s not so much an issue of critical mass for us, rather we’re just trying to keep ahead of the trends, and we think this will be a big trend.”

The potential for adverse reactions is not uncommon during intravenous administration of biologics, the committee wrote, noting, for example, that 10% of patients given infliximab have acute infusion reactions. On-site physicians such as rheumatologists who have experience with the “tremendous heterogeneity of patients with autoimmune disease and the diversity of conditions treated with biologics” can determine the severity of infusion reactions and decide whether or not it is safe to continue a particular biologic agent, in addition to providing reassurance to patients during acute and potentially severe reactions, according to the ACR statement.

Infusion reactions can range in severity from a mild rash to life-threatening anaphylaxis that can involve multiple organ systems leading to respiratory and cardiovascular collapse and requiring immediate treatment with medications such as epinephrine or intravenous glucocorticoids.

The position statement recognizes unusual situations in which home infusion is necessary for a patient to receive treatment because of transportation problems to a medical facility or comorbid conditions in which the risk of no treatment may outweigh the risk of home infusion. In these circumstances, the ACR “encourages providers in such unusual and difficult situations to make the best medical decision based on the individual needs of the patient. Routine home infusion of biologics is considered an unnecessary and dangerous risk to patients and violates our current clinical standards of practice.”

Requirements for using home infusion also threaten “to reduce access to” intravenous biologics, the ACR contends, because “specially trained physicians are less likely to prescribe treatments that are not properly administered in the safest clinical setting [and] patient fear of biologic therapy may lead to noncompliance and inadequate control of disease.”

The ACR noted that home administration of subcutaneous biologics is medically appropriate and the injection site reactions that can occur with their use are often easily managed.

[email protected]

Proper administration of intravenous biologics should take place under the close supervision of a physician in a physician’s office, infusion center, or hospital rather than in a patient’s home in order to address potential infusion reactions that can range from mild to life threatening, according to a position statement issued by the American College of Rheumatology’s Committee on Rheumatologic Care.

The “Patient Safety and Site of Service for Infusible Biologics” statement, issued in late February, comes in opposition to “policies that require home infusion” that appear to seek potential cost savings with home infusions rather than meet the standard of care with on-site physician supervision.

Trish233/Thinkstock

“One observation made by some but not all payers is that infusible biologics are about twice as expensive when infused in a hospital-based infusion center as compared to other locations, such as a clinic-based infusion center or the patient’s home. Thus, some payers are rolling out policies designed to shift patients from hospital-based infusion centers to less expensive sites. The ACR is opposed to policies that would force patients, solely for the purpose of cost containment, to receive infusible biologics in an improperly supervised setting. The purpose of the position statement is to outline that stance,” Dr. Douglas W. White, chair of the ACR’s Committee on Rheumatologic Care, said in an interview.

He noted that he’s “been in on conversations with two payers who are implementing policies to move patients away from hospital-based infusions, but we are aware that others are in various stages of implementing such policies, too. It’s not so much an issue of critical mass for us, rather we’re just trying to keep ahead of the trends, and we think this will be a big trend.”

The potential for adverse reactions is not uncommon during intravenous administration of biologics, the committee wrote, noting, for example, that 10% of patients given infliximab have acute infusion reactions. On-site physicians such as rheumatologists who have experience with the “tremendous heterogeneity of patients with autoimmune disease and the diversity of conditions treated with biologics” can determine the severity of infusion reactions and decide whether or not it is safe to continue a particular biologic agent, in addition to providing reassurance to patients during acute and potentially severe reactions, according to the ACR statement.

Infusion reactions can range in severity from a mild rash to life-threatening anaphylaxis that can involve multiple organ systems leading to respiratory and cardiovascular collapse and requiring immediate treatment with medications such as epinephrine or intravenous glucocorticoids.

The position statement recognizes unusual situations in which home infusion is necessary for a patient to receive treatment because of transportation problems to a medical facility or comorbid conditions in which the risk of no treatment may outweigh the risk of home infusion. In these circumstances, the ACR “encourages providers in such unusual and difficult situations to make the best medical decision based on the individual needs of the patient. Routine home infusion of biologics is considered an unnecessary and dangerous risk to patients and violates our current clinical standards of practice.”

Requirements for using home infusion also threaten “to reduce access to” intravenous biologics, the ACR contends, because “specially trained physicians are less likely to prescribe treatments that are not properly administered in the safest clinical setting [and] patient fear of biologic therapy may lead to noncompliance and inadequate control of disease.”

The ACR noted that home administration of subcutaneous biologics is medically appropriate and the injection site reactions that can occur with their use are often easily managed.

[email protected]

Proper administration of intravenous biologics should take place under the close supervision of a physician in a physician’s office, infusion center, or hospital rather than in a patient’s home in order to address potential infusion reactions that can range from mild to life threatening, according to a position statement issued by the American College of Rheumatology’s Committee on Rheumatologic Care.

The “Patient Safety and Site of Service for Infusible Biologics” statement, issued in late February, comes in opposition to “policies that require home infusion” that appear to seek potential cost savings with home infusions rather than meet the standard of care with on-site physician supervision.

Trish233/Thinkstock

“One observation made by some but not all payers is that infusible biologics are about twice as expensive when infused in a hospital-based infusion center as compared to other locations, such as a clinic-based infusion center or the patient’s home. Thus, some payers are rolling out policies designed to shift patients from hospital-based infusion centers to less expensive sites. The ACR is opposed to policies that would force patients, solely for the purpose of cost containment, to receive infusible biologics in an improperly supervised setting. The purpose of the position statement is to outline that stance,” Dr. Douglas W. White, chair of the ACR’s Committee on Rheumatologic Care, said in an interview.

He noted that he’s “been in on conversations with two payers who are implementing policies to move patients away from hospital-based infusions, but we are aware that others are in various stages of implementing such policies, too. It’s not so much an issue of critical mass for us, rather we’re just trying to keep ahead of the trends, and we think this will be a big trend.”

The potential for adverse reactions is not uncommon during intravenous administration of biologics, the committee wrote, noting, for example, that 10% of patients given infliximab have acute infusion reactions. On-site physicians such as rheumatologists who have experience with the “tremendous heterogeneity of patients with autoimmune disease and the diversity of conditions treated with biologics” can determine the severity of infusion reactions and decide whether or not it is safe to continue a particular biologic agent, in addition to providing reassurance to patients during acute and potentially severe reactions, according to the ACR statement.

Infusion reactions can range in severity from a mild rash to life-threatening anaphylaxis that can involve multiple organ systems leading to respiratory and cardiovascular collapse and requiring immediate treatment with medications such as epinephrine or intravenous glucocorticoids.

The position statement recognizes unusual situations in which home infusion is necessary for a patient to receive treatment because of transportation problems to a medical facility or comorbid conditions in which the risk of no treatment may outweigh the risk of home infusion. In these circumstances, the ACR “encourages providers in such unusual and difficult situations to make the best medical decision based on the individual needs of the patient. Routine home infusion of biologics is considered an unnecessary and dangerous risk to patients and violates our current clinical standards of practice.”

Requirements for using home infusion also threaten “to reduce access to” intravenous biologics, the ACR contends, because “specially trained physicians are less likely to prescribe treatments that are not properly administered in the safest clinical setting [and] patient fear of biologic therapy may lead to noncompliance and inadequate control of disease.”

The ACR noted that home administration of subcutaneous biologics is medically appropriate and the injection site reactions that can occur with their use are often easily managed.

[email protected]

Antisclerostin monoclonal antibodies have shown their ability to increase bone density in phase II and III trials of men and women with osteoporosis but could potentially have the opposite effect in patients with rheumatoid arthritis or other chronic inflammatory diseases in which tumor necrosis factor–alpha (TNF-alpha) plays an important role, according to new research.

The new work, conducted by Corinna Wehmeyer, Ph.D., of the Institute of Experimental Musculoskeletal Medicine at University Hospital Muenster (Germany) and her colleagues, shows that the bone formation–inhibiting protein sclerostin is not expressed in bone only, as was previously thought, but is also expressed on the synovial cells of patients with rheumatoid arthritis (RA).

F. Rauch et al., Science Translational Medicine (2016)

Dr. Wehmeyer and her associates were surprised to find that inhibiting sclerostin in a human TNF-alpha transgenic mouse model of RA actually accelerated joint damage rather than prevented it, suggesting that sclerostin actually had a protective role in the presence of chronic TNF-alpha–mediated inflammation. They confirmed this by demonstrating that sclerostin inhibited TNF-alpha signaling in fibroblast-like synoviocytes and showing that blocking sclerostin caused less or little worsening of bone erosions in mouse models of RA that are more dependent on a robust T and B cell response accompanied by high cytokine expression within the joint, rather than damage driven by TNF-alpha.

“These findings strongly suggest that in chronic TNF-alpha–mediated inflammation, sclerostin expression is upregulated as part of an attempt to reestablish bone homeostasis, where it exerts protective functions,” the authors wrote (Sci Transl Med. 2016 Mar 16;8:330ra34. doi: 10.1126/scitranslmed.aac4351).

The research needs confirmation in humans with RA and potentially in other chronic inflammatory diseases in which TNF-alpha plays an important role. “Nevertheless, the preliminary data in three different models indicate that sclerostin antibody therapy could be contraindicated in patients with chronic TNF-alpha–dependent inflammatory conditions. The possibility of adverse pathological effects means that caution should be taken both when considering such treatment in RA or in patients with chronic TNF-alpha–dependent comorbidities. Thus, to translate these findings to patients, first strategies to use sclerostin inhibition should exclude inflammatory comorbidities and very thoroughly monitor inflammatory events in patients to which such therapies are applied,” the researchers advised.

In an editorial, Dr. Frank Rauch of McGill University, Montreal, and Dr. Rick Adachi of the department of rheumatology at McMaster University, Hamilton, Ont., wrote that antisclerostin “treatment might accelerate joint destruction, at least when the inflammatory process is not quelled first. Patients with established RA usually undergo anti-inflammatory treatment, and it is unclear whether sclerostin inactivation would be detrimental in this context. Mouse data suggest that antisclerostin treatment might bring about regression of bone erosions when combined with TNF-alpha inhibition. The new work mirrors the situation of patients who have unrecognized RA while on antisclerostin therapy or who develop RA while receiving this treatment” (Sci Transl Med. 2016 Mar 16;8:330fs7. doi: 10.1126/scitranslmed.aaf4628).

Antisclerostin antibodies in trials

Trials of the antisclerostin monoclonal antibodies romosozumab and blosozumab have been successful in treating postmenopausal women and men with osteoporosis.

Romosozumab codevelopers UCB and Amgen reported that the biologic agent significantly reduced the rate of new vertebral fractures by 73% versus placebo at 12 months in the randomized, double-blind phase III FRAME (Fracture Study in Postmenopausal Women With Osteoporosis) study. In the 7,180-patient trial, the reduction was 75% versus placebo at 24 months after both treatment groups had been transitioned to denosumab given every 6 months in the second year of treatment. Romosozumab also significantly lowered the relative risk of clinical fractures (composite of vertebral and nonvertebral fractures) by 36% at 12 months, but the difference was not statistically significant at 24 months.

In the initial 12-month treatment period, the most commonly reported adverse events in both arms (greater than 10%) were arthralgia, nasopharyngitis, and back pain. There were no differences in the proportions of patients who reported hearing loss or worsening of knee osteoarthritis. There were two positively adjudicated events of osteonecrosis of the jaw in the romosozumab treatment group, one after completing romosozumab dosing and the other after completing romosozumab treatment and receiving the initial dose of denosumab. There was one positively adjudicated event of atypical femoral fracture after 3 months of romosozumab treatment.

Phase III results from the 244-patient BRIDGE (Placebo-Controlled Study Evaluating the Efficacy and Safety of Romosozumab in Treating Men With Osteoporosis) trial found a significant increase in bone mineral density (BMD) at the lumbar spine at 12 months, which was the study’s primary endpoint. Other significant increases in femoral neck and total hip BMD were detected at 12 months. Cardiovascular severe adverse events occurred in 4.9% of men on romosozumab and 2.5% on placebo, including death in 0.6% and 1.2%, respectively. At least 5% or more of patients who received romosozumab reported nasopharyngitis, back pain, hypertension, headache, and constipation. About 5% of patients who received romosozumab in each trial had injection-site reactions, most of which were mild.

A phase II trial of blosozumab in 120 postmenopausal women with low bone mineral density (mean lumbar spine T-score –2.8) showed that the drug increased BMD in the lumbar spine by 17.7% above baseline at 52 weeks, femoral neck by 8.4%, and total hip by 6.2%, compared with decreases of 1.6%, 0.6%, and 0.7%, respectively, with placebo (J Bone Miner Res. 2015 Feb;30[2]:216-24). However, mild injection-site reactions were reported by up to 40% of women taking blosozumab, and 35% developed antidrug antibodies after exposure to blosozumab. Eli Lilly, its developer, is looking at possible ways to reformulate the drug before it moves to phase III.

The study in Science Translational Medicine was supported by the German Research Foundation. The authors had no competing interests to disclose.

[email protected]

Antisclerostin monoclonal antibodies have shown their ability to increase bone density in phase II and III trials of men and women with osteoporosis but could potentially have the opposite effect in patients with rheumatoid arthritis or other chronic inflammatory diseases in which tumor necrosis factor–alpha (TNF-alpha) plays an important role, according to new research.

The new work, conducted by Corinna Wehmeyer, Ph.D., of the Institute of Experimental Musculoskeletal Medicine at University Hospital Muenster (Germany) and her colleagues, shows that the bone formation–inhibiting protein sclerostin is not expressed in bone only, as was previously thought, but is also expressed on the synovial cells of patients with rheumatoid arthritis (RA).

F. Rauch et al., Science Translational Medicine (2016)

Dr. Wehmeyer and her associates were surprised to find that inhibiting sclerostin in a human TNF-alpha transgenic mouse model of RA actually accelerated joint damage rather than prevented it, suggesting that sclerostin actually had a protective role in the presence of chronic TNF-alpha–mediated inflammation. They confirmed this by demonstrating that sclerostin inhibited TNF-alpha signaling in fibroblast-like synoviocytes and showing that blocking sclerostin caused less or little worsening of bone erosions in mouse models of RA that are more dependent on a robust T and B cell response accompanied by high cytokine expression within the joint, rather than damage driven by TNF-alpha.

“These findings strongly suggest that in chronic TNF-alpha–mediated inflammation, sclerostin expression is upregulated as part of an attempt to reestablish bone homeostasis, where it exerts protective functions,” the authors wrote (Sci Transl Med. 2016 Mar 16;8:330ra34. doi: 10.1126/scitranslmed.aac4351).

The research needs confirmation in humans with RA and potentially in other chronic inflammatory diseases in which TNF-alpha plays an important role. “Nevertheless, the preliminary data in three different models indicate that sclerostin antibody therapy could be contraindicated in patients with chronic TNF-alpha–dependent inflammatory conditions. The possibility of adverse pathological effects means that caution should be taken both when considering such treatment in RA or in patients with chronic TNF-alpha–dependent comorbidities. Thus, to translate these findings to patients, first strategies to use sclerostin inhibition should exclude inflammatory comorbidities and very thoroughly monitor inflammatory events in patients to which such therapies are applied,” the researchers advised.

In an editorial, Dr. Frank Rauch of McGill University, Montreal, and Dr. Rick Adachi of the department of rheumatology at McMaster University, Hamilton, Ont., wrote that antisclerostin “treatment might accelerate joint destruction, at least when the inflammatory process is not quelled first. Patients with established RA usually undergo anti-inflammatory treatment, and it is unclear whether sclerostin inactivation would be detrimental in this context. Mouse data suggest that antisclerostin treatment might bring about regression of bone erosions when combined with TNF-alpha inhibition. The new work mirrors the situation of patients who have unrecognized RA while on antisclerostin therapy or who develop RA while receiving this treatment” (Sci Transl Med. 2016 Mar 16;8:330fs7. doi: 10.1126/scitranslmed.aaf4628).

Antisclerostin antibodies in trials

Trials of the antisclerostin monoclonal antibodies romosozumab and blosozumab have been successful in treating postmenopausal women and men with osteoporosis.

Romosozumab codevelopers UCB and Amgen reported that the biologic agent significantly reduced the rate of new vertebral fractures by 73% versus placebo at 12 months in the randomized, double-blind phase III FRAME (Fracture Study in Postmenopausal Women With Osteoporosis) study. In the 7,180-patient trial, the reduction was 75% versus placebo at 24 months after both treatment groups had been transitioned to denosumab given every 6 months in the second year of treatment. Romosozumab also significantly lowered the relative risk of clinical fractures (composite of vertebral and nonvertebral fractures) by 36% at 12 months, but the difference was not statistically significant at 24 months.

In the initial 12-month treatment period, the most commonly reported adverse events in both arms (greater than 10%) were arthralgia, nasopharyngitis, and back pain. There were no differences in the proportions of patients who reported hearing loss or worsening of knee osteoarthritis. There were two positively adjudicated events of osteonecrosis of the jaw in the romosozumab treatment group, one after completing romosozumab dosing and the other after completing romosozumab treatment and receiving the initial dose of denosumab. There was one positively adjudicated event of atypical femoral fracture after 3 months of romosozumab treatment.

Phase III results from the 244-patient BRIDGE (Placebo-Controlled Study Evaluating the Efficacy and Safety of Romosozumab in Treating Men With Osteoporosis) trial found a significant increase in bone mineral density (BMD) at the lumbar spine at 12 months, which was the study’s primary endpoint. Other significant increases in femoral neck and total hip BMD were detected at 12 months. Cardiovascular severe adverse events occurred in 4.9% of men on romosozumab and 2.5% on placebo, including death in 0.6% and 1.2%, respectively. At least 5% or more of patients who received romosozumab reported nasopharyngitis, back pain, hypertension, headache, and constipation. About 5% of patients who received romosozumab in each trial had injection-site reactions, most of which were mild.

A phase II trial of blosozumab in 120 postmenopausal women with low bone mineral density (mean lumbar spine T-score –2.8) showed that the drug increased BMD in the lumbar spine by 17.7% above baseline at 52 weeks, femoral neck by 8.4%, and total hip by 6.2%, compared with decreases of 1.6%, 0.6%, and 0.7%, respectively, with placebo (J Bone Miner Res. 2015 Feb;30[2]:216-24). However, mild injection-site reactions were reported by up to 40% of women taking blosozumab, and 35% developed antidrug antibodies after exposure to blosozumab. Eli Lilly, its developer, is looking at possible ways to reformulate the drug before it moves to phase III.

The study in Science Translational Medicine was supported by the German Research Foundation. The authors had no competing interests to disclose.

[email protected]

Antisclerostin monoclonal antibodies have shown their ability to increase bone density in phase II and III trials of men and women with osteoporosis but could potentially have the opposite effect in patients with rheumatoid arthritis or other chronic inflammatory diseases in which tumor necrosis factor–alpha (TNF-alpha) plays an important role, according to new research.

The new work, conducted by Corinna Wehmeyer, Ph.D., of the Institute of Experimental Musculoskeletal Medicine at University Hospital Muenster (Germany) and her colleagues, shows that the bone formation–inhibiting protein sclerostin is not expressed in bone only, as was previously thought, but is also expressed on the synovial cells of patients with rheumatoid arthritis (RA).

F. Rauch et al., Science Translational Medicine (2016)

Dr. Wehmeyer and her associates were surprised to find that inhibiting sclerostin in a human TNF-alpha transgenic mouse model of RA actually accelerated joint damage rather than prevented it, suggesting that sclerostin actually had a protective role in the presence of chronic TNF-alpha–mediated inflammation. They confirmed this by demonstrating that sclerostin inhibited TNF-alpha signaling in fibroblast-like synoviocytes and showing that blocking sclerostin caused less or little worsening of bone erosions in mouse models of RA that are more dependent on a robust T and B cell response accompanied by high cytokine expression within the joint, rather than damage driven by TNF-alpha.

“These findings strongly suggest that in chronic TNF-alpha–mediated inflammation, sclerostin expression is upregulated as part of an attempt to reestablish bone homeostasis, where it exerts protective functions,” the authors wrote (Sci Transl Med. 2016 Mar 16;8:330ra34. doi: 10.1126/scitranslmed.aac4351).

The research needs confirmation in humans with RA and potentially in other chronic inflammatory diseases in which TNF-alpha plays an important role. “Nevertheless, the preliminary data in three different models indicate that sclerostin antibody therapy could be contraindicated in patients with chronic TNF-alpha–dependent inflammatory conditions. The possibility of adverse pathological effects means that caution should be taken both when considering such treatment in RA or in patients with chronic TNF-alpha–dependent comorbidities. Thus, to translate these findings to patients, first strategies to use sclerostin inhibition should exclude inflammatory comorbidities and very thoroughly monitor inflammatory events in patients to which such therapies are applied,” the researchers advised.

In an editorial, Dr. Frank Rauch of McGill University, Montreal, and Dr. Rick Adachi of the department of rheumatology at McMaster University, Hamilton, Ont., wrote that antisclerostin “treatment might accelerate joint destruction, at least when the inflammatory process is not quelled first. Patients with established RA usually undergo anti-inflammatory treatment, and it is unclear whether sclerostin inactivation would be detrimental in this context. Mouse data suggest that antisclerostin treatment might bring about regression of bone erosions when combined with TNF-alpha inhibition. The new work mirrors the situation of patients who have unrecognized RA while on antisclerostin therapy or who develop RA while receiving this treatment” (Sci Transl Med. 2016 Mar 16;8:330fs7. doi: 10.1126/scitranslmed.aaf4628).

Antisclerostin antibodies in trials

Trials of the antisclerostin monoclonal antibodies romosozumab and blosozumab have been successful in treating postmenopausal women and men with osteoporosis.

Romosozumab codevelopers UCB and Amgen reported that the biologic agent significantly reduced the rate of new vertebral fractures by 73% versus placebo at 12 months in the randomized, double-blind phase III FRAME (Fracture Study in Postmenopausal Women With Osteoporosis) study. In the 7,180-patient trial, the reduction was 75% versus placebo at 24 months after both treatment groups had been transitioned to denosumab given every 6 months in the second year of treatment. Romosozumab also significantly lowered the relative risk of clinical fractures (composite of vertebral and nonvertebral fractures) by 36% at 12 months, but the difference was not statistically significant at 24 months.

In the initial 12-month treatment period, the most commonly reported adverse events in both arms (greater than 10%) were arthralgia, nasopharyngitis, and back pain. There were no differences in the proportions of patients who reported hearing loss or worsening of knee osteoarthritis. There were two positively adjudicated events of osteonecrosis of the jaw in the romosozumab treatment group, one after completing romosozumab dosing and the other after completing romosozumab treatment and receiving the initial dose of denosumab. There was one positively adjudicated event of atypical femoral fracture after 3 months of romosozumab treatment.

Phase III results from the 244-patient BRIDGE (Placebo-Controlled Study Evaluating the Efficacy and Safety of Romosozumab in Treating Men With Osteoporosis) trial found a significant increase in bone mineral density (BMD) at the lumbar spine at 12 months, which was the study’s primary endpoint. Other significant increases in femoral neck and total hip BMD were detected at 12 months. Cardiovascular severe adverse events occurred in 4.9% of men on romosozumab and 2.5% on placebo, including death in 0.6% and 1.2%, respectively. At least 5% or more of patients who received romosozumab reported nasopharyngitis, back pain, hypertension, headache, and constipation. About 5% of patients who received romosozumab in each trial had injection-site reactions, most of which were mild.

A phase II trial of blosozumab in 120 postmenopausal women with low bone mineral density (mean lumbar spine T-score –2.8) showed that the drug increased BMD in the lumbar spine by 17.7% above baseline at 52 weeks, femoral neck by 8.4%, and total hip by 6.2%, compared with decreases of 1.6%, 0.6%, and 0.7%, respectively, with placebo (J Bone Miner Res. 2015 Feb;30[2]:216-24). However, mild injection-site reactions were reported by up to 40% of women taking blosozumab, and 35% developed antidrug antibodies after exposure to blosozumab. Eli Lilly, its developer, is looking at possible ways to reformulate the drug before it moves to phase III.

The study in Science Translational Medicine was supported by the German Research Foundation. The authors had no competing interests to disclose.

[email protected]

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

Therapeutic goals set the tone for the American College of Rheumatology National Research Agenda 2016-2020 by calling for the discovery and development of new therapies for rheumatic disease; finding predictors of response and nonresponse to, and adverse events from therapy; and improving the understanding of how therapies should be used.

Those are the top 3 out of 15 goals facilitated by the ACR’s Committee on Research, which finalized the agenda after seeking input from members of the ACR and Association of Rheumatology Health Professionals (ARHP) living in the United States, and going through several rounds of refining and prioritizing the importance of goals through the input of clinicians, researchers, patients, and stakeholders. The Committee on Research uses the agenda to “set the compass for the organization in terms of research initiatives and facilitate the ACR’s advocacy for the research goals identified.”

©Tashatuvango/Thinkstock

Dr. Alexis R. Ogdie-Beatty, who jointly led the development of the agenda for the Committee on Research along with Dr. S. Louis Bridges, said that while the goals for 2016-2020 had a great deal of overlap with those of 2011-2015, “some of the topics that came up were different. Some of the topics were more specific than in the previous agenda. We have some idea how important these issues were to rheumatologists, given that rheumatologists (and patients) rated the importance of the items. Defining new therapeutic targets and developing new therapies for rheumatic diseases was by far the most highly rated goal by rheumatologists. Next most highly rated was to advocate for increased support for rheumatology research and rheumatology investigators – this was included as a supplementary goal that supports the rest of the agenda. Other newer items were those around determining how the changing health care landscape affects rheumatology patients and clinicians. In addition, nonpharmacologic therapy, adult outcomes of pediatric disease, and optimizing patient engagement were topics that were felt to be important. I think these highlight the input of clinicians in identifying research objectives.”

The 2016-2020 agenda is the third set of goals developed by the committee since 2005, and the first to “crowdsource” the important questions to ACR and ARHP members rather than be assembled solely by the committee.

The agenda arose from a multistage process that began with a web-based survey to the ACR/ARHP membership that asked respondents to “list the five most important research questions that need to be addressed over the next 5 years in order to improve the care for patients with rheumatic disease.” A selected group of 100 individuals representing patients, clinicians (academic and community), research (all types with diverse areas/diseases of interest), allied health professionals, pediatric and adult rheumatology, men and women, all career stages, and all regions of the country, used a Delphi exercise to rate 30 statements generated from the survey on a scale from 1 (not important) to 10 (very important). They had the option to provide comments. At a Leadership Summit, stakeholders from various nonprofit foundations associated with rheumatic diseases, the National Institutes of Health, and the president of the Rheumatology Research Foundation gave comments on a draft agenda to the Committee on Research, after which the committee discussed the results and input and then solicited further 1-10 ratings and comments on preliminary agenda goals from the same group of 100 individuals as in the second phase, plus an additional 17 clinicians.

Up next in the rank-ordering after therapeutic goals were three goals about understanding:

• The etiology, pathogenesis, and genetic basis of rheumatic diseases.

• Early disease states to improve early diagnosis, develop biomarkers for early detection, and determine how earlier treatment changes outcomes.

• The immune system and autoimmunity by defining autoimmunity triggers and determining how epigenetics affect disease susceptibility and inflammation.

The 5-year plan proposed developing improved outcome measures that incorporate patient self-reports, imaging, and measures of clinical response and disease activity. The agenda also seeks to gain better understanding of how patients with rheumatic disease, rheumatologists, and rheumatology health professionals are being affected by the changing U.S. health care landscape.

The plan calls for determining the role of nonpharmacologic therapy in the management of rheumatic disease (promoting and improving adherence to physical activity, finding optimal exercise prescriptions, and determining the role of diet on disease activity), as well as evaluating the role of regenerative medicine.

The agenda spells out the need for better engagement of patients in their care as well as for understanding how comorbidities are influenced by rheumatic disease and how pain and fatigue arise in rheumatic disease.

In two separate goals, committee members listed the importance of determining adult outcomes of pediatric rheumatic diseases and the effect of aging on the development, progression, and management of rheumatic diseases.

The Committee on Research identified three supplemental goals that support the others:

• Advocating for increased support for rheumatology research and rheumatology investigators.

• Harmonizing data from existing cohorts and registries to optimize research capabilities.

• Improving patient research partner involvement in research protocols.

[email protected]

The presence of fibromyalgia in patients who are undergoing treatment of spondyloarthritis (SpA) is associated with higher measures of disease activity and shorter duration of first-time treatment with tumor necrosis factor inhibitors, according to results of a study measuring the impact and prevalence of fibromyalgia coexisting with SpA.

The results confirm “that the existence of concomitant FM [fibromyalgia] in SpA might complicate the evaluation of treatment response and [suggest] that coexistence of FM should be carefully screened when initiating a TNFi [tumor necrosis factor inhibitor] and/or evaluating its treatment effect, especially in the presence of peripheral and/or enthesitic symptoms and in the presence of very severe disease activity and patient-reported scores,” wrote Dr. Natalia Bello and her colleagues at Cochin Hospital, Paris (Arthritis Res Ther. 2016 Feb 9;18:42. doi: 10.1186/s13075-016-0943-z).

©Zerbor/Thinkstock

They recruited patients from Cochin Hospital, a tertiary care facility, and its rheumatology department’s outpatient clinic. Rather than use the 1990 American College of Rheumatology (ACR) classification criteria of FM or the 2010 ACR or modified 2010 ACR diagnostic criteria, which were developed for research and classification purposes, the investigators diagnosed FM based on a score of 5 or 6 on the six-question, self-reported Fibromyalgia Rapid Screening Tool (FiRST), which has 90.5% sensitivity and 85.7% specificity for FM. Patients’ SpA diagnoses were made by their rheumatologists. Overall, 30% of the cohort was female and had a mean age of 43 years.

The overall FM prevalence in the cohort was 21.4% (42 of 196 patients) and did not differ significantly according to whether the patients met either the clinical or imaging ASAS (Assessment of Spondyloarthritis International Society) criteria (21.3% vs. 18.8%, respectively) or whether they did or did not fulfill the ASAS criteria (21.1% vs. 30.0%, respectively).

Previous studies have shown the prevalence of FM at 12.6%-15.0% in SpA patients. Classifying axial SpA based on the clinical arm criteria alone has been controversial, the investigators said, mainly because it does not require an objective sign of inflammation (abnormal C-reactive protein or presence of inflammatory lesions seen on MRI of the sacroiliac joint) or structural damage in the sacroiliac joint seen on pelvic radiographs. But at least in this study there was no difference in FM prevalence in regard to whether patients met either the imaging and clinical arms of the ASAS classification criteria for axial SpA or both.

The study, according to the best knowledge of the investigators, is the first “to evaluate the prevalence of FM in a population of patients with SpA with regard to the fulfillment of the ASAS classification criteria.”

FM patients had as expected a significantly higher rate of either history of depression, or use of psychotropic drugs or strong opioids, compared with patients without FM (67% vs. 35%; P less than .01). Rates of exposure to treatment with different drug types (nonsteroidal anti-inflammatory drugs or conventional antirheumatic disease-modifying drugs) did not differ between those with and without FM, but FM patients switched significantly more often from their first TNFi (15.2% vs. 4.0%) and used it for a significantly shorter mean duration (1.7 vs. 3.5 years). The percentage of patients still taking their first TNFi after 2 years also was significantly lower among FM patients (28.1% vs. 41.7%).

Within the entire cohort, FM patients more often had enthesitis (59.5% vs. 39.0%, P  =  .01), a higher total Bath Ankylosing Spondylitis Disease Activity Index (4.7 vs. 2.6; P less than .01), higher global visual analog scale (5.9 vs. 3.0; P less than .01), and higher Bath Ankylosing Spondylitis Functional Index (4.8 vs. 2.0; P less than .01).

The authors suggested that FM patients’ higher rates of peripheral symptoms and enthesitis may warrant the use of the FiRST questionnaire in clinical practice before starting a TNFi in SpA patients to detect potentially coexisting FM.

The authors had no conflicts of interest to declare.

[email protected]

The presence of fibromyalgia in patients who are undergoing treatment of spondyloarthritis (SpA) is associated with higher measures of disease activity and shorter duration of first-time treatment with tumor necrosis factor inhibitors, according to results of a study measuring the impact and prevalence of fibromyalgia coexisting with SpA.

The results confirm “that the existence of concomitant FM [fibromyalgia] in SpA might complicate the evaluation of treatment response and [suggest] that coexistence of FM should be carefully screened when initiating a TNFi [tumor necrosis factor inhibitor] and/or evaluating its treatment effect, especially in the presence of peripheral and/or enthesitic symptoms and in the presence of very severe disease activity and patient-reported scores,” wrote Dr. Natalia Bello and her colleagues at Cochin Hospital, Paris (Arthritis Res Ther. 2016 Feb 9;18:42. doi: 10.1186/s13075-016-0943-z).

©Zerbor/Thinkstock

They recruited patients from Cochin Hospital, a tertiary care facility, and its rheumatology department’s outpatient clinic. Rather than use the 1990 American College of Rheumatology (ACR) classification criteria of FM or the 2010 ACR or modified 2010 ACR diagnostic criteria, which were developed for research and classification purposes, the investigators diagnosed FM based on a score of 5 or 6 on the six-question, self-reported Fibromyalgia Rapid Screening Tool (FiRST), which has 90.5% sensitivity and 85.7% specificity for FM. Patients’ SpA diagnoses were made by their rheumatologists. Overall, 30% of the cohort was female and had a mean age of 43 years.

The overall FM prevalence in the cohort was 21.4% (42 of 196 patients) and did not differ significantly according to whether the patients met either the clinical or imaging ASAS (Assessment of Spondyloarthritis International Society) criteria (21.3% vs. 18.8%, respectively) or whether they did or did not fulfill the ASAS criteria (21.1% vs. 30.0%, respectively).

Previous studies have shown the prevalence of FM at 12.6%-15.0% in SpA patients. Classifying axial SpA based on the clinical arm criteria alone has been controversial, the investigators said, mainly because it does not require an objective sign of inflammation (abnormal C-reactive protein or presence of inflammatory lesions seen on MRI of the sacroiliac joint) or structural damage in the sacroiliac joint seen on pelvic radiographs. But at least in this study there was no difference in FM prevalence in regard to whether patients met either the imaging and clinical arms of the ASAS classification criteria for axial SpA or both.

The study, according to the best knowledge of the investigators, is the first “to evaluate the prevalence of FM in a population of patients with SpA with regard to the fulfillment of the ASAS classification criteria.”

FM patients had as expected a significantly higher rate of either history of depression, or use of psychotropic drugs or strong opioids, compared with patients without FM (67% vs. 35%; P less than .01). Rates of exposure to treatment with different drug types (nonsteroidal anti-inflammatory drugs or conventional antirheumatic disease-modifying drugs) did not differ between those with and without FM, but FM patients switched significantly more often from their first TNFi (15.2% vs. 4.0%) and used it for a significantly shorter mean duration (1.7 vs. 3.5 years). The percentage of patients still taking their first TNFi after 2 years also was significantly lower among FM patients (28.1% vs. 41.7%).

Within the entire cohort, FM patients more often had enthesitis (59.5% vs. 39.0%, P  =  .01), a higher total Bath Ankylosing Spondylitis Disease Activity Index (4.7 vs. 2.6; P less than .01), higher global visual analog scale (5.9 vs. 3.0; P less than .01), and higher Bath Ankylosing Spondylitis Functional Index (4.8 vs. 2.0; P less than .01).

The authors suggested that FM patients’ higher rates of peripheral symptoms and enthesitis may warrant the use of the FiRST questionnaire in clinical practice before starting a TNFi in SpA patients to detect potentially coexisting FM.

The authors had no conflicts of interest to declare.

[email protected]

The presence of fibromyalgia in patients who are undergoing treatment of spondyloarthritis (SpA) is associated with higher measures of disease activity and shorter duration of first-time treatment with tumor necrosis factor inhibitors, according to results of a study measuring the impact and prevalence of fibromyalgia coexisting with SpA.

The results confirm “that the existence of concomitant FM [fibromyalgia] in SpA might complicate the evaluation of treatment response and [suggest] that coexistence of FM should be carefully screened when initiating a TNFi [tumor necrosis factor inhibitor] and/or evaluating its treatment effect, especially in the presence of peripheral and/or enthesitic symptoms and in the presence of very severe disease activity and patient-reported scores,” wrote Dr. Natalia Bello and her colleagues at Cochin Hospital, Paris (Arthritis Res Ther. 2016 Feb 9;18:42. doi: 10.1186/s13075-016-0943-z).

©Zerbor/Thinkstock

They recruited patients from Cochin Hospital, a tertiary care facility, and its rheumatology department’s outpatient clinic. Rather than use the 1990 American College of Rheumatology (ACR) classification criteria of FM or the 2010 ACR or modified 2010 ACR diagnostic criteria, which were developed for research and classification purposes, the investigators diagnosed FM based on a score of 5 or 6 on the six-question, self-reported Fibromyalgia Rapid Screening Tool (FiRST), which has 90.5% sensitivity and 85.7% specificity for FM. Patients’ SpA diagnoses were made by their rheumatologists. Overall, 30% of the cohort was female and had a mean age of 43 years.

The overall FM prevalence in the cohort was 21.4% (42 of 196 patients) and did not differ significantly according to whether the patients met either the clinical or imaging ASAS (Assessment of Spondyloarthritis International Society) criteria (21.3% vs. 18.8%, respectively) or whether they did or did not fulfill the ASAS criteria (21.1% vs. 30.0%, respectively).

Previous studies have shown the prevalence of FM at 12.6%-15.0% in SpA patients. Classifying axial SpA based on the clinical arm criteria alone has been controversial, the investigators said, mainly because it does not require an objective sign of inflammation (abnormal C-reactive protein or presence of inflammatory lesions seen on MRI of the sacroiliac joint) or structural damage in the sacroiliac joint seen on pelvic radiographs. But at least in this study there was no difference in FM prevalence in regard to whether patients met either the imaging and clinical arms of the ASAS classification criteria for axial SpA or both.

The study, according to the best knowledge of the investigators, is the first “to evaluate the prevalence of FM in a population of patients with SpA with regard to the fulfillment of the ASAS classification criteria.”

FM patients had as expected a significantly higher rate of either history of depression, or use of psychotropic drugs or strong opioids, compared with patients without FM (67% vs. 35%; P less than .01). Rates of exposure to treatment with different drug types (nonsteroidal anti-inflammatory drugs or conventional antirheumatic disease-modifying drugs) did not differ between those with and without FM, but FM patients switched significantly more often from their first TNFi (15.2% vs. 4.0%) and used it for a significantly shorter mean duration (1.7 vs. 3.5 years). The percentage of patients still taking their first TNFi after 2 years also was significantly lower among FM patients (28.1% vs. 41.7%).

Within the entire cohort, FM patients more often had enthesitis (59.5% vs. 39.0%, P  =  .01), a higher total Bath Ankylosing Spondylitis Disease Activity Index (4.7 vs. 2.6; P less than .01), higher global visual analog scale (5.9 vs. 3.0; P less than .01), and higher Bath Ankylosing Spondylitis Functional Index (4.8 vs. 2.0; P less than .01).

The authors suggested that FM patients’ higher rates of peripheral symptoms and enthesitis may warrant the use of the FiRST questionnaire in clinical practice before starting a TNFi in SpA patients to detect potentially coexisting FM.

The authors had no conflicts of interest to declare.

[email protected]

The presence of rheumatoid arthritis in individuals who died from a myocardial infarction was associated with greater inflammatory burden at different levels of myocardial tissue than in those without the disease in a small, retrospective, case-control autopsy study.

“These findings support the hypothesis that RA [rheumatoid arthritis] patients are prone to develop more vulnerable plaques due to more inflammation in the coronary arteries, but also develop increased intramyocardial inflammation indicative of a higher risk of myocardial tissue damage post MI. This might not only explain the higher incidence of cardiovascular events in this population, but also the higher fatality rate after myocardial infarction,” wrote Dr. Inge A.M. van den Oever of the Amsterdam Rheumatology and Immunology Center and colleagues (Int J Cardiol. 2016 Feb 3. doi: 10.1016/j.ijcard.2016.02.065).

American Heart Association

The investigators took tissue samples from the infarcted left ventricle and microscopically determined infarct border area of five patients with RA and MI and five controls with MI but without RA. They found that RA patients had a greater burden of inflammatory cells in the adventitia of infarct-related epicardial coronary arteries, the intramyocardial vasculature, and the border area of the infarcted heart, compared with controls matched for age, sex, year of death, grade of stenosis, and infarct phase.

Specifically, the adventitial layer of the infarct-related epicardial coronary artery of RA patients had significantly more lymphocytes and mast cells. Intramyocardial arteries in infarct and infarct border areas of RA patients, compared with controls, showed significantly greater staining for advanced glycation end product N-epsilon-(carboxymethyl) lysine (CML), which is thought to reflect oxidative damage to cells, as well as noninfarcted tissues taken from the right ventricle.

The researchers included cases and controls from a postmortem tissue database of subjects who underwent autopsy within 24 hours after death at the VU University Medical Centre, Amsterdam, between January 1990 and December 2010.

The research was partly funded by a grant from the Dutch Society for Rheumatology. The authors had no conflicts of interest to declare.

[email protected]

The presence of rheumatoid arthritis in individuals who died from a myocardial infarction was associated with greater inflammatory burden at different levels of myocardial tissue than in those without the disease in a small, retrospective, case-control autopsy study.

“These findings support the hypothesis that RA [rheumatoid arthritis] patients are prone to develop more vulnerable plaques due to more inflammation in the coronary arteries, but also develop increased intramyocardial inflammation indicative of a higher risk of myocardial tissue damage post MI. This might not only explain the higher incidence of cardiovascular events in this population, but also the higher fatality rate after myocardial infarction,” wrote Dr. Inge A.M. van den Oever of the Amsterdam Rheumatology and Immunology Center and colleagues (Int J Cardiol. 2016 Feb 3. doi: 10.1016/j.ijcard.2016.02.065).

American Heart Association

The investigators took tissue samples from the infarcted left ventricle and microscopically determined infarct border area of five patients with RA and MI and five controls with MI but without RA. They found that RA patients had a greater burden of inflammatory cells in the adventitia of infarct-related epicardial coronary arteries, the intramyocardial vasculature, and the border area of the infarcted heart, compared with controls matched for age, sex, year of death, grade of stenosis, and infarct phase.

Specifically, the adventitial layer of the infarct-related epicardial coronary artery of RA patients had significantly more lymphocytes and mast cells. Intramyocardial arteries in infarct and infarct border areas of RA patients, compared with controls, showed significantly greater staining for advanced glycation end product N-epsilon-(carboxymethyl) lysine (CML), which is thought to reflect oxidative damage to cells, as well as noninfarcted tissues taken from the right ventricle.

The researchers included cases and controls from a postmortem tissue database of subjects who underwent autopsy within 24 hours after death at the VU University Medical Centre, Amsterdam, between January 1990 and December 2010.

The research was partly funded by a grant from the Dutch Society for Rheumatology. The authors had no conflicts of interest to declare.

[email protected]

The presence of rheumatoid arthritis in individuals who died from a myocardial infarction was associated with greater inflammatory burden at different levels of myocardial tissue than in those without the disease in a small, retrospective, case-control autopsy study.

“These findings support the hypothesis that RA [rheumatoid arthritis] patients are prone to develop more vulnerable plaques due to more inflammation in the coronary arteries, but also develop increased intramyocardial inflammation indicative of a higher risk of myocardial tissue damage post MI. This might not only explain the higher incidence of cardiovascular events in this population, but also the higher fatality rate after myocardial infarction,” wrote Dr. Inge A.M. van den Oever of the Amsterdam Rheumatology and Immunology Center and colleagues (Int J Cardiol. 2016 Feb 3. doi: 10.1016/j.ijcard.2016.02.065).

American Heart Association

The investigators took tissue samples from the infarcted left ventricle and microscopically determined infarct border area of five patients with RA and MI and five controls with MI but without RA. They found that RA patients had a greater burden of inflammatory cells in the adventitia of infarct-related epicardial coronary arteries, the intramyocardial vasculature, and the border area of the infarcted heart, compared with controls matched for age, sex, year of death, grade of stenosis, and infarct phase.

Specifically, the adventitial layer of the infarct-related epicardial coronary artery of RA patients had significantly more lymphocytes and mast cells. Intramyocardial arteries in infarct and infarct border areas of RA patients, compared with controls, showed significantly greater staining for advanced glycation end product N-epsilon-(carboxymethyl) lysine (CML), which is thought to reflect oxidative damage to cells, as well as noninfarcted tissues taken from the right ventricle.

The researchers included cases and controls from a postmortem tissue database of subjects who underwent autopsy within 24 hours after death at the VU University Medical Centre, Amsterdam, between January 1990 and December 2010.

The research was partly funded by a grant from the Dutch Society for Rheumatology. The authors had no conflicts of interest to declare.

[email protected]

New analyses of multiple sclerosis patients taking natalizumab reemphasize the need to monitor John Cunningham virus (JCV) seroconversion and the level of anti-JCV antibody titers via JCV index values, according to a study of a pair of German and French cohorts.

Longitudinal data available for 525 German patients and 711 French patients with relapsing-remitting multiple sclerosis (MS) revealed seroconversion rates of 8.5%-10.3% per year, seroprevalence increases of 5%-6% during 15-24 months of follow-up, and increases in JCV index values of 0.091 units (12.9%) per year, which “clearly support the facilitation [of progressive multifocal leukoencephalopathy (PML)] by treatment with natalizumab [Tysabri]” and are “at least 8 to 10 times as much as would be expected by age,” reported Nicholas Schwab, Ph.D., of the University of Münster (Germany) and his colleagues (Neurol Neuroimmunol Neuroinflamm. 2016;3:e195. doi: 10.1212/NXI.0000000000000195).

Of the longitudinally followed German patients, 186 (35.4%) were initially seropositive and 43 (12.7%) became seropositive during a mean follow-up duration of 14.8 months, or 10.3% per year. The group of 711 longitudinally followed French patients included 468 (65.8%) who were initially JCV positive. A total of 20 (8.2%) patients who were initially JCV negative seroconverted in the first year, and another 21 (8.6%) did so in the second year, for an overall rate of 8.5% per year.

A total of 525 patients had changes in the level of anti-JCV antibodies in serum (and therefore had changes in JCV index value) during the observation period. Patients with a JCV index value less than 0.4 (very low PML risk) declined from 65.1% to 61.3%, and those with values 0.4-0.9 (low risk) declined from 8.0% to 7.8%. The proportion grew from 4.6% to 5.9% for values 0.9-1.5 (medium risk) and from 22.3% to 25.0% for values greater than 1.5 (high risk). In addition to reflecting the patients’ change in serostatus, the change in PML risk levels “suggested that patients who changed serostatus directly presented with high anti-JCV antibody titers afterward, as the groups of low and medium risk did not grow substantially over time,” the researchers wrote.

A group of 201 patients who were followed over time after becoming seropositive had a mean JCV index value that rose significantly from 2.046 to 2.158 and was not attributable to aging. Rises in JCV index values of more than 30% over the course of 14.8 months occurred in 17% of the patients, compared with stable values in 80% and decreases of more than 30% in 3%. Altogether, the index value of all 201 patients rose by a mean of 0.091 units (12.9%) per year.

“Because as yet there are no studies on the influence of other treatments on JCV index values ... we cannot be certain that it was the treatment with natalizumab that led to the rising index values in our study,” the investigators wrote, although they noted that a recent study of more than 7,000 control patients with MS showed that the duration of non–natalizumab MS treatment did not influence JCV seroprevalence after adjustment for age, sex, and country of origin.

Also, even though the mean index value for JCV-positive patients was greater than 2, putting them in the highest PML risk category, the investigators noted that very few of these patients will ultimately develop PML, so “JCV serology should not be the only PML risk biomarker used in the stratification of patients treated with natalizumab.”

The study was funded by various German and French institutional and governmental grants. Many authors reported financial ties to companies marketing MS drugs, including Biogen, the manufacturer of natalizumab.

[email protected]

New analyses of multiple sclerosis patients taking natalizumab reemphasize the need to monitor John Cunningham virus (JCV) seroconversion and the level of anti-JCV antibody titers via JCV index values, according to a study of a pair of German and French cohorts.

Longitudinal data available for 525 German patients and 711 French patients with relapsing-remitting multiple sclerosis (MS) revealed seroconversion rates of 8.5%-10.3% per year, seroprevalence increases of 5%-6% during 15-24 months of follow-up, and increases in JCV index values of 0.091 units (12.9%) per year, which “clearly support the facilitation [of progressive multifocal leukoencephalopathy (PML)] by treatment with natalizumab [Tysabri]” and are “at least 8 to 10 times as much as would be expected by age,” reported Nicholas Schwab, Ph.D., of the University of Münster (Germany) and his colleagues (Neurol Neuroimmunol Neuroinflamm. 2016;3:e195. doi: 10.1212/NXI.0000000000000195).

Of the longitudinally followed German patients, 186 (35.4%) were initially seropositive and 43 (12.7%) became seropositive during a mean follow-up duration of 14.8 months, or 10.3% per year. The group of 711 longitudinally followed French patients included 468 (65.8%) who were initially JCV positive. A total of 20 (8.2%) patients who were initially JCV negative seroconverted in the first year, and another 21 (8.6%) did so in the second year, for an overall rate of 8.5% per year.

A total of 525 patients had changes in the level of anti-JCV antibodies in serum (and therefore had changes in JCV index value) during the observation period. Patients with a JCV index value less than 0.4 (very low PML risk) declined from 65.1% to 61.3%, and those with values 0.4-0.9 (low risk) declined from 8.0% to 7.8%. The proportion grew from 4.6% to 5.9% for values 0.9-1.5 (medium risk) and from 22.3% to 25.0% for values greater than 1.5 (high risk). In addition to reflecting the patients’ change in serostatus, the change in PML risk levels “suggested that patients who changed serostatus directly presented with high anti-JCV antibody titers afterward, as the groups of low and medium risk did not grow substantially over time,” the researchers wrote.

A group of 201 patients who were followed over time after becoming seropositive had a mean JCV index value that rose significantly from 2.046 to 2.158 and was not attributable to aging. Rises in JCV index values of more than 30% over the course of 14.8 months occurred in 17% of the patients, compared with stable values in 80% and decreases of more than 30% in 3%. Altogether, the index value of all 201 patients rose by a mean of 0.091 units (12.9%) per year.

“Because as yet there are no studies on the influence of other treatments on JCV index values ... we cannot be certain that it was the treatment with natalizumab that led to the rising index values in our study,” the investigators wrote, although they noted that a recent study of more than 7,000 control patients with MS showed that the duration of non–natalizumab MS treatment did not influence JCV seroprevalence after adjustment for age, sex, and country of origin.

Also, even though the mean index value for JCV-positive patients was greater than 2, putting them in the highest PML risk category, the investigators noted that very few of these patients will ultimately develop PML, so “JCV serology should not be the only PML risk biomarker used in the stratification of patients treated with natalizumab.”

The study was funded by various German and French institutional and governmental grants. Many authors reported financial ties to companies marketing MS drugs, including Biogen, the manufacturer of natalizumab.

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New analyses of multiple sclerosis patients taking natalizumab reemphasize the need to monitor John Cunningham virus (JCV) seroconversion and the level of anti-JCV antibody titers via JCV index values, according to a study of a pair of German and French cohorts.

Longitudinal data available for 525 German patients and 711 French patients with relapsing-remitting multiple sclerosis (MS) revealed seroconversion rates of 8.5%-10.3% per year, seroprevalence increases of 5%-6% during 15-24 months of follow-up, and increases in JCV index values of 0.091 units (12.9%) per year, which “clearly support the facilitation [of progressive multifocal leukoencephalopathy (PML)] by treatment with natalizumab [Tysabri]” and are “at least 8 to 10 times as much as would be expected by age,” reported Nicholas Schwab, Ph.D., of the University of Münster (Germany) and his colleagues (Neurol Neuroimmunol Neuroinflamm. 2016;3:e195. doi: 10.1212/NXI.0000000000000195).

Of the longitudinally followed German patients, 186 (35.4%) were initially seropositive and 43 (12.7%) became seropositive during a mean follow-up duration of 14.8 months, or 10.3% per year. The group of 711 longitudinally followed French patients included 468 (65.8%) who were initially JCV positive. A total of 20 (8.2%) patients who were initially JCV negative seroconverted in the first year, and another 21 (8.6%) did so in the second year, for an overall rate of 8.5% per year.

A total of 525 patients had changes in the level of anti-JCV antibodies in serum (and therefore had changes in JCV index value) during the observation period. Patients with a JCV index value less than 0.4 (very low PML risk) declined from 65.1% to 61.3%, and those with values 0.4-0.9 (low risk) declined from 8.0% to 7.8%. The proportion grew from 4.6% to 5.9% for values 0.9-1.5 (medium risk) and from 22.3% to 25.0% for values greater than 1.5 (high risk). In addition to reflecting the patients’ change in serostatus, the change in PML risk levels “suggested that patients who changed serostatus directly presented with high anti-JCV antibody titers afterward, as the groups of low and medium risk did not grow substantially over time,” the researchers wrote.

A group of 201 patients who were followed over time after becoming seropositive had a mean JCV index value that rose significantly from 2.046 to 2.158 and was not attributable to aging. Rises in JCV index values of more than 30% over the course of 14.8 months occurred in 17% of the patients, compared with stable values in 80% and decreases of more than 30% in 3%. Altogether, the index value of all 201 patients rose by a mean of 0.091 units (12.9%) per year.

“Because as yet there are no studies on the influence of other treatments on JCV index values ... we cannot be certain that it was the treatment with natalizumab that led to the rising index values in our study,” the investigators wrote, although they noted that a recent study of more than 7,000 control patients with MS showed that the duration of non–natalizumab MS treatment did not influence JCV seroprevalence after adjustment for age, sex, and country of origin.

Also, even though the mean index value for JCV-positive patients was greater than 2, putting them in the highest PML risk category, the investigators noted that very few of these patients will ultimately develop PML, so “JCV serology should not be the only PML risk biomarker used in the stratification of patients treated with natalizumab.”

The study was funded by various German and French institutional and governmental grants. Many authors reported financial ties to companies marketing MS drugs, including Biogen, the manufacturer of natalizumab.

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