Ted Bosworth

MADRID – In axial spondyloarthritis patients who discontinue a tumor necrosis factor inhibitor (TNFi), there does not appear to be any advantage for using the anti–interleukin-17 biologic secukinumab over a different tumor necrosis factor inhibitor for next therapy, according to an analysis presented at the European Congress of Rheumatology.

Ted Bosworth/MDedge News

“Switching to secukinumab [Cosentyx] might even be inferior in many patients,” according to Adrian Ciurea, MD, of the clinic for rheumatology at University Hospital Zürich.

This conclusion was reached in a retrospective analysis of axial spondyloarthritis (axSpA) patients enrolled in the Swiss Clinical Quality Management Cohort. Although Dr. Ciurea said that a prospective trial is needed to confirm the findings, this study was conducted because there have been, up until now, “no data to choose between options” to guide this choice.

In this study of 382 axSpA patients who were candidates for a new biologic after discontinuing a previous TNFi, 275 were started on a different TNFi and 107 were started on secukinumab. Although about 60% of patients in both groups were HLAB27-positive, there were many other characteristics, including those related to disease severity, that were different, Dr. Ciurea acknowledged.

Specifically, the proportion of patients starting secukinumab treated with two or more TNF inhibitors was greater than that of patients switching to another TNFi (77.6% vs. 37.8%; P less than .001). In addition, patients in the secukinumab group had a higher baseline disease activity, more enthesitis, and greater axial impairment.

These were reflected in higher average Bath Ankylosing Spondylitis Disease Activity Index scores (6.1 vs. 4.8; P less than .001) as well as other baseline clinical scoring methods, such as the Bath Ankylosing Spondylitis Functional Index and the Maastricht Ankylosing Spondylitis Enthesitis Score.

However, baseline high-sensitivity C-reactive protein levels, number of swollen joints, or years of symptom duration were not significantly different between the groups, although all were numerically higher in the secukinumab group. The proportion of patients with uveitis was higher in the TNFi group. About 70% of patients in both groups had discontinued their prior TNFi for inadequate response.

For the primary assessment of drug survival on the new therapy, the median time was 1.1 years in the secukinumab group and 2.0 years in the group switched to a new TNFi, without adjustment for baseline characteristics and disease severity. After risk adjustment, this difference was no statistically significant.

“There was an interaction with gender, indicating a significantly higher risk of discontinuing secukinumab than a new TNFi in men,” according to Dr. Ciurea. This was not seen in women.

Previous studies have shown the response rate to a second TNFi is typically lower than for an initial TNFi therapy. Previous studies have also shown that response to secukinumab is lower in patients with previous TNFi experience than in those who are naive to biologics, Dr. Ciurea said. This analysis suggests that the likelihood of sustained disease control is not greater in TNFi-experienced patients who start secukinumab relative to a different TNFi.

When asked if the data had been analyzed to compare response in patients exposed to only one prior TNFi, Dr. Ciurea replied that this could not be done because the sample size was too small.

Although Dr. Ciurea acknowledged the limitations of retrospective studies with risk adjustments, he concluded that there does not appear to be an advantage for initiating secukinumab over starting a different TNFi in axSpA patients who require a switch from their current TNFi,

Even though he said that this is the first study to address this question objectively, Dr. Ciurea said, “A sufficiently powered, prospective, head-to-head trial is needed.”

Dr. Ciurea reported multiple financial relationships with pharmaceutical companies but received no funding for this study.

SOURCE: Tellenbach C et al. Ann Rheum Dis. 2019;78(Suppl 2):197. Abstract OPO237, doi: 10.1136/annrheumdis-2019-eular.2427

MADRID – In axial spondyloarthritis patients who discontinue a tumor necrosis factor inhibitor (TNFi), there does not appear to be any advantage for using the anti–interleukin-17 biologic secukinumab over a different tumor necrosis factor inhibitor for next therapy, according to an analysis presented at the European Congress of Rheumatology.

Ted Bosworth/MDedge News

“Switching to secukinumab [Cosentyx] might even be inferior in many patients,” according to Adrian Ciurea, MD, of the clinic for rheumatology at University Hospital Zürich.

This conclusion was reached in a retrospective analysis of axial spondyloarthritis (axSpA) patients enrolled in the Swiss Clinical Quality Management Cohort. Although Dr. Ciurea said that a prospective trial is needed to confirm the findings, this study was conducted because there have been, up until now, “no data to choose between options” to guide this choice.

In this study of 382 axSpA patients who were candidates for a new biologic after discontinuing a previous TNFi, 275 were started on a different TNFi and 107 were started on secukinumab. Although about 60% of patients in both groups were HLAB27-positive, there were many other characteristics, including those related to disease severity, that were different, Dr. Ciurea acknowledged.

Specifically, the proportion of patients starting secukinumab treated with two or more TNF inhibitors was greater than that of patients switching to another TNFi (77.6% vs. 37.8%; P less than .001). In addition, patients in the secukinumab group had a higher baseline disease activity, more enthesitis, and greater axial impairment.

These were reflected in higher average Bath Ankylosing Spondylitis Disease Activity Index scores (6.1 vs. 4.8; P less than .001) as well as other baseline clinical scoring methods, such as the Bath Ankylosing Spondylitis Functional Index and the Maastricht Ankylosing Spondylitis Enthesitis Score.

However, baseline high-sensitivity C-reactive protein levels, number of swollen joints, or years of symptom duration were not significantly different between the groups, although all were numerically higher in the secukinumab group. The proportion of patients with uveitis was higher in the TNFi group. About 70% of patients in both groups had discontinued their prior TNFi for inadequate response.

For the primary assessment of drug survival on the new therapy, the median time was 1.1 years in the secukinumab group and 2.0 years in the group switched to a new TNFi, without adjustment for baseline characteristics and disease severity. After risk adjustment, this difference was no statistically significant.

“There was an interaction with gender, indicating a significantly higher risk of discontinuing secukinumab than a new TNFi in men,” according to Dr. Ciurea. This was not seen in women.

Previous studies have shown the response rate to a second TNFi is typically lower than for an initial TNFi therapy. Previous studies have also shown that response to secukinumab is lower in patients with previous TNFi experience than in those who are naive to biologics, Dr. Ciurea said. This analysis suggests that the likelihood of sustained disease control is not greater in TNFi-experienced patients who start secukinumab relative to a different TNFi.

When asked if the data had been analyzed to compare response in patients exposed to only one prior TNFi, Dr. Ciurea replied that this could not be done because the sample size was too small.

Although Dr. Ciurea acknowledged the limitations of retrospective studies with risk adjustments, he concluded that there does not appear to be an advantage for initiating secukinumab over starting a different TNFi in axSpA patients who require a switch from their current TNFi,

Even though he said that this is the first study to address this question objectively, Dr. Ciurea said, “A sufficiently powered, prospective, head-to-head trial is needed.”

Dr. Ciurea reported multiple financial relationships with pharmaceutical companies but received no funding for this study.

SOURCE: Tellenbach C et al. Ann Rheum Dis. 2019;78(Suppl 2):197. Abstract OPO237, doi: 10.1136/annrheumdis-2019-eular.2427

MADRID – In axial spondyloarthritis patients who discontinue a tumor necrosis factor inhibitor (TNFi), there does not appear to be any advantage for using the anti–interleukin-17 biologic secukinumab over a different tumor necrosis factor inhibitor for next therapy, according to an analysis presented at the European Congress of Rheumatology.

Ted Bosworth/MDedge News

“Switching to secukinumab [Cosentyx] might even be inferior in many patients,” according to Adrian Ciurea, MD, of the clinic for rheumatology at University Hospital Zürich.

This conclusion was reached in a retrospective analysis of axial spondyloarthritis (axSpA) patients enrolled in the Swiss Clinical Quality Management Cohort. Although Dr. Ciurea said that a prospective trial is needed to confirm the findings, this study was conducted because there have been, up until now, “no data to choose between options” to guide this choice.

In this study of 382 axSpA patients who were candidates for a new biologic after discontinuing a previous TNFi, 275 were started on a different TNFi and 107 were started on secukinumab. Although about 60% of patients in both groups were HLAB27-positive, there were many other characteristics, including those related to disease severity, that were different, Dr. Ciurea acknowledged.

Specifically, the proportion of patients starting secukinumab treated with two or more TNF inhibitors was greater than that of patients switching to another TNFi (77.6% vs. 37.8%; P less than .001). In addition, patients in the secukinumab group had a higher baseline disease activity, more enthesitis, and greater axial impairment.

These were reflected in higher average Bath Ankylosing Spondylitis Disease Activity Index scores (6.1 vs. 4.8; P less than .001) as well as other baseline clinical scoring methods, such as the Bath Ankylosing Spondylitis Functional Index and the Maastricht Ankylosing Spondylitis Enthesitis Score.

However, baseline high-sensitivity C-reactive protein levels, number of swollen joints, or years of symptom duration were not significantly different between the groups, although all were numerically higher in the secukinumab group. The proportion of patients with uveitis was higher in the TNFi group. About 70% of patients in both groups had discontinued their prior TNFi for inadequate response.

For the primary assessment of drug survival on the new therapy, the median time was 1.1 years in the secukinumab group and 2.0 years in the group switched to a new TNFi, without adjustment for baseline characteristics and disease severity. After risk adjustment, this difference was no statistically significant.

“There was an interaction with gender, indicating a significantly higher risk of discontinuing secukinumab than a new TNFi in men,” according to Dr. Ciurea. This was not seen in women.

Previous studies have shown the response rate to a second TNFi is typically lower than for an initial TNFi therapy. Previous studies have also shown that response to secukinumab is lower in patients with previous TNFi experience than in those who are naive to biologics, Dr. Ciurea said. This analysis suggests that the likelihood of sustained disease control is not greater in TNFi-experienced patients who start secukinumab relative to a different TNFi.

When asked if the data had been analyzed to compare response in patients exposed to only one prior TNFi, Dr. Ciurea replied that this could not be done because the sample size was too small.

Although Dr. Ciurea acknowledged the limitations of retrospective studies with risk adjustments, he concluded that there does not appear to be an advantage for initiating secukinumab over starting a different TNFi in axSpA patients who require a switch from their current TNFi,

Even though he said that this is the first study to address this question objectively, Dr. Ciurea said, “A sufficiently powered, prospective, head-to-head trial is needed.”

Dr. Ciurea reported multiple financial relationships with pharmaceutical companies but received no funding for this study.

SOURCE: Tellenbach C et al. Ann Rheum Dis. 2019;78(Suppl 2):197. Abstract OPO237, doi: 10.1136/annrheumdis-2019-eular.2427

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

Although guideline recommended, treating children in shock with a bolus of saline or albumin fluid imposes counterproductive effects on respiratory and neurologic function, ultimately increasing risk of death, according to a detailed analysis of available data, including a randomized trial.

Several sets of guidelines for resuscitation of patients in shock have advocated volume expansion with bolus intravenous fluid, but that recommendation was based on expected physiologic benefits not a randomized trial. The only randomized trial associated this approach showed increased mortality, and a new analysis of these and other data appears to explain why.

According to the findings of a study lead by Michael Levin, MD, of the department of medicine at Imperial College London and colleagues, “volume resuscitation is associated with deterioration of respiratory function and neurological function in some patients.” Their study was published in Lancet Respiratory Medicine. The authors stated that saline-induced hyperchloremic acidosis appears to have been “a major contributor” to the observed increase in adverse outcomes.

The key take home message is that “normal saline and other unbuffered crystalloid solutions should be avoided in resuscitating seriously ill patients,” according to the authors, who believe the findings might be relevant to adults as well as children.

The controversy about the role of volume expansion for management of shock was ignited by a 2011 trial called FEAST (N Engl J Med. 2011;364:2483-95). That trial, which randomized African children with severe febrile illness to a bolus of 20-40 mg of 5% albumin solution, a bolus of 0.9% saline solution, or no bolus, was halted early when 48-hour mortality data showed a lower death rate in the no bolus group (7.3%) than either the albumin (10.6%) or saline (10.5%) bolus groups.

The FEAST result was unexpected and so contrary to accepted thinking that it prompted widespread debate, including whether findings in the resource-poor area of the world where the FEAST trial was conducted could be extrapolated to centers elsewhere in the world. Arguing for benefit, fluid resuscitation is known to increase pulse pressure and urinary output. Arguing against benefit, pulmonary edema is a known complication of bolus fluid replacement.

In an attempt to address and potentially resolve this controversy, data collected in the FEAST trial along with four other sets of data involving volume expansion in critically ill children were evaluated with a focus on changes in cardiovascular, neurological, and respiratory function. Analysis of blood biochemistry and blood oxygen transport were also conducted.

The cardiovascular, respiratory, and neurologic functions were scored on the basis of objective measurements, such as heart rate, respiratory rate, and blood pressure. These measures were evaluated prior to fluid administration and at 1 hour, 4 hours, 8 hours, 24 hours, and 48 hours after fluid administration. Odds ratio (OR) of an adverse outcome were evaluated in the context of each 10-unit change in these scores.

Relative to baseline, there was worsening respiratory and neurological function after fluid administration. Although cardiovascular function improved, hemoglobin concentrations were lower in those who received fluid than in those who did not. Fluid resuscitation was also associated with lower bicarbonate and increased base deficit and chloride at 24 hours.

Regression modeling with physiological variables suggests “that the increased mortality in FEAST can be explained by bolus-induced worsening in respiratory and neurological function, hemodilution, and hyperchloremic acidosis,” according to the authors.

Analyses of the four other sets of data, which included children treated for meningococcal sepsis in the United Kingdom, acutely ill with malaria treated in Malawi, and cohorts of children in South Africa and a London hospital for acute illnesses, provided supportive data.

Although this analysis does not address the value of administering buffered solutions in low volumes, the authors concluded that the data from the FEAST trial are generalizable. They challenge the routine use of bolus infusions of saline or albumin in the initial management of shock, which has been guideline recommended. The risks of fluid resuscitation might be particularly high among children who already have compromised respiratory or neurologic function.

SOURCE: Levin M et al. Lancet Respir Med. 2019;7:581-93.

MADRID – Trial results presented at the European Congress of Rheumatology for three anti–interleukin-17 receptor monoclonal antibodies under investigation for the treatment of axial spondyloarthritis (axSpA), including one for ankylosing spondylitis (AS), appear to support further clinical development and regulatory review to potentially join secukinumab (Cosentyx) and ixekizumab (Taltz) as the only IL-17 inhibitors to be licensed for rheumatic diseases.

Both netakimab and brodalumab (Siliq) achieved positive results in separate phase 3 trials for the treatment of axSpA, while new data from a phase 2b trial of bimekizumab was associated with improvement in the quality of life of patients with AS. Brodalumab is already approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis.
 

Netakimab

Ted Bosworth/MDedge News

The multinational, double-blind, phase 3 trial with netakimab, called the ASTERA trial, randomized 228 patients with radiographic axSpA to either 120 mg of the experimental agent or placebo, each administered subcutaneously in weekly doses in the first 2 weeks and then every other week thereafter. The primary endpoint was a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) at week 16.

A larger proportion of patients in the netakimab arm met the primary endpoint, compared with those in the placebo arm (40.4% vs. 2.63%, respectively; P less than .0001), reported Inna Gaydukova, MD, of Mechnikov North-Western State Medical University, St. Petersburg, Russia.

“Most of the secondary efficacy endpoints also showed a significant advantage for netakimab relative to placebo by week 4, and these advantages remained significant for the remainder of the study,” she said.

The one serious adverse event in the study occurred in the placebo arm. Although mild to moderate anemia and neutropenia were associated with treatment, the drug was well tolerated overall.

“We did observe a significant reduction in inflammatory activity in the spine with MRI at week 16,” Dr. Gaydukova added. Functional improvements in the experimental arm relative to the placebo arm were also observed, although Dr. Gaydukova acknowledged that longer trials are needed to show that these benefits are durable.
 

Brodalumab

The results of a multinational, double-blind, phase 3 trial with brodalumab proved similar to those with netakimab. Conducted in Taiwan, Japan, and South Korea, the trial randomized 159 patients to 210 mg of brodalumab or placebo administered subcutaneously. The therapies were administered on the same schedule as in the netakimab trial. The primary outcome was also the same.

At week 16, 43.8% of those on the experimental agent versus 24.1% of those randomized to placebo achieved ASAS40 (P = .018). As in the netakimab study, greater activity with brodalumab than placebo was also seen on several secondary outcomes, such as ASAS20 (67.5% vs. 41.8%).

“In a subgroup analysis, there was an advantage for brodalumab over placebo whether or not patients had prior experience with a TNF [tumor necrosis factor] inhibitor, regardless of baseline hs-CRP [high sensitivity C-reactive protein] level and independent of HLA type,” reported James Cheng-Chung Wei, MD, of Chung Shan Medical University Hospital, Taichung, Taiwan.

There were no significant differences in the types or rates of adverse events, including serious adverse events, in patients assigned to brodalumab relative to placebo. Suicide ideation, which has been associated with some biologics targeting other immunologic mediators, was evaluated but not seen.

“We think brodalumab has the potential to be a new therapeutic option in axSpA,” said Dr. Wei, who reported that studies in AS are also planned.
 

Bimekizumab

Additional 12-week outcome data from the multinational, double-blind, phase 2b BE AGILE trial of bimekizumab in patients with active AS were presented by Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center.

Unlike secukinumab and most of the other anti–IL-17 receptor monoclonal antibodies in development, bimekizumab inhibits IL-17F in addition to IL-17A, according to Dr. van der Heijde. She cited experimental evidence suggesting that inhibition of both forms of IL-17 results in greater anti-inflammatory response.

In the initial and previously reported data from this dose-ranging study of 303 AS patients, all four doses of bimekizumab (16 mg, 64 mg, 160 mg, or 320 mg) were superior to placebo for the primary endpoint of ASAS40. However, greater relative benefit was observed for the three highest doses.

In the new analysis, symptoms were evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). At 12 weeks, 47.5% of patients on the highest dose of bimekizumab versus only 11.9% of patients randomized to placebo achieved a 50% or greater level of improvement on the BASDAI, called BASDAI 50 (P less than .001).

The greater clinical activity of bimekizumab relative to placebo translated into improvement from baseline in Ankylosing Spondylitis Quality of Life scores. Greater reductions in Ankylosing Spondylitis Quality of Life scores relative to placebo, signaling an improved quality of life, were achieved with all doses, but they reached 4.6 points for the highest dose versus only 1.3 for placebo.

When evaluated with Patient Global Assessment of Disease Activity, another tool that reflects perception of disease burden, the score reduction was 3.3 points for the highest dose versus 1.0 points for placebo. Dr. van der Heijde characterized the reductions at the highest doses versus placebo as “significant” although she did not provide P values.

Like the data presented on the other newer anti–IL-17 therapies, bimekizumab was well tolerated with relatively low rates of adverse events, most of which were mild to moderate in severity, according to Dr. van der Heijde.

“The data from the BE AGILE trial supports phase 3 development in AS,” Dr. van der Heijde said. She noted that trials are also being planned in axSpA.

All three presenting authors reported multiple financial relationships with pharmaceutical companies, including, in each case, the pharmaceutical company that sponsored the trial they presented.

SOURCES: Gaydukova I et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193-4, Abstract OP0232. doi: 10.1136/annrheumdis-2019-eular.6633; Wei JC et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):195, Abstract OP0234. doi: 10.1136/annrheumdis-2019-eular.6888; van der Heijde D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193, Abstract OP0231. doi: 10.1136/annrheumdis-2019-eular.6607.

MADRID – Trial results presented at the European Congress of Rheumatology for three anti–interleukin-17 receptor monoclonal antibodies under investigation for the treatment of axial spondyloarthritis (axSpA), including one for ankylosing spondylitis (AS), appear to support further clinical development and regulatory review to potentially join secukinumab (Cosentyx) and ixekizumab (Taltz) as the only IL-17 inhibitors to be licensed for rheumatic diseases.

Both netakimab and brodalumab (Siliq) achieved positive results in separate phase 3 trials for the treatment of axSpA, while new data from a phase 2b trial of bimekizumab was associated with improvement in the quality of life of patients with AS. Brodalumab is already approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis.
 

Netakimab

Ted Bosworth/MDedge News

The multinational, double-blind, phase 3 trial with netakimab, called the ASTERA trial, randomized 228 patients with radiographic axSpA to either 120 mg of the experimental agent or placebo, each administered subcutaneously in weekly doses in the first 2 weeks and then every other week thereafter. The primary endpoint was a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) at week 16.

A larger proportion of patients in the netakimab arm met the primary endpoint, compared with those in the placebo arm (40.4% vs. 2.63%, respectively; P less than .0001), reported Inna Gaydukova, MD, of Mechnikov North-Western State Medical University, St. Petersburg, Russia.

“Most of the secondary efficacy endpoints also showed a significant advantage for netakimab relative to placebo by week 4, and these advantages remained significant for the remainder of the study,” she said.

The one serious adverse event in the study occurred in the placebo arm. Although mild to moderate anemia and neutropenia were associated with treatment, the drug was well tolerated overall.

“We did observe a significant reduction in inflammatory activity in the spine with MRI at week 16,” Dr. Gaydukova added. Functional improvements in the experimental arm relative to the placebo arm were also observed, although Dr. Gaydukova acknowledged that longer trials are needed to show that these benefits are durable.
 

Brodalumab

The results of a multinational, double-blind, phase 3 trial with brodalumab proved similar to those with netakimab. Conducted in Taiwan, Japan, and South Korea, the trial randomized 159 patients to 210 mg of brodalumab or placebo administered subcutaneously. The therapies were administered on the same schedule as in the netakimab trial. The primary outcome was also the same.

At week 16, 43.8% of those on the experimental agent versus 24.1% of those randomized to placebo achieved ASAS40 (P = .018). As in the netakimab study, greater activity with brodalumab than placebo was also seen on several secondary outcomes, such as ASAS20 (67.5% vs. 41.8%).

“In a subgroup analysis, there was an advantage for brodalumab over placebo whether or not patients had prior experience with a TNF [tumor necrosis factor] inhibitor, regardless of baseline hs-CRP [high sensitivity C-reactive protein] level and independent of HLA type,” reported James Cheng-Chung Wei, MD, of Chung Shan Medical University Hospital, Taichung, Taiwan.

There were no significant differences in the types or rates of adverse events, including serious adverse events, in patients assigned to brodalumab relative to placebo. Suicide ideation, which has been associated with some biologics targeting other immunologic mediators, was evaluated but not seen.

“We think brodalumab has the potential to be a new therapeutic option in axSpA,” said Dr. Wei, who reported that studies in AS are also planned.
 

Bimekizumab

Additional 12-week outcome data from the multinational, double-blind, phase 2b BE AGILE trial of bimekizumab in patients with active AS were presented by Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center.

Unlike secukinumab and most of the other anti–IL-17 receptor monoclonal antibodies in development, bimekizumab inhibits IL-17F in addition to IL-17A, according to Dr. van der Heijde. She cited experimental evidence suggesting that inhibition of both forms of IL-17 results in greater anti-inflammatory response.

In the initial and previously reported data from this dose-ranging study of 303 AS patients, all four doses of bimekizumab (16 mg, 64 mg, 160 mg, or 320 mg) were superior to placebo for the primary endpoint of ASAS40. However, greater relative benefit was observed for the three highest doses.

In the new analysis, symptoms were evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). At 12 weeks, 47.5% of patients on the highest dose of bimekizumab versus only 11.9% of patients randomized to placebo achieved a 50% or greater level of improvement on the BASDAI, called BASDAI 50 (P less than .001).

The greater clinical activity of bimekizumab relative to placebo translated into improvement from baseline in Ankylosing Spondylitis Quality of Life scores. Greater reductions in Ankylosing Spondylitis Quality of Life scores relative to placebo, signaling an improved quality of life, were achieved with all doses, but they reached 4.6 points for the highest dose versus only 1.3 for placebo.

When evaluated with Patient Global Assessment of Disease Activity, another tool that reflects perception of disease burden, the score reduction was 3.3 points for the highest dose versus 1.0 points for placebo. Dr. van der Heijde characterized the reductions at the highest doses versus placebo as “significant” although she did not provide P values.

Like the data presented on the other newer anti–IL-17 therapies, bimekizumab was well tolerated with relatively low rates of adverse events, most of which were mild to moderate in severity, according to Dr. van der Heijde.

“The data from the BE AGILE trial supports phase 3 development in AS,” Dr. van der Heijde said. She noted that trials are also being planned in axSpA.

All three presenting authors reported multiple financial relationships with pharmaceutical companies, including, in each case, the pharmaceutical company that sponsored the trial they presented.

SOURCES: Gaydukova I et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193-4, Abstract OP0232. doi: 10.1136/annrheumdis-2019-eular.6633; Wei JC et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):195, Abstract OP0234. doi: 10.1136/annrheumdis-2019-eular.6888; van der Heijde D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193, Abstract OP0231. doi: 10.1136/annrheumdis-2019-eular.6607.

MADRID – Trial results presented at the European Congress of Rheumatology for three anti–interleukin-17 receptor monoclonal antibodies under investigation for the treatment of axial spondyloarthritis (axSpA), including one for ankylosing spondylitis (AS), appear to support further clinical development and regulatory review to potentially join secukinumab (Cosentyx) and ixekizumab (Taltz) as the only IL-17 inhibitors to be licensed for rheumatic diseases.

Both netakimab and brodalumab (Siliq) achieved positive results in separate phase 3 trials for the treatment of axSpA, while new data from a phase 2b trial of bimekizumab was associated with improvement in the quality of life of patients with AS. Brodalumab is already approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis.
 

Netakimab

Ted Bosworth/MDedge News

The multinational, double-blind, phase 3 trial with netakimab, called the ASTERA trial, randomized 228 patients with radiographic axSpA to either 120 mg of the experimental agent or placebo, each administered subcutaneously in weekly doses in the first 2 weeks and then every other week thereafter. The primary endpoint was a 40% improvement in Assessment of SpondyloArthritis International Society response criteria (ASAS40) at week 16.

A larger proportion of patients in the netakimab arm met the primary endpoint, compared with those in the placebo arm (40.4% vs. 2.63%, respectively; P less than .0001), reported Inna Gaydukova, MD, of Mechnikov North-Western State Medical University, St. Petersburg, Russia.

“Most of the secondary efficacy endpoints also showed a significant advantage for netakimab relative to placebo by week 4, and these advantages remained significant for the remainder of the study,” she said.

The one serious adverse event in the study occurred in the placebo arm. Although mild to moderate anemia and neutropenia were associated with treatment, the drug was well tolerated overall.

“We did observe a significant reduction in inflammatory activity in the spine with MRI at week 16,” Dr. Gaydukova added. Functional improvements in the experimental arm relative to the placebo arm were also observed, although Dr. Gaydukova acknowledged that longer trials are needed to show that these benefits are durable.
 

Brodalumab

The results of a multinational, double-blind, phase 3 trial with brodalumab proved similar to those with netakimab. Conducted in Taiwan, Japan, and South Korea, the trial randomized 159 patients to 210 mg of brodalumab or placebo administered subcutaneously. The therapies were administered on the same schedule as in the netakimab trial. The primary outcome was also the same.

At week 16, 43.8% of those on the experimental agent versus 24.1% of those randomized to placebo achieved ASAS40 (P = .018). As in the netakimab study, greater activity with brodalumab than placebo was also seen on several secondary outcomes, such as ASAS20 (67.5% vs. 41.8%).

“In a subgroup analysis, there was an advantage for brodalumab over placebo whether or not patients had prior experience with a TNF [tumor necrosis factor] inhibitor, regardless of baseline hs-CRP [high sensitivity C-reactive protein] level and independent of HLA type,” reported James Cheng-Chung Wei, MD, of Chung Shan Medical University Hospital, Taichung, Taiwan.

There were no significant differences in the types or rates of adverse events, including serious adverse events, in patients assigned to brodalumab relative to placebo. Suicide ideation, which has been associated with some biologics targeting other immunologic mediators, was evaluated but not seen.

“We think brodalumab has the potential to be a new therapeutic option in axSpA,” said Dr. Wei, who reported that studies in AS are also planned.
 

Bimekizumab

Additional 12-week outcome data from the multinational, double-blind, phase 2b BE AGILE trial of bimekizumab in patients with active AS were presented by Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center.

Unlike secukinumab and most of the other anti–IL-17 receptor monoclonal antibodies in development, bimekizumab inhibits IL-17F in addition to IL-17A, according to Dr. van der Heijde. She cited experimental evidence suggesting that inhibition of both forms of IL-17 results in greater anti-inflammatory response.

In the initial and previously reported data from this dose-ranging study of 303 AS patients, all four doses of bimekizumab (16 mg, 64 mg, 160 mg, or 320 mg) were superior to placebo for the primary endpoint of ASAS40. However, greater relative benefit was observed for the three highest doses.

In the new analysis, symptoms were evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). At 12 weeks, 47.5% of patients on the highest dose of bimekizumab versus only 11.9% of patients randomized to placebo achieved a 50% or greater level of improvement on the BASDAI, called BASDAI 50 (P less than .001).

The greater clinical activity of bimekizumab relative to placebo translated into improvement from baseline in Ankylosing Spondylitis Quality of Life scores. Greater reductions in Ankylosing Spondylitis Quality of Life scores relative to placebo, signaling an improved quality of life, were achieved with all doses, but they reached 4.6 points for the highest dose versus only 1.3 for placebo.

When evaluated with Patient Global Assessment of Disease Activity, another tool that reflects perception of disease burden, the score reduction was 3.3 points for the highest dose versus 1.0 points for placebo. Dr. van der Heijde characterized the reductions at the highest doses versus placebo as “significant” although she did not provide P values.

Like the data presented on the other newer anti–IL-17 therapies, bimekizumab was well tolerated with relatively low rates of adverse events, most of which were mild to moderate in severity, according to Dr. van der Heijde.

“The data from the BE AGILE trial supports phase 3 development in AS,” Dr. van der Heijde said. She noted that trials are also being planned in axSpA.

All three presenting authors reported multiple financial relationships with pharmaceutical companies, including, in each case, the pharmaceutical company that sponsored the trial they presented.

SOURCES: Gaydukova I et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193-4, Abstract OP0232. doi: 10.1136/annrheumdis-2019-eular.6633; Wei JC et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):195, Abstract OP0234. doi: 10.1136/annrheumdis-2019-eular.6888; van der Heijde D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):193, Abstract OP0231. doi: 10.1136/annrheumdis-2019-eular.6607.

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.

At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.

“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.

The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).

Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).

However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.

Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
 

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.

MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.

At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.

“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.

The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).

Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).

However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.

Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
 

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.

MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.

At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.

“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.

The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).

Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).

However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.

Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
 

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.

MADRID – Initial results of an ongoing small pilot study of the anti-interferon gamma (IFN-gamma) monoclonal antibody emapalumab has demonstrated efficacy in the treatment of glucocorticoid-refractory macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (SJIA).

Ted Bosworth/MDedge News

“By week 4 there was a complete response in all six patients treated. All of them had failed conventional therapy,” Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology at IRCCS Ospedale Pediatrico Bambino Gesù, Rome, reported at the European Congress of Rheumatology.

The results are the first of a multicenter, pilot study with twin protocols in Europe and North America. Emapalumab (Gamifant) is already approved by the Food and Drug Administration for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) unresponsive to conventional therapy.

The study is enrolling children with MAS complicating SJIA that is unresponsive to high-dose intravenous glucocorticoids. Emapalumab, which has been shown to neutralize IFN-gamma in animal models, is being administered in an initial dose of 6 mg/kg followed by doses of 3 mg/kg every 3 days for 4 weeks.

MAS is a common complication of rheumatic diseases, particularly SJIA, according to Dr. De Benedetti. It has been characterized as a secondary form of HLH involving an excessive activation and expansion of macrophages as well as T cells. It can produce a wide variety of complications, including hepatosplenomegaly, liver dysfunction, and coagulation abnormalities. If uncontrolled, it can lead to organ failure and death.


Among the first six patients, four had confirmed SJIA and two had presumptive SJIA. The average age was 11 years with a range of 2 to 25 years. Four of the patients were female.

Many of the patients had failed therapies in addition to glucocorticoids, such as cyclosporine and anakinra. A diagnosis of HLH and prior treatment with a biologic therapy were exclusion criteria.

By 8 weeks, six had a complete response, which included the resolution of symptoms by normalization of ferritin, liver enzymes, and D-dimers. In three of the six patients, a complete response was achieved by week 4.

“Steroid tapering by investigator discretion was permitted, and four of the six patients had a meaningful tapering of steroids within 8 weeks,” Dr. De Benedetti reported.

Of the three serious adverse events recorded so far, only reactivation of cytomegalovirus (CMV) infection was attributed to emapalumab. This infection resolved with treatment. Several other infections observed over the course of the study were not thought to be related to treatment.

The initial results have encouraged an expansion of the study protocol in Europe where several treatment centers are expected to begin enrolling patients shortly. A second parallel study protocol will begin soon in North America, but no patient had been treated at the time that Dr. De Benedetti presented these initial findings.

Based on evidence that IFN-gamma drives hyperinflammation and hypercytokinemia in MAS, the initial results with emapalumab are encouraging, according to Dr. De Benedetti. He said the results not only provide evidence that emapalumab is active in MAS but support the pathogenic role of IFN-gamma in this disease.

Dr. De Benedetti reported financial relationships with multiple pharmaceutical companies, including SOBI, the sponsor of this study.

SOURCE: De Benedetti F et al. Ann Rheum Dis. Jun 2019;78(Suppl2):178. Abstract OPO204, doi: 10.1136/annrheumdis-2019-eular.3341.

MADRID – Initial results of an ongoing small pilot study of the anti-interferon gamma (IFN-gamma) monoclonal antibody emapalumab has demonstrated efficacy in the treatment of glucocorticoid-refractory macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (SJIA).

Ted Bosworth/MDedge News

“By week 4 there was a complete response in all six patients treated. All of them had failed conventional therapy,” Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology at IRCCS Ospedale Pediatrico Bambino Gesù, Rome, reported at the European Congress of Rheumatology.

The results are the first of a multicenter, pilot study with twin protocols in Europe and North America. Emapalumab (Gamifant) is already approved by the Food and Drug Administration for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) unresponsive to conventional therapy.

The study is enrolling children with MAS complicating SJIA that is unresponsive to high-dose intravenous glucocorticoids. Emapalumab, which has been shown to neutralize IFN-gamma in animal models, is being administered in an initial dose of 6 mg/kg followed by doses of 3 mg/kg every 3 days for 4 weeks.

MAS is a common complication of rheumatic diseases, particularly SJIA, according to Dr. De Benedetti. It has been characterized as a secondary form of HLH involving an excessive activation and expansion of macrophages as well as T cells. It can produce a wide variety of complications, including hepatosplenomegaly, liver dysfunction, and coagulation abnormalities. If uncontrolled, it can lead to organ failure and death.


Among the first six patients, four had confirmed SJIA and two had presumptive SJIA. The average age was 11 years with a range of 2 to 25 years. Four of the patients were female.

Many of the patients had failed therapies in addition to glucocorticoids, such as cyclosporine and anakinra. A diagnosis of HLH and prior treatment with a biologic therapy were exclusion criteria.

By 8 weeks, six had a complete response, which included the resolution of symptoms by normalization of ferritin, liver enzymes, and D-dimers. In three of the six patients, a complete response was achieved by week 4.

“Steroid tapering by investigator discretion was permitted, and four of the six patients had a meaningful tapering of steroids within 8 weeks,” Dr. De Benedetti reported.

Of the three serious adverse events recorded so far, only reactivation of cytomegalovirus (CMV) infection was attributed to emapalumab. This infection resolved with treatment. Several other infections observed over the course of the study were not thought to be related to treatment.

The initial results have encouraged an expansion of the study protocol in Europe where several treatment centers are expected to begin enrolling patients shortly. A second parallel study protocol will begin soon in North America, but no patient had been treated at the time that Dr. De Benedetti presented these initial findings.

Based on evidence that IFN-gamma drives hyperinflammation and hypercytokinemia in MAS, the initial results with emapalumab are encouraging, according to Dr. De Benedetti. He said the results not only provide evidence that emapalumab is active in MAS but support the pathogenic role of IFN-gamma in this disease.

Dr. De Benedetti reported financial relationships with multiple pharmaceutical companies, including SOBI, the sponsor of this study.

SOURCE: De Benedetti F et al. Ann Rheum Dis. Jun 2019;78(Suppl2):178. Abstract OPO204, doi: 10.1136/annrheumdis-2019-eular.3341.

MADRID – Initial results of an ongoing small pilot study of the anti-interferon gamma (IFN-gamma) monoclonal antibody emapalumab has demonstrated efficacy in the treatment of glucocorticoid-refractory macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (SJIA).

Ted Bosworth/MDedge News

“By week 4 there was a complete response in all six patients treated. All of them had failed conventional therapy,” Fabrizio De Benedetti, MD, PhD, head of the division of rheumatology at IRCCS Ospedale Pediatrico Bambino Gesù, Rome, reported at the European Congress of Rheumatology.

The results are the first of a multicenter, pilot study with twin protocols in Europe and North America. Emapalumab (Gamifant) is already approved by the Food and Drug Administration for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) unresponsive to conventional therapy.

The study is enrolling children with MAS complicating SJIA that is unresponsive to high-dose intravenous glucocorticoids. Emapalumab, which has been shown to neutralize IFN-gamma in animal models, is being administered in an initial dose of 6 mg/kg followed by doses of 3 mg/kg every 3 days for 4 weeks.

MAS is a common complication of rheumatic diseases, particularly SJIA, according to Dr. De Benedetti. It has been characterized as a secondary form of HLH involving an excessive activation and expansion of macrophages as well as T cells. It can produce a wide variety of complications, including hepatosplenomegaly, liver dysfunction, and coagulation abnormalities. If uncontrolled, it can lead to organ failure and death.


Among the first six patients, four had confirmed SJIA and two had presumptive SJIA. The average age was 11 years with a range of 2 to 25 years. Four of the patients were female.

Many of the patients had failed therapies in addition to glucocorticoids, such as cyclosporine and anakinra. A diagnosis of HLH and prior treatment with a biologic therapy were exclusion criteria.

By 8 weeks, six had a complete response, which included the resolution of symptoms by normalization of ferritin, liver enzymes, and D-dimers. In three of the six patients, a complete response was achieved by week 4.

“Steroid tapering by investigator discretion was permitted, and four of the six patients had a meaningful tapering of steroids within 8 weeks,” Dr. De Benedetti reported.

Of the three serious adverse events recorded so far, only reactivation of cytomegalovirus (CMV) infection was attributed to emapalumab. This infection resolved with treatment. Several other infections observed over the course of the study were not thought to be related to treatment.

The initial results have encouraged an expansion of the study protocol in Europe where several treatment centers are expected to begin enrolling patients shortly. A second parallel study protocol will begin soon in North America, but no patient had been treated at the time that Dr. De Benedetti presented these initial findings.

Based on evidence that IFN-gamma drives hyperinflammation and hypercytokinemia in MAS, the initial results with emapalumab are encouraging, according to Dr. De Benedetti. He said the results not only provide evidence that emapalumab is active in MAS but support the pathogenic role of IFN-gamma in this disease.

Dr. De Benedetti reported financial relationships with multiple pharmaceutical companies, including SOBI, the sponsor of this study.

SOURCE: De Benedetti F et al. Ann Rheum Dis. Jun 2019;78(Suppl2):178. Abstract OPO204, doi: 10.1136/annrheumdis-2019-eular.3341.

MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).

Mitchel L. Zoler/MDedge News

One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.

“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).

Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.

Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.

“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.

In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.

At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m², and 30.4% were obese as defined by a BMI greater than 30 kg/m². The mean baseline BMI was 28.1 kg/m². The mean age of the study population was 49.7 years. Slightly more than half were female.

Relative to a BMI of 30 kg/m² or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).

“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”

The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m², and the actual average BMI was 35 kg/m². The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.

Mitchel L. Zoler/MDedge News

Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.

“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”

An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.

“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.

Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.

Mitchel L. Zoler contributed to this report.

SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.

MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).

Mitchel L. Zoler/MDedge News

One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.

“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).

Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.

Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.

“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.

In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.

At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m², and 30.4% were obese as defined by a BMI greater than 30 kg/m². The mean baseline BMI was 28.1 kg/m². The mean age of the study population was 49.7 years. Slightly more than half were female.

Relative to a BMI of 30 kg/m² or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).

“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”

The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m², and the actual average BMI was 35 kg/m². The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.

Mitchel L. Zoler/MDedge News

Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.

“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”

An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.

“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.

Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.

Mitchel L. Zoler contributed to this report.

SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.

MADRID – Two sets of data presented at the European Congress of Rheumatology support the potential for weight loss to be a valuable adjunctive strategy for improving outcomes in patients with psoriatic arthritis (PsA).

Mitchel L. Zoler/MDedge News

One set, drawn from the ongoing PsABio observational study, correlated increasing body mass index with greater disease activity and greater disability. Another, based on patients followed for 12 months, showed that a weight loss of about 15% is associated with a significant reduction in PsA activity.

“As clinicians, we largely focus on drugs in the treatment of PsA, but these data draw attention to obesity as a potential target for improving outcomes in PsA,” said Stefan Siebert, MD, a rheumatologist at the Institute of Infection, Immunity, and Inflammation at the University of Glasgow (Scotland).

Dr. Siebert cautioned that his data show association, not causation, but he said these data add to a growing body of evidence that provide compelling support for trials to test the premise that weight loss improves outcomes.

Although not a trial, a study by Eva Klingberg, MD, PhD, of the Sahlgrenska Academy at the University of Gothenburg (Sweden) and her associates tested this premise and showed weight loss was associated with improvement in multiple PsA activity parameters 6 and 12 months after a significant weight loss program.

“This is just one study, so we need more data, but we are already using weight loss to manage PsA in obese patients in Sweden,” said Dr. Klingberg, speaking about her work in advance of the presentation. Like Dr. Siebert, she agreed that weight loss is an important potential treatment strategy in PsA.

In the observational PsABio study, which is following patients with PsA at rheumatology centers in eight European countries, the goal of its analysis was to evaluate disease activity and outcomes in relationship to baseline weight for patients starting a biologic therapy as part of standard clinical practice. Of the 917 patients evaluated, 450 started ustekinumab (Stelara) and 467 started a tumor necrosis factor inhibitor (TNFi). The researchers had weight data for 827 of these patients.

At the time of enrollment, 40% were overweight as defined by a body mass index (BMI) ranging from 25 to 29 kg/m², and 30.4% were obese as defined by a BMI greater than 30 kg/m². The mean baseline BMI was 28.1 kg/m². The mean age of the study population was 49.7 years. Slightly more than half were female.

Relative to a BMI of 30 kg/m² or less, higher BMI at baseline is shown in multiple regression analysis to be independently and significantly linked to disease activity assessed by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA; P = .026), to patient perception of disease impact as measured by Psoriatic Arthritis Impact of Disease (PsAID-12; P less than .0001), and to greater disability as measured with Health Assessment Questionnaire Disability Index (HAQ-DI; P less than .0001).

“There are multiple sets of data that show obesity predicts who develops PsA. Our data further show that, of patients with PsA who are candidates for a biologic, those with obesity have greater disease activity,” Dr. Siebert said. “We are using all of these expensive drugs, but I think there is now a need to also focus on lifestyle interventions, in addition to drug therapy, to reduce disease activity and improve outcomes in PsA.”

The data to be presented by Dr. Klingberg provide a step in that direction. In this study, 46 PsA patients participated in a weight-loss treatment that restricted calorie intake to 640 kcal/day, and the researchers followed 39 of these patients for 1 year. The participants averaged 56 years old, and almost two-thirds were women. All enrolled patients had to have a BMI of at least 33 kg/m², and the actual average BMI was 35 kg/m². The median weight loss among the 39 patients followed for 1 year after the start of a 12- to 16-week weight-loss treatment was 16.1 kg, representing about 16% of their body weight at entry.

Mitchel L. Zoler/MDedge News

Dr. Klingberg showed that disease activity in those who achieved and maintained weight loss after the program was significant at 6 and 12 months when measured with the Psoriatic Arthritis Response Criteria (PsARC) or the American College of Rheumatology (ACR) 20, 50, and 70 criteria. In the 39 patients followed for 12 months, 36% fulfilled PsARC, and 54%, 36%, and 15% fulfilled the ACR 20, 50, and 70 responses, respectively.

“In Sweden, any obese individual can be referred for a weight loss program because of the multiple health benefits that are associated with weight reduction,” Dr. Klingberg explained. “We were able to look at patients with PsA and show that this substantially reduces the burden of their joint disease in addition to the other health advantages of losing weight.”

An improvement in symptoms is a logical expectation from reducing the mechanical strain imposed by obesity on inflamed joints, but Dr. Klingberg is more impressed by the potential for weight loss to reduce the proinflammatory signaling generated by adipose tissue. In PsA, there is evidence that weight loss reduces disease activity in the skin, as well as the joints, which supports this link.

“We need more data to document the benefits from weight loss in patients with PsA, but I think management of the comorbidities of PsA, including obesity, is something that should already be routinely discussed with patients,” Dr. Klingberg said.

Dr. Siebert has been a consultant to or speaker on behalf of AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, and UCB, and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB. Dr. Klingberg has been an advisor to Novartis, a speaker on behalf of Lilly, and has receive research funding from Roche.

Mitchel L. Zoler contributed to this report.

SOURCE: Siebert S et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69. Abstract OP0007. doi: 10.1136/annrheumdis-2019-eular.5841; Klingberg E et al. Ann Rheum Dis. Jun 2019;78(suppl 2):69-70. Abstract OP0008. doi: 10.1136/annrheumdis-2019-eular.5551.

MADRID – The addition of leflunomide to standard glucocorticoids (GCs) in the treatment of IgG4-related disease increases the median duration of response, reduces the proportion of patients with relapse within 12 months, and permits GCs to be tapered, according to results of a randomized trial presented at the European Congress of Rheumatology.

“The rate of adverse events with the addition of leflunomide was numerically higher, but there were no significant differences in risks of any specific adverse event,” reported Feng Huang, MD, of the department of rheumatology at Chinese People’s Liberation Army General Hospital in Beijing.

GCs are highly effective in IgG4-related disease, which is an autoimmune process driven by elevated concentrations of the antibody IgG4 in the tissue of affected organs and in the serum. It has been described in a broad array of sites, including the heart, lung, kidneys, and meninges. It has been widely recognized only in the last 10 years, according to Dr. Huang. Although most patients respond to GCs, he said the problem is that about 50% of patients relapse within 12 months and more than 90% within 3 years.

This randomized, controlled study was conducted after positive results were observed with leflunomide in a small, uncontrolled pilot study published several years ago (Intern Med J. 2017 Jun;47[6]:680-9. doi: 10.1111/imj.13430). In this randomized trial, the objectives were to confirm that leflunomide extends the relapse-free period and has acceptable safety relative to GC alone.

Patients with confirmed IgG4-related disease were enrolled. Patients randomized to GC were started on 0.5 to 0.8 mg/kg per day. A predefined taper regimen was employed in those with symptom control. Those randomized to the experimental arm received GC in the same dose and schedule plus 20 mg/day of leflunomide.

The 33 patients in each group were well matched at baseline for age, comorbidities, and disease severity.

At the end of 12 months, 50% of those treated with GC alone versus 21.2% of those treated with GC plus leflunomide had relapse. That translated into a significantly higher hazard ratio (HR) for relapse in the GC monotherapy group (HR, 1.75; P = .034).

The mean duration of remission was 7 months on the combination versus 3 months on GC alone. Dr. Huang also reported a significantly higher proportion of complete responses in the group receiving the combination.

In addition, “more patients on the combination therapy were able to adhere to the steroid-tapering schedule without relapse,” Dr. Huang reported. The rate of 54.5% of patients on combination therapy who were able to reach a daily GC dose of 5 mg/day or less proved significantly higher than the 18.2% rate seen with GC alone (P = .002).


Adverse events were reported by 54% of those on the combination versus 42% of those on monotherapy, but this difference did not reach statistical significance. The biggest differences in adverse events were the proportions of patients with infections (18.2% vs. 12.1%) and elevated liver enzymes (12.1% vs. 3.0%), both of which were more common in the combination therapy group. Neither of these differences was statistically significant.

Of patients with relapses, the most common organs involved were the salivary gland, the pancreas, and the bile ducts, each accounting for relapse in five patients. Other organs in which relapse occurred included the lacrimal gland and the skin. There were three cases of relapse characterized by retroperitoneal fibrosis.

Over the course of follow-up, new-onset diabetes mellitus occurred in 21.2% and 27.3% of the combination and GC-only groups, respectively. This difference also did not reach statistical significance.

Although this study was small with an open-label design, Dr. Huang said the data strongly suggest that a combination of leflunomide and GC is superior to GC alone. Based on these results, he said a starting dose of 20 mg/day of leflunomide is a reasonable standard in this setting.

Dr. Huang and colleagues reported no potential conflicts of interest.

SOURCE: Wang Y et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):157. Abstract OPO164, doi: 10.1136/annrheumdis-2019-eular.5717

MADRID – The addition of leflunomide to standard glucocorticoids (GCs) in the treatment of IgG4-related disease increases the median duration of response, reduces the proportion of patients with relapse within 12 months, and permits GCs to be tapered, according to results of a randomized trial presented at the European Congress of Rheumatology.

“The rate of adverse events with the addition of leflunomide was numerically higher, but there were no significant differences in risks of any specific adverse event,” reported Feng Huang, MD, of the department of rheumatology at Chinese People’s Liberation Army General Hospital in Beijing.

GCs are highly effective in IgG4-related disease, which is an autoimmune process driven by elevated concentrations of the antibody IgG4 in the tissue of affected organs and in the serum. It has been described in a broad array of sites, including the heart, lung, kidneys, and meninges. It has been widely recognized only in the last 10 years, according to Dr. Huang. Although most patients respond to GCs, he said the problem is that about 50% of patients relapse within 12 months and more than 90% within 3 years.

This randomized, controlled study was conducted after positive results were observed with leflunomide in a small, uncontrolled pilot study published several years ago (Intern Med J. 2017 Jun;47[6]:680-9. doi: 10.1111/imj.13430). In this randomized trial, the objectives were to confirm that leflunomide extends the relapse-free period and has acceptable safety relative to GC alone.

Patients with confirmed IgG4-related disease were enrolled. Patients randomized to GC were started on 0.5 to 0.8 mg/kg per day. A predefined taper regimen was employed in those with symptom control. Those randomized to the experimental arm received GC in the same dose and schedule plus 20 mg/day of leflunomide.

The 33 patients in each group were well matched at baseline for age, comorbidities, and disease severity.

At the end of 12 months, 50% of those treated with GC alone versus 21.2% of those treated with GC plus leflunomide had relapse. That translated into a significantly higher hazard ratio (HR) for relapse in the GC monotherapy group (HR, 1.75; P = .034).

The mean duration of remission was 7 months on the combination versus 3 months on GC alone. Dr. Huang also reported a significantly higher proportion of complete responses in the group receiving the combination.

In addition, “more patients on the combination therapy were able to adhere to the steroid-tapering schedule without relapse,” Dr. Huang reported. The rate of 54.5% of patients on combination therapy who were able to reach a daily GC dose of 5 mg/day or less proved significantly higher than the 18.2% rate seen with GC alone (P = .002).


Adverse events were reported by 54% of those on the combination versus 42% of those on monotherapy, but this difference did not reach statistical significance. The biggest differences in adverse events were the proportions of patients with infections (18.2% vs. 12.1%) and elevated liver enzymes (12.1% vs. 3.0%), both of which were more common in the combination therapy group. Neither of these differences was statistically significant.

Of patients with relapses, the most common organs involved were the salivary gland, the pancreas, and the bile ducts, each accounting for relapse in five patients. Other organs in which relapse occurred included the lacrimal gland and the skin. There were three cases of relapse characterized by retroperitoneal fibrosis.

Over the course of follow-up, new-onset diabetes mellitus occurred in 21.2% and 27.3% of the combination and GC-only groups, respectively. This difference also did not reach statistical significance.

Although this study was small with an open-label design, Dr. Huang said the data strongly suggest that a combination of leflunomide and GC is superior to GC alone. Based on these results, he said a starting dose of 20 mg/day of leflunomide is a reasonable standard in this setting.

Dr. Huang and colleagues reported no potential conflicts of interest.

SOURCE: Wang Y et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):157. Abstract OPO164, doi: 10.1136/annrheumdis-2019-eular.5717

MADRID – The addition of leflunomide to standard glucocorticoids (GCs) in the treatment of IgG4-related disease increases the median duration of response, reduces the proportion of patients with relapse within 12 months, and permits GCs to be tapered, according to results of a randomized trial presented at the European Congress of Rheumatology.

“The rate of adverse events with the addition of leflunomide was numerically higher, but there were no significant differences in risks of any specific adverse event,” reported Feng Huang, MD, of the department of rheumatology at Chinese People’s Liberation Army General Hospital in Beijing.

GCs are highly effective in IgG4-related disease, which is an autoimmune process driven by elevated concentrations of the antibody IgG4 in the tissue of affected organs and in the serum. It has been described in a broad array of sites, including the heart, lung, kidneys, and meninges. It has been widely recognized only in the last 10 years, according to Dr. Huang. Although most patients respond to GCs, he said the problem is that about 50% of patients relapse within 12 months and more than 90% within 3 years.

This randomized, controlled study was conducted after positive results were observed with leflunomide in a small, uncontrolled pilot study published several years ago (Intern Med J. 2017 Jun;47[6]:680-9. doi: 10.1111/imj.13430). In this randomized trial, the objectives were to confirm that leflunomide extends the relapse-free period and has acceptable safety relative to GC alone.

Patients with confirmed IgG4-related disease were enrolled. Patients randomized to GC were started on 0.5 to 0.8 mg/kg per day. A predefined taper regimen was employed in those with symptom control. Those randomized to the experimental arm received GC in the same dose and schedule plus 20 mg/day of leflunomide.

The 33 patients in each group were well matched at baseline for age, comorbidities, and disease severity.

At the end of 12 months, 50% of those treated with GC alone versus 21.2% of those treated with GC plus leflunomide had relapse. That translated into a significantly higher hazard ratio (HR) for relapse in the GC monotherapy group (HR, 1.75; P = .034).

The mean duration of remission was 7 months on the combination versus 3 months on GC alone. Dr. Huang also reported a significantly higher proportion of complete responses in the group receiving the combination.

In addition, “more patients on the combination therapy were able to adhere to the steroid-tapering schedule without relapse,” Dr. Huang reported. The rate of 54.5% of patients on combination therapy who were able to reach a daily GC dose of 5 mg/day or less proved significantly higher than the 18.2% rate seen with GC alone (P = .002).


Adverse events were reported by 54% of those on the combination versus 42% of those on monotherapy, but this difference did not reach statistical significance. The biggest differences in adverse events were the proportions of patients with infections (18.2% vs. 12.1%) and elevated liver enzymes (12.1% vs. 3.0%), both of which were more common in the combination therapy group. Neither of these differences was statistically significant.

Of patients with relapses, the most common organs involved were the salivary gland, the pancreas, and the bile ducts, each accounting for relapse in five patients. Other organs in which relapse occurred included the lacrimal gland and the skin. There were three cases of relapse characterized by retroperitoneal fibrosis.

Over the course of follow-up, new-onset diabetes mellitus occurred in 21.2% and 27.3% of the combination and GC-only groups, respectively. This difference also did not reach statistical significance.

Although this study was small with an open-label design, Dr. Huang said the data strongly suggest that a combination of leflunomide and GC is superior to GC alone. Based on these results, he said a starting dose of 20 mg/day of leflunomide is a reasonable standard in this setting.

Dr. Huang and colleagues reported no potential conflicts of interest.

SOURCE: Wang Y et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):157. Abstract OPO164, doi: 10.1136/annrheumdis-2019-eular.5717

MADRID – Evidence for always using imaging in an adjunctive role to clinical findings in the diagnosis and assessment of axial spondyloarthritis (axSpA) continues to grow, two experts agreed in a scientific session at the European Congress of Rheumatology.

“Imaging has to be understood in the context of other findings. With the patient history, the physical examination, and the laboratory results, the value of imaging improves substantially. Therefore, before an image is ordered it is important to ask how likely is it that a patient has axial spondylitis,” said Floris A. van Gaalen, MD, PhD, of Leiden (Netherlands) University Medical Center.

As one of the experts who participated in the scientific session, Dr. van Gaalen focused specifically on the value of x-ray and MRI in the diagnosis of axSpA, emphasizing their limited value if interpreted without clinical context. He explained that even highly experienced radiologists are fooled, particularly at early stages of disease.


Although the quality of imaging has been increasing steadily, “there is no cookbook approach with which you can guarantee a diagnosis of spondyloarthritis. Imaging can be valuable, but there is a risk of false positives because features on imaging, such as bone marrow edema, are shared with other sources of back pain,” Dr. van Gaalen said.

Considering the importance of context, Dr. van Gaalen advised clinicians against reading the radiology report without evaluating the images themselves. He said the features on imaging make more sense when they are considered at the same time as the patient’s history, symptoms, and laboratory reports.

Order imaging relevant to treatment decisions

Assigned to discuss the value of imaging for assessing progression, Xenofon Baraliakos, MD, a rheumatologist and clinical researcher at Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany, offered the same message.

Ted Bosworth/MDedge News

“It is important to consider all of the clinical information available, not just the features on imaging,” Dr. Baraliakos said. Often, MRI findings provide corroboration for other objective measures of disease status, but Dr. Baraliakos advised that imaging should be ordered only when it has the potential to alter therapy.

“What we can learn from imaging might be interesting, but the question to ask is whether it is useful,” Dr. Baraliakos said. Rather than incurring the costs of imaging for reassurance, Dr. Baraliakos recommended ordering these studies with specific objectives relevant to treatment decisions.

Neither Dr. van Gaalen nor Dr. Baraliakos denied the value of imaging, particularly MRI, to increase confidence in the diagnosis of axSpA or to guide therapy. Rather, their point was that imaging should not be considered a reliable stand-alone axSpA assessment strategy.
 

Clinical and imaging findings better then imaging alone

Data from a blinded radiology study presented during the same scientific session reinforced this conclusion. Led by Dr. Baraliakos and presented separately from his discussion about the adjunctive nature of imaging data in axSpA, the study showed that rheumatologists with access to both clinical and imaging data can detect a greater proportion of axSpA than radiologists working from imaging data alone.

In this study, 300 consecutive patients suspected of axSpA were enrolled. All had chronic back pain of more than 3 months’ duration. While highly experienced radiologists were asked to diagnose or rule out a diagnosis of axSpA on the basis of the MRI blinded to other clinical information, experienced rheumatologists evaluated the patients with access to all clinical, laboratory, and imaging data.

A diagnosis of axSpA was reached in 131 patients by the rheumatologists. The remaining 169 were determined not to have axSpA. Although the radiologists agreed on those with or without axSpA in 86.3% of cases, there were 31 cases (28.1%) in which rheumatologists diagnosed axSpA but radiologists did not.

In an analysis of which MRI features were considered critical by radiologists when there was agreement, they identified bone marrow edema in seven cases (7.2%). In 30 cases (30.9%), the radiologists considered the presence of chronic lesions to be critical to their diagnosis. In the remaining 69.9% of cases, radiologists were confident in their diagnosis only when both bone edema and chronic lesions were present.

Not surprisingly, the presence of chronic lesions and more pronounced bone marrow edema permitted both radiologists and rheumatologists to increase their confidence when discriminating between axSpA and non-axSpA patients.

“The combination of structural changes and bone marrow edema as assessed by MRI performed best in the process of diagnosing or ruling out axSpA in this real-life setting at our center,” Dr. Baraliakos said.

However, when only one or two features are considered, trade-offs of lower sensitivity for higher specificity or higher sensitivity for lower specificity occur. For example, although the specificity for a diagnosis of axSpA reached 99.4% when both bone marrow edema and ankylosis are present, the sensitivity of this finding was only 5.3%, according to data provided by Dr. Baraliakos. Conversely, the presence of sclerosis had a sensitivity of 81.7% but a specificity of only 43.2%.

One lesson from this analysis is that there is “increasing insecurity of only including bone marrow edema of the sacroiliac joint as the major criterion for diagnosing axSpA,” Dr. Baraliakos said. However, the larger point in the context of the earlier expert comments is that MRI findings should be considered important but insufficient for the evaluation of axSpA.

SOURCE: Baraliakos X et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):255-6. Abstract OPO344, doi: 10.1136/annrheumdis-2019-eular.5027

MADRID – Evidence for always using imaging in an adjunctive role to clinical findings in the diagnosis and assessment of axial spondyloarthritis (axSpA) continues to grow, two experts agreed in a scientific session at the European Congress of Rheumatology.

“Imaging has to be understood in the context of other findings. With the patient history, the physical examination, and the laboratory results, the value of imaging improves substantially. Therefore, before an image is ordered it is important to ask how likely is it that a patient has axial spondylitis,” said Floris A. van Gaalen, MD, PhD, of Leiden (Netherlands) University Medical Center.

As one of the experts who participated in the scientific session, Dr. van Gaalen focused specifically on the value of x-ray and MRI in the diagnosis of axSpA, emphasizing their limited value if interpreted without clinical context. He explained that even highly experienced radiologists are fooled, particularly at early stages of disease.


Although the quality of imaging has been increasing steadily, “there is no cookbook approach with which you can guarantee a diagnosis of spondyloarthritis. Imaging can be valuable, but there is a risk of false positives because features on imaging, such as bone marrow edema, are shared with other sources of back pain,” Dr. van Gaalen said.

Considering the importance of context, Dr. van Gaalen advised clinicians against reading the radiology report without evaluating the images themselves. He said the features on imaging make more sense when they are considered at the same time as the patient’s history, symptoms, and laboratory reports.

Order imaging relevant to treatment decisions

Assigned to discuss the value of imaging for assessing progression, Xenofon Baraliakos, MD, a rheumatologist and clinical researcher at Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany, offered the same message.

Ted Bosworth/MDedge News

“It is important to consider all of the clinical information available, not just the features on imaging,” Dr. Baraliakos said. Often, MRI findings provide corroboration for other objective measures of disease status, but Dr. Baraliakos advised that imaging should be ordered only when it has the potential to alter therapy.

“What we can learn from imaging might be interesting, but the question to ask is whether it is useful,” Dr. Baraliakos said. Rather than incurring the costs of imaging for reassurance, Dr. Baraliakos recommended ordering these studies with specific objectives relevant to treatment decisions.

Neither Dr. van Gaalen nor Dr. Baraliakos denied the value of imaging, particularly MRI, to increase confidence in the diagnosis of axSpA or to guide therapy. Rather, their point was that imaging should not be considered a reliable stand-alone axSpA assessment strategy.
 

Clinical and imaging findings better then imaging alone

Data from a blinded radiology study presented during the same scientific session reinforced this conclusion. Led by Dr. Baraliakos and presented separately from his discussion about the adjunctive nature of imaging data in axSpA, the study showed that rheumatologists with access to both clinical and imaging data can detect a greater proportion of axSpA than radiologists working from imaging data alone.

In this study, 300 consecutive patients suspected of axSpA were enrolled. All had chronic back pain of more than 3 months’ duration. While highly experienced radiologists were asked to diagnose or rule out a diagnosis of axSpA on the basis of the MRI blinded to other clinical information, experienced rheumatologists evaluated the patients with access to all clinical, laboratory, and imaging data.

A diagnosis of axSpA was reached in 131 patients by the rheumatologists. The remaining 169 were determined not to have axSpA. Although the radiologists agreed on those with or without axSpA in 86.3% of cases, there were 31 cases (28.1%) in which rheumatologists diagnosed axSpA but radiologists did not.

In an analysis of which MRI features were considered critical by radiologists when there was agreement, they identified bone marrow edema in seven cases (7.2%). In 30 cases (30.9%), the radiologists considered the presence of chronic lesions to be critical to their diagnosis. In the remaining 69.9% of cases, radiologists were confident in their diagnosis only when both bone edema and chronic lesions were present.

Not surprisingly, the presence of chronic lesions and more pronounced bone marrow edema permitted both radiologists and rheumatologists to increase their confidence when discriminating between axSpA and non-axSpA patients.

“The combination of structural changes and bone marrow edema as assessed by MRI performed best in the process of diagnosing or ruling out axSpA in this real-life setting at our center,” Dr. Baraliakos said.

However, when only one or two features are considered, trade-offs of lower sensitivity for higher specificity or higher sensitivity for lower specificity occur. For example, although the specificity for a diagnosis of axSpA reached 99.4% when both bone marrow edema and ankylosis are present, the sensitivity of this finding was only 5.3%, according to data provided by Dr. Baraliakos. Conversely, the presence of sclerosis had a sensitivity of 81.7% but a specificity of only 43.2%.

One lesson from this analysis is that there is “increasing insecurity of only including bone marrow edema of the sacroiliac joint as the major criterion for diagnosing axSpA,” Dr. Baraliakos said. However, the larger point in the context of the earlier expert comments is that MRI findings should be considered important but insufficient for the evaluation of axSpA.

SOURCE: Baraliakos X et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):255-6. Abstract OPO344, doi: 10.1136/annrheumdis-2019-eular.5027

MADRID – Evidence for always using imaging in an adjunctive role to clinical findings in the diagnosis and assessment of axial spondyloarthritis (axSpA) continues to grow, two experts agreed in a scientific session at the European Congress of Rheumatology.

“Imaging has to be understood in the context of other findings. With the patient history, the physical examination, and the laboratory results, the value of imaging improves substantially. Therefore, before an image is ordered it is important to ask how likely is it that a patient has axial spondylitis,” said Floris A. van Gaalen, MD, PhD, of Leiden (Netherlands) University Medical Center.

As one of the experts who participated in the scientific session, Dr. van Gaalen focused specifically on the value of x-ray and MRI in the diagnosis of axSpA, emphasizing their limited value if interpreted without clinical context. He explained that even highly experienced radiologists are fooled, particularly at early stages of disease.


Although the quality of imaging has been increasing steadily, “there is no cookbook approach with which you can guarantee a diagnosis of spondyloarthritis. Imaging can be valuable, but there is a risk of false positives because features on imaging, such as bone marrow edema, are shared with other sources of back pain,” Dr. van Gaalen said.

Considering the importance of context, Dr. van Gaalen advised clinicians against reading the radiology report without evaluating the images themselves. He said the features on imaging make more sense when they are considered at the same time as the patient’s history, symptoms, and laboratory reports.

Order imaging relevant to treatment decisions

Assigned to discuss the value of imaging for assessing progression, Xenofon Baraliakos, MD, a rheumatologist and clinical researcher at Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany, offered the same message.

Ted Bosworth/MDedge News

“It is important to consider all of the clinical information available, not just the features on imaging,” Dr. Baraliakos said. Often, MRI findings provide corroboration for other objective measures of disease status, but Dr. Baraliakos advised that imaging should be ordered only when it has the potential to alter therapy.

“What we can learn from imaging might be interesting, but the question to ask is whether it is useful,” Dr. Baraliakos said. Rather than incurring the costs of imaging for reassurance, Dr. Baraliakos recommended ordering these studies with specific objectives relevant to treatment decisions.

Neither Dr. van Gaalen nor Dr. Baraliakos denied the value of imaging, particularly MRI, to increase confidence in the diagnosis of axSpA or to guide therapy. Rather, their point was that imaging should not be considered a reliable stand-alone axSpA assessment strategy.
 

Clinical and imaging findings better then imaging alone

Data from a blinded radiology study presented during the same scientific session reinforced this conclusion. Led by Dr. Baraliakos and presented separately from his discussion about the adjunctive nature of imaging data in axSpA, the study showed that rheumatologists with access to both clinical and imaging data can detect a greater proportion of axSpA than radiologists working from imaging data alone.

In this study, 300 consecutive patients suspected of axSpA were enrolled. All had chronic back pain of more than 3 months’ duration. While highly experienced radiologists were asked to diagnose or rule out a diagnosis of axSpA on the basis of the MRI blinded to other clinical information, experienced rheumatologists evaluated the patients with access to all clinical, laboratory, and imaging data.

A diagnosis of axSpA was reached in 131 patients by the rheumatologists. The remaining 169 were determined not to have axSpA. Although the radiologists agreed on those with or without axSpA in 86.3% of cases, there were 31 cases (28.1%) in which rheumatologists diagnosed axSpA but radiologists did not.

In an analysis of which MRI features were considered critical by radiologists when there was agreement, they identified bone marrow edema in seven cases (7.2%). In 30 cases (30.9%), the radiologists considered the presence of chronic lesions to be critical to their diagnosis. In the remaining 69.9% of cases, radiologists were confident in their diagnosis only when both bone edema and chronic lesions were present.

Not surprisingly, the presence of chronic lesions and more pronounced bone marrow edema permitted both radiologists and rheumatologists to increase their confidence when discriminating between axSpA and non-axSpA patients.

“The combination of structural changes and bone marrow edema as assessed by MRI performed best in the process of diagnosing or ruling out axSpA in this real-life setting at our center,” Dr. Baraliakos said.

However, when only one or two features are considered, trade-offs of lower sensitivity for higher specificity or higher sensitivity for lower specificity occur. For example, although the specificity for a diagnosis of axSpA reached 99.4% when both bone marrow edema and ankylosis are present, the sensitivity of this finding was only 5.3%, according to data provided by Dr. Baraliakos. Conversely, the presence of sclerosis had a sensitivity of 81.7% but a specificity of only 43.2%.

One lesson from this analysis is that there is “increasing insecurity of only including bone marrow edema of the sacroiliac joint as the major criterion for diagnosing axSpA,” Dr. Baraliakos said. However, the larger point in the context of the earlier expert comments is that MRI findings should be considered important but insufficient for the evaluation of axSpA.

SOURCE: Baraliakos X et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):255-6. Abstract OPO344, doi: 10.1136/annrheumdis-2019-eular.5027