Ted Bosworth

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.

When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.

The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.

Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.

In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.

These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.

This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”

The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.

The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.

According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.

“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”

There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.

“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.

He also emphasized that the advantage of PFO closure accrues over time.

“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.

Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

A bundle of blood cultures, broad-spectrum antibiotics, and intravenous fluid replacement reduces risk of in-hospital mortality among children with sepsis if all three forms of management are initiated within an hour, according to a cohort study published in JAMA.

invisioner/Thinkstock

Although published guidelines already recommend prompt initiation of these three elements of care, a mandate created in New York in 2013 called for these interventions to be initiated in children within 1 hour of sepsis recognition. The newly published cohort study shows a mortality benefit when this is done.

In the study, which evaluated the impact of the bundle as well as each of the components in 1,179 pediatric patients with sepsis treated at 54 hospitals, the risk-adjusted odds ratio of in-hospital mortality was 0.59 (P = .02) among patients receiving the mandated protocol, compared with those who did not.

When provided within 1 hour, none of the individual components of the bundles were associated with a significant reduction of risk-adjusted, in-hospital mortality by themselves. However, there were trends for benefit with blood cultures (OR, 0.73; P = .1) and broad-spectrum antibiotics (OR, 0.78; P = .18). There was no trend for administration of intravenous fluids (OR, 0.88; P = .56), for which the mandate specified 20 mL/kg.

Although 46.5% of patients received intravenous fluids, 62.8% received broad-spectrum antibiotics, and blood cultures were obtained in 67.7% of the children within 1 hour, only 24.9% were managed with the entire sepsis bundle. Across hospitals, the proportion of children completing the bundle ranged from 7.3% to 46.1%.

Bundle completion was more common in hospitals already treating a relatively high volume of pediatric patients and in those with pediatric specialty services, but the study authors noted that this was not a linear relationship. Rather, they called this association “hypothesis generating” and speculated that other factors might also be important.

The children in this cohort ranged in age from under 1 month to 17 years. Slightly more than half were aged 6 years or older and nearly one-third were older than 12 years. Nearly 45% had no comorbidities. Slightly more than one-third had a malignancy or were immunosuppressed.

None of the study authors reported any relevant financial relationships with industry.

SOURCE: Evans IVR et al. JAMA. 2018 Jul 24. doi:10.1001/jama.2018.9071.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.

AMSTERDAM – Rather than waiting for other drugs or immunotherapies to fail, an immediate up-front but time-limited course of an interleukin-1 receptor (IL-1R) antagonist induced rapid and sustained remissions in most children with systemic juvenile idiopathic arthritis (JIA), according to 5-year data presented at the European Congress of Rheumatology.

In the latest follow-up of a protocol first described in 2014, over 90% of patients still had inactive disease, 75% of whom were completely off therapy, reported Sebastiaan J. Vastert, MD, PhD, of the division of pediatrics at University Medical Center, Utrecht, the Netherlands.

AMSTERDAM – Rather than waiting for other drugs or immunotherapies to fail, an immediate up-front but time-limited course of an interleukin-1 receptor (IL-1R) antagonist induced rapid and sustained remissions in most children with systemic juvenile idiopathic arthritis (JIA), according to 5-year data presented at the European Congress of Rheumatology.

In the latest follow-up of a protocol first described in 2014, over 90% of patients still had inactive disease, 75% of whom were completely off therapy, reported Sebastiaan J. Vastert, MD, PhD, of the division of pediatrics at University Medical Center, Utrecht, the Netherlands.

AMSTERDAM – Rather than waiting for other drugs or immunotherapies to fail, an immediate up-front but time-limited course of an interleukin-1 receptor (IL-1R) antagonist induced rapid and sustained remissions in most children with systemic juvenile idiopathic arthritis (JIA), according to 5-year data presented at the European Congress of Rheumatology.

In the latest follow-up of a protocol first described in 2014, over 90% of patients still had inactive disease, 75% of whom were completely off therapy, reported Sebastiaan J. Vastert, MD, PhD, of the division of pediatrics at University Medical Center, Utrecht, the Netherlands.

AMSTERDAM – Etanercept does not appear to increase the risk of uveitis relative to methotrexate in children with juvenile idiopathic arthritis (JIA), according to a large retrospective cohort study presented at the EULAR 2018 Congress.

“When we added in a fully adjusted hazard ratio, it showed a lower risk in the development of uveitis in patients on etanercept [compared with methotrexate],” reported Rebecca Davies, a research assistant at the University of Manchester (England).

These data were characterized as reassuring for JIA patients being considered for etanercept, but Ms. Davies was cautious about suggesting that etanercept has a protective effect. Even though hazard ratios were calculated with propensity-adjusted Cox regression analyses, Ms. Davies believes the best interpretation of these data is that etanercept therapy is not likely to contribute significantly to the risk of uveitis.

The substantial differences between the comparator groups provide one reason to refrain from speculating that etanercept is protective against uveitis. The risk of uveitis is greater both in younger patients and in the first year after diagnosis. Patients in the etanercept group were older than patients in the methotrexate group and they started etanercept a longer time after the JIA diagnosis.

“The initiation of etanercept later in the disease may mean that more of these patients had already passed through the window of greatest risk,” Ms. Davies explained.

The data for this study were drawn from a British Society for Pediatric and Adolescent Rheumatology cohort registry. Confined to patients first starting as opposed to restarting therapy, 1,009 patients initiating etanercept were compared to 508 patients initiating methotrexate.

In addition to an older age (11 vs. 9 years) and disease duration at start of therapy (3 vs. 1 years), a lower proportion of patients in the etanercept group had a persistent oligoarthritis subtype (5% vs. 17%). During follow-up, there were 15 cases (0.15%) of uveitis in the etanercept group and 18 (3.5%) in the methotrexate group.

The crude incidence of uveitis was 0.6 per 100 patient-years for etanercept versus 2.4 per 100 patient-years for methotrexate, according to Ms. Davies. After adjustment for a broad number of variables, including age, gender, disease scores, disease duration, baseline steroid use, and the presence of comorbidities, there was still a 70% lower risk of uveitis among those treated with etanercept (hazard ratio 0.30; 95% confidence interval, 0.1-0.9).

The low relative rate of uveitis after starting etanercept is discordant with several previous studies, according to Ms. Davies. In two retrospective studies conducted in the United States and one in Canada, etanercept treatment was associated with higher rates of uveitis than other tumor necrosis factor inhibitors. In a German study, etanercept was associated with a higher risk of uveitis than that of methotrexate.

Although a highly effective anti-inflammatory agent such as etanercept might be expected to have a protective effect against uveitis, at least relative to methotrexate, Ms. Davies suggested that the previous reports of potential causal association and the limitations of this retrospective analysis require a more cautious interpretation.

“It is possible that those considered to be at high risk of developing uveitis were kept away from etanercept,” said Ms. Davis, providing one of several explanations why skepticism is needed in regard to assuming uveitis protection from etanercept.

SOURCE: EULAR 2018 Congress. Abstract OP0351.

AMSTERDAM – Etanercept does not appear to increase the risk of uveitis relative to methotrexate in children with juvenile idiopathic arthritis (JIA), according to a large retrospective cohort study presented at the EULAR 2018 Congress.

“When we added in a fully adjusted hazard ratio, it showed a lower risk in the development of uveitis in patients on etanercept [compared with methotrexate],” reported Rebecca Davies, a research assistant at the University of Manchester (England).

These data were characterized as reassuring for JIA patients being considered for etanercept, but Ms. Davies was cautious about suggesting that etanercept has a protective effect. Even though hazard ratios were calculated with propensity-adjusted Cox regression analyses, Ms. Davies believes the best interpretation of these data is that etanercept therapy is not likely to contribute significantly to the risk of uveitis.

The substantial differences between the comparator groups provide one reason to refrain from speculating that etanercept is protective against uveitis. The risk of uveitis is greater both in younger patients and in the first year after diagnosis. Patients in the etanercept group were older than patients in the methotrexate group and they started etanercept a longer time after the JIA diagnosis.

“The initiation of etanercept later in the disease may mean that more of these patients had already passed through the window of greatest risk,” Ms. Davies explained.

The data for this study were drawn from a British Society for Pediatric and Adolescent Rheumatology cohort registry. Confined to patients first starting as opposed to restarting therapy, 1,009 patients initiating etanercept were compared to 508 patients initiating methotrexate.

In addition to an older age (11 vs. 9 years) and disease duration at start of therapy (3 vs. 1 years), a lower proportion of patients in the etanercept group had a persistent oligoarthritis subtype (5% vs. 17%). During follow-up, there were 15 cases (0.15%) of uveitis in the etanercept group and 18 (3.5%) in the methotrexate group.

The crude incidence of uveitis was 0.6 per 100 patient-years for etanercept versus 2.4 per 100 patient-years for methotrexate, according to Ms. Davies. After adjustment for a broad number of variables, including age, gender, disease scores, disease duration, baseline steroid use, and the presence of comorbidities, there was still a 70% lower risk of uveitis among those treated with etanercept (hazard ratio 0.30; 95% confidence interval, 0.1-0.9).

The low relative rate of uveitis after starting etanercept is discordant with several previous studies, according to Ms. Davies. In two retrospective studies conducted in the United States and one in Canada, etanercept treatment was associated with higher rates of uveitis than other tumor necrosis factor inhibitors. In a German study, etanercept was associated with a higher risk of uveitis than that of methotrexate.

Although a highly effective anti-inflammatory agent such as etanercept might be expected to have a protective effect against uveitis, at least relative to methotrexate, Ms. Davies suggested that the previous reports of potential causal association and the limitations of this retrospective analysis require a more cautious interpretation.

“It is possible that those considered to be at high risk of developing uveitis were kept away from etanercept,” said Ms. Davis, providing one of several explanations why skepticism is needed in regard to assuming uveitis protection from etanercept.

SOURCE: EULAR 2018 Congress. Abstract OP0351.

AMSTERDAM – Etanercept does not appear to increase the risk of uveitis relative to methotrexate in children with juvenile idiopathic arthritis (JIA), according to a large retrospective cohort study presented at the EULAR 2018 Congress.

“When we added in a fully adjusted hazard ratio, it showed a lower risk in the development of uveitis in patients on etanercept [compared with methotrexate],” reported Rebecca Davies, a research assistant at the University of Manchester (England).

These data were characterized as reassuring for JIA patients being considered for etanercept, but Ms. Davies was cautious about suggesting that etanercept has a protective effect. Even though hazard ratios were calculated with propensity-adjusted Cox regression analyses, Ms. Davies believes the best interpretation of these data is that etanercept therapy is not likely to contribute significantly to the risk of uveitis.

The substantial differences between the comparator groups provide one reason to refrain from speculating that etanercept is protective against uveitis. The risk of uveitis is greater both in younger patients and in the first year after diagnosis. Patients in the etanercept group were older than patients in the methotrexate group and they started etanercept a longer time after the JIA diagnosis.

“The initiation of etanercept later in the disease may mean that more of these patients had already passed through the window of greatest risk,” Ms. Davies explained.

The data for this study were drawn from a British Society for Pediatric and Adolescent Rheumatology cohort registry. Confined to patients first starting as opposed to restarting therapy, 1,009 patients initiating etanercept were compared to 508 patients initiating methotrexate.

In addition to an older age (11 vs. 9 years) and disease duration at start of therapy (3 vs. 1 years), a lower proportion of patients in the etanercept group had a persistent oligoarthritis subtype (5% vs. 17%). During follow-up, there were 15 cases (0.15%) of uveitis in the etanercept group and 18 (3.5%) in the methotrexate group.

The crude incidence of uveitis was 0.6 per 100 patient-years for etanercept versus 2.4 per 100 patient-years for methotrexate, according to Ms. Davies. After adjustment for a broad number of variables, including age, gender, disease scores, disease duration, baseline steroid use, and the presence of comorbidities, there was still a 70% lower risk of uveitis among those treated with etanercept (hazard ratio 0.30; 95% confidence interval, 0.1-0.9).

The low relative rate of uveitis after starting etanercept is discordant with several previous studies, according to Ms. Davies. In two retrospective studies conducted in the United States and one in Canada, etanercept treatment was associated with higher rates of uveitis than other tumor necrosis factor inhibitors. In a German study, etanercept was associated with a higher risk of uveitis than that of methotrexate.

Although a highly effective anti-inflammatory agent such as etanercept might be expected to have a protective effect against uveitis, at least relative to methotrexate, Ms. Davies suggested that the previous reports of potential causal association and the limitations of this retrospective analysis require a more cautious interpretation.

“It is possible that those considered to be at high risk of developing uveitis were kept away from etanercept,” said Ms. Davis, providing one of several explanations why skepticism is needed in regard to assuming uveitis protection from etanercept.

SOURCE: EULAR 2018 Congress. Abstract OP0351.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.

AMSTERDAM – In patients with autoimmune diseases, cancer treatment with checkpoint inhibitor immunotherapy increases the risk of flares, but these flares are associated with improved cancer outcomes, according to a multicenter, retrospective study presented at the European Congress of Rheumatology.

“Survival was longer in patients who experienced a flare of their preexisting autoimmune disease or any other immune-related adverse event, but this gain was lost if an immunosuppressive therapy was used,” reported Alice Tison, a resident in rheumatology at the Centre Hospitalier Universitaire, Brest, France.

These were some of the mixed messages from this evaluation, which involved 112 patients with preexisting autoimmune disease (PAD) whose data were collected from 11 tertiary care centers in France. Of the cases of PAD represented, the majority involved joint diseases, including psoriatic arthritis (28%), rheumatoid arthritis (18%), and spondyloarthritis (4.5%). However, other types of PAD, including inflammatory bowel disease (13%), were included in the series.

Only 33% of the patients had active disease at the time that checkpoint inhibitor therapy was initiated, and only 21% were taking an immunosuppressive therapy for their disease. Of those on therapy, the majority were taking steroids, but about a third of those on therapy were taking a disease-modifying antirheumatic drug, such as methotrexate.

With the initiation of checkpoint inhibitors, which were offered primarily for the treatment of melanoma (59%) and non–small cell lung cancer (36%), 42% of patients with PAD developed a disease flare. Of these, 30% were considered severe. Other immune-related events not considered related to the underlying disease, such as colitis, were also observed but at rates not clearly different than those observed in patients without PAD.

The activity of checkpoint inhibitors did not appear to be different than that observed in non-PAD patients. For example, the overall response rate was 48% in those with melanoma and 54% in those with non–small cell lung cancer. After a median of 8 months of follow-up, the median progression-free survival was 12.4 months and 9.7 months for the two diseases, respectively. Median overall survival had not been reached in either disease.

However, those with a flare or another immune-related adverse event had significantly better progression-free survival (P = .016) and overall survival (P = .004) when compared with those who did not flare or have an immune-related adverse event. According to Ms. Tison, this has been reported before, but a more surprising finding was that the gain in progression-free survival and overall survival was lost in those treated with an immunosuppressive drug.

Even though non-PAD patients commonly receive steroids for immune-related adverse events such as colitis, the loss of benefit in PAD patients who received immunosuppressive therapies may be caused by, at least in part, cross-reactivity between tumor antigens and autoantigens, Ms. Tison speculated.

Ms. Tison was cautious in drawing conclusions about specific strategies to optimize benefits from checkpoint inhibitors in PAD based on this limited series of patients. However, she did suggest that discontinuation of immunosuppressive therapies prior to initiating checkpoint inhibitors may be prudent in PAD patients, particularly those with inactive disease.

Overall, she emphasized that checkpoint inhibitors “have revolutionized the management of several cancers” and should not be denied to PAD patients who are otherwise appropriate candidates. Although flares are common, more than half of PAD patients in this series did not flare and flares were mild to moderate in most of those who did.

“The response to checkpoint inhibitors in PAD patients is good,” Ms. Tison advised. For those who do flare, “we need prospective studies to understand which strategies provide a good balance of benefit to risk” for cancer immunotherapy and for the options to manage immune-related adverse events.

The study was not industry funded. Ms. Tison reported no potential conflicts of interest.

SOURCE: Tison A et al. Ann Rheum Dis. 2018;77(Suppl 2):147. EULAR Congress 2018, Abstract OP0196.

AMSTERDAM – Opioids cannot be justified for the routine treatment for musculoskeletal pain because risks outweigh benefits, according to a detailed review of published studies presented at the European Congress of Rheumatology.

“There is very little evidence of benefit for the long-term management of nonmalignant pain, but very good evidence for harm,” reported Blair Smith, MD, head of the population health sciences division, University of Dundee (Scotland).

Ted Bosworth/MDedge News

In the treatment of musculoskeletal pain, the goals are increased function and quality of life, rather than complete relief of pain, according to Dr. Smith. On this basis, opioids are not an appropriate routine therapy. He reported that pain relief is not well documented, while side effects such as sedation, dizziness, and constipation, are likely to be counterproductive to improved outcomes.

There is no absolute contraindication for opioids in the control of chronic musculoskeletal pain, but Dr. Smith’s summary of the data led him to conclude that they should be used judiciously and “only for carefully selected patients.”

Of the many studies he reviewed to draw this conclusion, one of the most recent was identified as the most persuasive. Published earlier this year, the SPACE study is “the first good-quality study of long-term opioid use” in patients with musculoskeletal complaints. It was negative.

“The pain intensity at the end of 12 months of treatment was slightly but significantly worse among those randomized to opioids,” reported Dr. Smith. “There was no difference in patient function, but there was an increased risk of adverse events.”

In the SPACE study, 240 patients with moderate to severe chronic back pain or hip or knee osteoarthritis were randomized to opioid or nonopioid pain management. In the nonopioid group, the first therapeutic step was acetaminophen, but medications could be changed, added, or adjusted within both groups to improve patient response.

At the end of 12 months, a lack of benefit on both pain control and functional improvement from opioids relative to nonopioid treatment was accompanied by a higher rate of adverse effects. This led the authors to conclude that opioids are not supported for musculoskeletal pain.

Not all the evidence argues against opioids for noncancer pain management, according to Dr. Smith, but he emphasized that those who support use of opioids do so for pain control only. They do not confirm an advantage for function and quality of life, which he suggested are the key endpoints. For example, a 2010 Cochrane review concluded from a systematic literature review that there is “weak evidence” for pain relief but inconclusive evidence of an improvement in functioning and quality of life.

Other investigators have drawn the same conclusion, according to Dr. Smith. He cited a statement from the International Association for Study of Pain that advises, “Caution should be used for prescribing opioids for chronic pain.” Although this statement was not specific to musculoskeletal pain, the IASP does specify that pain medications should be employed “to promote increased function and improved quality of life rather than complete relief of pain,” according to Dr. Smith.

Opioid prescriptions for chronic pain have been increasing in Europe as they have in the United States, but Dr. Smith indicated that opioids, if used at all, should be prescribed for very short periods and for very specific goals, particularly improvement in function.

“Probably most important for my [primary care] colleagues, patients prescribed opioids should be evaluated early and frequently to gauge benefit,” Dr. Smith said. Although he believes pain control is an important and worthwhile goal, it must be approached within the context of improved well-being rather than as an isolated endpoint.
 

SOURCE: Smith B et al. EULAR 2018, Abstract No. SP0073.

AMSTERDAM – Opioids cannot be justified for the routine treatment for musculoskeletal pain because risks outweigh benefits, according to a detailed review of published studies presented at the European Congress of Rheumatology.

“There is very little evidence of benefit for the long-term management of nonmalignant pain, but very good evidence for harm,” reported Blair Smith, MD, head of the population health sciences division, University of Dundee (Scotland).

Ted Bosworth/MDedge News

In the treatment of musculoskeletal pain, the goals are increased function and quality of life, rather than complete relief of pain, according to Dr. Smith. On this basis, opioids are not an appropriate routine therapy. He reported that pain relief is not well documented, while side effects such as sedation, dizziness, and constipation, are likely to be counterproductive to improved outcomes.

There is no absolute contraindication for opioids in the control of chronic musculoskeletal pain, but Dr. Smith’s summary of the data led him to conclude that they should be used judiciously and “only for carefully selected patients.”

Of the many studies he reviewed to draw this conclusion, one of the most recent was identified as the most persuasive. Published earlier this year, the SPACE study is “the first good-quality study of long-term opioid use” in patients with musculoskeletal complaints. It was negative.

“The pain intensity at the end of 12 months of treatment was slightly but significantly worse among those randomized to opioids,” reported Dr. Smith. “There was no difference in patient function, but there was an increased risk of adverse events.”

In the SPACE study, 240 patients with moderate to severe chronic back pain or hip or knee osteoarthritis were randomized to opioid or nonopioid pain management. In the nonopioid group, the first therapeutic step was acetaminophen, but medications could be changed, added, or adjusted within both groups to improve patient response.

At the end of 12 months, a lack of benefit on both pain control and functional improvement from opioids relative to nonopioid treatment was accompanied by a higher rate of adverse effects. This led the authors to conclude that opioids are not supported for musculoskeletal pain.

Not all the evidence argues against opioids for noncancer pain management, according to Dr. Smith, but he emphasized that those who support use of opioids do so for pain control only. They do not confirm an advantage for function and quality of life, which he suggested are the key endpoints. For example, a 2010 Cochrane review concluded from a systematic literature review that there is “weak evidence” for pain relief but inconclusive evidence of an improvement in functioning and quality of life.

Other investigators have drawn the same conclusion, according to Dr. Smith. He cited a statement from the International Association for Study of Pain that advises, “Caution should be used for prescribing opioids for chronic pain.” Although this statement was not specific to musculoskeletal pain, the IASP does specify that pain medications should be employed “to promote increased function and improved quality of life rather than complete relief of pain,” according to Dr. Smith.

Opioid prescriptions for chronic pain have been increasing in Europe as they have in the United States, but Dr. Smith indicated that opioids, if used at all, should be prescribed for very short periods and for very specific goals, particularly improvement in function.

“Probably most important for my [primary care] colleagues, patients prescribed opioids should be evaluated early and frequently to gauge benefit,” Dr. Smith said. Although he believes pain control is an important and worthwhile goal, it must be approached within the context of improved well-being rather than as an isolated endpoint.
 

SOURCE: Smith B et al. EULAR 2018, Abstract No. SP0073.

AMSTERDAM – Opioids cannot be justified for the routine treatment for musculoskeletal pain because risks outweigh benefits, according to a detailed review of published studies presented at the European Congress of Rheumatology.

“There is very little evidence of benefit for the long-term management of nonmalignant pain, but very good evidence for harm,” reported Blair Smith, MD, head of the population health sciences division, University of Dundee (Scotland).

Ted Bosworth/MDedge News

In the treatment of musculoskeletal pain, the goals are increased function and quality of life, rather than complete relief of pain, according to Dr. Smith. On this basis, opioids are not an appropriate routine therapy. He reported that pain relief is not well documented, while side effects such as sedation, dizziness, and constipation, are likely to be counterproductive to improved outcomes.

There is no absolute contraindication for opioids in the control of chronic musculoskeletal pain, but Dr. Smith’s summary of the data led him to conclude that they should be used judiciously and “only for carefully selected patients.”

Of the many studies he reviewed to draw this conclusion, one of the most recent was identified as the most persuasive. Published earlier this year, the SPACE study is “the first good-quality study of long-term opioid use” in patients with musculoskeletal complaints. It was negative.

“The pain intensity at the end of 12 months of treatment was slightly but significantly worse among those randomized to opioids,” reported Dr. Smith. “There was no difference in patient function, but there was an increased risk of adverse events.”

In the SPACE study, 240 patients with moderate to severe chronic back pain or hip or knee osteoarthritis were randomized to opioid or nonopioid pain management. In the nonopioid group, the first therapeutic step was acetaminophen, but medications could be changed, added, or adjusted within both groups to improve patient response.

At the end of 12 months, a lack of benefit on both pain control and functional improvement from opioids relative to nonopioid treatment was accompanied by a higher rate of adverse effects. This led the authors to conclude that opioids are not supported for musculoskeletal pain.

Not all the evidence argues against opioids for noncancer pain management, according to Dr. Smith, but he emphasized that those who support use of opioids do so for pain control only. They do not confirm an advantage for function and quality of life, which he suggested are the key endpoints. For example, a 2010 Cochrane review concluded from a systematic literature review that there is “weak evidence” for pain relief but inconclusive evidence of an improvement in functioning and quality of life.

Other investigators have drawn the same conclusion, according to Dr. Smith. He cited a statement from the International Association for Study of Pain that advises, “Caution should be used for prescribing opioids for chronic pain.” Although this statement was not specific to musculoskeletal pain, the IASP does specify that pain medications should be employed “to promote increased function and improved quality of life rather than complete relief of pain,” according to Dr. Smith.

Opioid prescriptions for chronic pain have been increasing in Europe as they have in the United States, but Dr. Smith indicated that opioids, if used at all, should be prescribed for very short periods and for very specific goals, particularly improvement in function.

“Probably most important for my [primary care] colleagues, patients prescribed opioids should be evaluated early and frequently to gauge benefit,” Dr. Smith said. Although he believes pain control is an important and worthwhile goal, it must be approached within the context of improved well-being rather than as an isolated endpoint.
 

SOURCE: Smith B et al. EULAR 2018, Abstract No. SP0073.

AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.

“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.

SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.

AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.

“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.

SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.

AMSTERDAM – In patients with psoriatic arthritis (PsA), new evidence suggests selection of biologic disease-modifying antirheumatic drugs (bDMARDs) might be individualized by T-helper cell phenotype to improve disease control, according to the results of a study presented at the European Congress of Rheumatology.

“Our findings suggest a potential for precision medicine in patients with psoriatic arthritis,” reported Ippei Miyagawa, MD, of the University of Occupational and Environmental Health in Kitakyushu, Japan.

SOURCE: Miyagawa I et al. Ann Rheum Dis. 2018;77(Suppl 2):206-7. EULAR Congress 2018, Abstract OP0321.

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307