Ted Bosworth

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

MADRID – The musculoskeletal complications of checkpoint inhibitors therapy are sometimes described as RA like, but a detailed analysis of a consecutive series of patients presented at the European Congress of Rheumatology produced the conclusion that the phenotypic expression is unique.

“These manifestations do not necessarily include synovial involvement, so their description as a rheumatoid arthritis–like presentation is not accurate. Rather, our findings suggest the pathology is something completely different and completely new,” said Alexandra Filippopoulou, MD, a rheumatology resident at the University of Patras (Greece).

This comment was based on a prospective study evaluating musculoskeletal complications in patients treated with checkpoint inhibitors over a recent 2-year period. Of the 130 consecutive patients who received a checkpoint inhibitor in the study period, 10 (7.7%) complained of joint pain and were determined to have an inflammatory complication.

The median time to development of musculoskeletal symptoms in this mostly male patient series was 2.5 months. The site of cancer was lung in four, bladder in three, kidney in two, and skin in one. Nivolumab (Opdivo) was the most common checkpoint inhibitor used, but others were represented.

MRI studies were conducted in 8 of the 10 patients. Overall, the MRI studies showed more myofascial than synovial involvement, but Dr. Filippopoulou described three distinct patterns.

In four patients, there was prominent periarticular involvement marked by diffuse swelling in the hands, feet, knees, or a combination of these joints. Synovitis, when observed, was mild, but myositis and fasciitis were common in adjacent tissues.

In three patients with a chief complaint of knee pain, myofasciitis was prominent in the surrounding muscles. Again, synovitis, when observed, was mild. It was unclear whether a partial tear of the quadriceps tendon observed in one patient was checkpoint inhibitor related.

In a third pattern, shared by three other patients, synovitis was prominent, but so was myositis in adjacent muscles. In two of these patients, the inflammatory activity was confined to the hands; in the third, both the knees and the ankle were also involved.


Regardless of these patterns of inflammation, “almost all of these patients continued to show good range of motion, which is not something that is commonly seen in patients with rheumatoid arthritis,” Dr. Filippopoulou observed.

Overall, the joint pain tended to be mild to moderate. They all responded well to low-dose glucocorticoids or analgesics without need to discontinue the anticancer therapy, Dr. Filippopoulou reported.

Not least interesting of the findings, 50% of the patients with musculoskeletal adverse events had a favorable response to the checkpoint inhibitor therapy, compared with just 12.5% of patients without these complaints, a difference that reached statistical significance (P = .0016), according to Dr. Filippopoulou. This observation is consistent with a study published last year that also associated immune-related adverse events with a greater likelihood of an anticancer response (Ann Rheumatic Dis. 2018;77:393-8).

“This is an interesting finding, but the theory that musculoskeletal adverse events predict a better response to checkpoint inhibitor therapy needs to be proven,” she said.

A larger case series is needed to better characterize joint inflammation associated with checkpoint inhibitors, but Dr. Filippopoulou concluded from her series that these adverse events are not accurately described as RA like. Rather, the phenotypic expression appears to be unique, not fully resembling any other joint pathology.

Dr. Filippopoulou reported no potential conflicts of interest.

SOURCE: Filippopoulou A et al. Ann Rheum Dis. Jun 2019;78 (Suppl 2):251. Abstract OP0335. doi: 10.1136/annrheumdis-2019-eular.5029.

MADRID – The musculoskeletal complications of checkpoint inhibitors therapy are sometimes described as RA like, but a detailed analysis of a consecutive series of patients presented at the European Congress of Rheumatology produced the conclusion that the phenotypic expression is unique.

“These manifestations do not necessarily include synovial involvement, so their description as a rheumatoid arthritis–like presentation is not accurate. Rather, our findings suggest the pathology is something completely different and completely new,” said Alexandra Filippopoulou, MD, a rheumatology resident at the University of Patras (Greece).

This comment was based on a prospective study evaluating musculoskeletal complications in patients treated with checkpoint inhibitors over a recent 2-year period. Of the 130 consecutive patients who received a checkpoint inhibitor in the study period, 10 (7.7%) complained of joint pain and were determined to have an inflammatory complication.

The median time to development of musculoskeletal symptoms in this mostly male patient series was 2.5 months. The site of cancer was lung in four, bladder in three, kidney in two, and skin in one. Nivolumab (Opdivo) was the most common checkpoint inhibitor used, but others were represented.

MRI studies were conducted in 8 of the 10 patients. Overall, the MRI studies showed more myofascial than synovial involvement, but Dr. Filippopoulou described three distinct patterns.

In four patients, there was prominent periarticular involvement marked by diffuse swelling in the hands, feet, knees, or a combination of these joints. Synovitis, when observed, was mild, but myositis and fasciitis were common in adjacent tissues.

In three patients with a chief complaint of knee pain, myofasciitis was prominent in the surrounding muscles. Again, synovitis, when observed, was mild. It was unclear whether a partial tear of the quadriceps tendon observed in one patient was checkpoint inhibitor related.

In a third pattern, shared by three other patients, synovitis was prominent, but so was myositis in adjacent muscles. In two of these patients, the inflammatory activity was confined to the hands; in the third, both the knees and the ankle were also involved.


Regardless of these patterns of inflammation, “almost all of these patients continued to show good range of motion, which is not something that is commonly seen in patients with rheumatoid arthritis,” Dr. Filippopoulou observed.

Overall, the joint pain tended to be mild to moderate. They all responded well to low-dose glucocorticoids or analgesics without need to discontinue the anticancer therapy, Dr. Filippopoulou reported.

Not least interesting of the findings, 50% of the patients with musculoskeletal adverse events had a favorable response to the checkpoint inhibitor therapy, compared with just 12.5% of patients without these complaints, a difference that reached statistical significance (P = .0016), according to Dr. Filippopoulou. This observation is consistent with a study published last year that also associated immune-related adverse events with a greater likelihood of an anticancer response (Ann Rheumatic Dis. 2018;77:393-8).

“This is an interesting finding, but the theory that musculoskeletal adverse events predict a better response to checkpoint inhibitor therapy needs to be proven,” she said.

A larger case series is needed to better characterize joint inflammation associated with checkpoint inhibitors, but Dr. Filippopoulou concluded from her series that these adverse events are not accurately described as RA like. Rather, the phenotypic expression appears to be unique, not fully resembling any other joint pathology.

Dr. Filippopoulou reported no potential conflicts of interest.

SOURCE: Filippopoulou A et al. Ann Rheum Dis. Jun 2019;78 (Suppl 2):251. Abstract OP0335. doi: 10.1136/annrheumdis-2019-eular.5029.

MADRID – The musculoskeletal complications of checkpoint inhibitors therapy are sometimes described as RA like, but a detailed analysis of a consecutive series of patients presented at the European Congress of Rheumatology produced the conclusion that the phenotypic expression is unique.

“These manifestations do not necessarily include synovial involvement, so their description as a rheumatoid arthritis–like presentation is not accurate. Rather, our findings suggest the pathology is something completely different and completely new,” said Alexandra Filippopoulou, MD, a rheumatology resident at the University of Patras (Greece).

This comment was based on a prospective study evaluating musculoskeletal complications in patients treated with checkpoint inhibitors over a recent 2-year period. Of the 130 consecutive patients who received a checkpoint inhibitor in the study period, 10 (7.7%) complained of joint pain and were determined to have an inflammatory complication.

The median time to development of musculoskeletal symptoms in this mostly male patient series was 2.5 months. The site of cancer was lung in four, bladder in three, kidney in two, and skin in one. Nivolumab (Opdivo) was the most common checkpoint inhibitor used, but others were represented.

MRI studies were conducted in 8 of the 10 patients. Overall, the MRI studies showed more myofascial than synovial involvement, but Dr. Filippopoulou described three distinct patterns.

In four patients, there was prominent periarticular involvement marked by diffuse swelling in the hands, feet, knees, or a combination of these joints. Synovitis, when observed, was mild, but myositis and fasciitis were common in adjacent tissues.

In three patients with a chief complaint of knee pain, myofasciitis was prominent in the surrounding muscles. Again, synovitis, when observed, was mild. It was unclear whether a partial tear of the quadriceps tendon observed in one patient was checkpoint inhibitor related.

In a third pattern, shared by three other patients, synovitis was prominent, but so was myositis in adjacent muscles. In two of these patients, the inflammatory activity was confined to the hands; in the third, both the knees and the ankle were also involved.


Regardless of these patterns of inflammation, “almost all of these patients continued to show good range of motion, which is not something that is commonly seen in patients with rheumatoid arthritis,” Dr. Filippopoulou observed.

Overall, the joint pain tended to be mild to moderate. They all responded well to low-dose glucocorticoids or analgesics without need to discontinue the anticancer therapy, Dr. Filippopoulou reported.

Not least interesting of the findings, 50% of the patients with musculoskeletal adverse events had a favorable response to the checkpoint inhibitor therapy, compared with just 12.5% of patients without these complaints, a difference that reached statistical significance (P = .0016), according to Dr. Filippopoulou. This observation is consistent with a study published last year that also associated immune-related adverse events with a greater likelihood of an anticancer response (Ann Rheumatic Dis. 2018;77:393-8).

“This is an interesting finding, but the theory that musculoskeletal adverse events predict a better response to checkpoint inhibitor therapy needs to be proven,” she said.

A larger case series is needed to better characterize joint inflammation associated with checkpoint inhibitors, but Dr. Filippopoulou concluded from her series that these adverse events are not accurately described as RA like. Rather, the phenotypic expression appears to be unique, not fully resembling any other joint pathology.

Dr. Filippopoulou reported no potential conflicts of interest.

SOURCE: Filippopoulou A et al. Ann Rheum Dis. Jun 2019;78 (Suppl 2):251. Abstract OP0335. doi: 10.1136/annrheumdis-2019-eular.5029.

MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.

“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.

In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.

Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.

“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.

In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.

In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.

When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.

Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.

In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.

Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.

These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.

“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.

These data are a first step.

“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)178-179.

MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.

“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.

In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.

Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.

“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.

In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.

In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.

When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.

Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.

In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.

Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.

These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.

“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.

These data are a first step.

“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)178-179.

MADRID – Administration of live attenuated booster of the MMR vaccine with or without varicella (MMR/V) was not associated with serious adverse events in children on immunosuppressive therapy for a rheumatic disease, according to data presented at the European Congress of Rheumatology.

“The study implies that patients can receive booster vaccinations regardless of age, diagnosis, or therapy,” reported Veronica Bergonzo Moshe, MD, a pediatric rheumatologist at Meir Medical Center, Kfar Saba, Israel.

In the absence of safety data, the vaccination of children with rheumatic diseases taking immunosuppressive therapies has been controversial. Although these children face communicable and sometimes life-threatening diseases without vaccination, many clinicians are not offering this protection because they fear adverse consequences.

Current Paediatric Rheumatology European Society (PReS) guidelines have been equivocal, recommending that vaccines be considered on a “case-by-case basis” in children with a rheumatic disease if they are taking high doses of disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or any dose of biologics.

“The fear is that a state of immune suppression might decrease response to the vaccine or lead to a flare of the rheumatologic disease,” Dr. Moshe said.

In the retrospective study presented by Dr. Moshe, data were collected on 234 children with rheumatic diseases who received a live attenuated MMR/V booster. The children were drawn from 12 pediatric rheumatology centers in 10 countries.

In this relatively large series, 82% of the children had oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). A range of other rheumatic diseases, including juvenile dermatomyositis, localized scleroderma, and isolated idiopathic uveitis were represented among the remaining patients. All were taking medication, and 48% were in remission.

When broken down by therapy, there were three localized reactions in 110 (2.7%) children who received the booster while on methotrexate. No other adverse events, including disease flare, were observed.

Similarly, six of the seven adverse events observed in 76 (8%) patients who were taking methotrexate plus a tumor necrosis factor (TNF) inhibitor biologic at the time of vaccination were local reactions. Fever was reported in one patient. All of these events were transient.

In the 39 patients taking a TNF inhibitor alone, there was a single case of transient fever. There were no adverse events reported in the three patients vaccinated while on tocilizumab, seven patients while on anakinra, or five patients while on canakinumab.

Following vaccination, there were no signs of symptoms of the diseases that the vaccines are designed to prevent. In the minority of patients who did develop localized reactions or fever in this series, there was no apparent relationship with disease activity, age, or sex when compared to those who did not develop an adverse event.

These retrospective data are not definitive, but they are reassuring, according to Dr. Moshe. A larger prospective study by the PReS vaccination study group is now planned. The issue of leaving children unvaccinated is topical due to the recent outbreaks of measles in the United States.

“We must have clear guidelines on how to deal with the administration of live vaccines in this patient population so that we can provide the safest and most effective practice,” Dr. Moshe said.

These data are a first step.

“This large retrospective study demonstrates that live attenuated booster vaccine is probably safe in children with rheumatic diseases,” said Dr. Moshe, but she deferred to the PReS guidelines in suggesting that the decision to vaccinate still might best be performed on a case-by-case basis.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)178-179.

MADRID – Retreatment of rheumatoid arthritis (RA) with an ultra low-dose of rituximab failed to meet the predefined noninferiority endpoint relative to a higher dose in a double-blind randomized trial, but the investigators still think this strategy may be viable in selected patients.

Lise M. Verhoef, MSc, a researcher in rheumatology at the Sint Maartenskliniek in Nijmegen, the Netherlands, who presented the data as a late-breaker at the European Congress of Rheumatology, explains in a video interview why the negative trial still might support an ultra low-dose strategy.

This trial, called REDO, was conceived after it was observed that most patients with RA are well controlled on a single injection of 1,000 mg of rituximab even though this is half the standard dose of two 1,000 mg doses given 15 days apart. The study was designed to determine whether even lower doses could be used.

The study enrolled 142 patients with RA who were being retreated with rituximab after responding previously to this therapy. In a 1:2:2 ratio, patients were randomized to single rituximab injections of 1,000 mg, 500 mg, or 200 mg. Outcome then were compared at the end of 6 months.

Noninferiority was defined as 0.5 difference in DAS28-CRP score (disease activity score using C-reactive protein instead of erythrocyte sedimentation rate) score adjusted for baseline disease status and use of conventional disease-modifying antirheumatic drugs (DMARDs).

Although noninferior at 3 months, the 500 mg dose did not meet the noninferiority criteria at 6 months. Due to a hierarchical design, evaluation of the 200 mg dose was precluded by the negative result with the 500 mg dose.

However, the majority of patients did respond to both the 500 mg and 200 mg dose. The failure to meet noninferiority was due to a limited number of patients who required rescue therapy for a flare. As a result, the investigators believe a trial of ultra low-dose therapy still might be reasonable.

In this interview, Ms. Verhoef explains that at her center patients who are well controlled on a 1,000 mg dose of rituximab now are being offered a 500 mg dose for retreatment. If they continue to respond, further retreatment with a 200 mg dose is considered.

Ms. Verhoef had no relevant financial disclosures.

MADRID – Retreatment of rheumatoid arthritis (RA) with an ultra low-dose of rituximab failed to meet the predefined noninferiority endpoint relative to a higher dose in a double-blind randomized trial, but the investigators still think this strategy may be viable in selected patients.

Lise M. Verhoef, MSc, a researcher in rheumatology at the Sint Maartenskliniek in Nijmegen, the Netherlands, who presented the data as a late-breaker at the European Congress of Rheumatology, explains in a video interview why the negative trial still might support an ultra low-dose strategy.

This trial, called REDO, was conceived after it was observed that most patients with RA are well controlled on a single injection of 1,000 mg of rituximab even though this is half the standard dose of two 1,000 mg doses given 15 days apart. The study was designed to determine whether even lower doses could be used.

The study enrolled 142 patients with RA who were being retreated with rituximab after responding previously to this therapy. In a 1:2:2 ratio, patients were randomized to single rituximab injections of 1,000 mg, 500 mg, or 200 mg. Outcome then were compared at the end of 6 months.

Noninferiority was defined as 0.5 difference in DAS28-CRP score (disease activity score using C-reactive protein instead of erythrocyte sedimentation rate) score adjusted for baseline disease status and use of conventional disease-modifying antirheumatic drugs (DMARDs).

Although noninferior at 3 months, the 500 mg dose did not meet the noninferiority criteria at 6 months. Due to a hierarchical design, evaluation of the 200 mg dose was precluded by the negative result with the 500 mg dose.

However, the majority of patients did respond to both the 500 mg and 200 mg dose. The failure to meet noninferiority was due to a limited number of patients who required rescue therapy for a flare. As a result, the investigators believe a trial of ultra low-dose therapy still might be reasonable.

In this interview, Ms. Verhoef explains that at her center patients who are well controlled on a 1,000 mg dose of rituximab now are being offered a 500 mg dose for retreatment. If they continue to respond, further retreatment with a 200 mg dose is considered.

Ms. Verhoef had no relevant financial disclosures.

MADRID – Retreatment of rheumatoid arthritis (RA) with an ultra low-dose of rituximab failed to meet the predefined noninferiority endpoint relative to a higher dose in a double-blind randomized trial, but the investigators still think this strategy may be viable in selected patients.

Lise M. Verhoef, MSc, a researcher in rheumatology at the Sint Maartenskliniek in Nijmegen, the Netherlands, who presented the data as a late-breaker at the European Congress of Rheumatology, explains in a video interview why the negative trial still might support an ultra low-dose strategy.

This trial, called REDO, was conceived after it was observed that most patients with RA are well controlled on a single injection of 1,000 mg of rituximab even though this is half the standard dose of two 1,000 mg doses given 15 days apart. The study was designed to determine whether even lower doses could be used.

The study enrolled 142 patients with RA who were being retreated with rituximab after responding previously to this therapy. In a 1:2:2 ratio, patients were randomized to single rituximab injections of 1,000 mg, 500 mg, or 200 mg. Outcome then were compared at the end of 6 months.

Noninferiority was defined as 0.5 difference in DAS28-CRP score (disease activity score using C-reactive protein instead of erythrocyte sedimentation rate) score adjusted for baseline disease status and use of conventional disease-modifying antirheumatic drugs (DMARDs).

Although noninferior at 3 months, the 500 mg dose did not meet the noninferiority criteria at 6 months. Due to a hierarchical design, evaluation of the 200 mg dose was precluded by the negative result with the 500 mg dose.

However, the majority of patients did respond to both the 500 mg and 200 mg dose. The failure to meet noninferiority was due to a limited number of patients who required rescue therapy for a flare. As a result, the investigators believe a trial of ultra low-dose therapy still might be reasonable.

In this interview, Ms. Verhoef explains that at her center patients who are well controlled on a 1,000 mg dose of rituximab now are being offered a 500 mg dose for retreatment. If they continue to respond, further retreatment with a 200 mg dose is considered.

Ms. Verhoef had no relevant financial disclosures.

MADRID – Patients achieve comparable long-term control of spondyloarthritis on biosimilars as they do on the originator biologic drug, judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.

Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).

In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.

As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.

Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.

Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.

In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.

Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.

MADRID – Patients achieve comparable long-term control of spondyloarthritis on biosimilars as they do on the originator biologic drug, judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.

Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).

In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.

As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.

Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.

Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.

In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.

Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.

MADRID – Patients achieve comparable long-term control of spondyloarthritis on biosimilars as they do on the originator biologic drug, judging from data drawn from registries in five Scandinavian countries in a study that evaluated retention rates after 1 year of therapy.

Bente Glintborg, MD, PhD, from the Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, explains in a video interview that the indication provided to biosimilars for spondyloarthritis was extended from comparisons conducted in rheumatoid arthritis (RA).

In the absence of a randomized trial in spondyloarthritis, she suggested that this comparison might be the best opportunity to evaluate whether biosimilars perform as well as their biologic originator. This is an important aim based on the theoretical possibility that equivalence in RA does not translate into equivalence in other rheumatic conditions where biologics are indicated.

As she explains, 1,015 biologic-naïve patients initiating etanercept, a tumor necrosis factor (TNF) inhibitor, or a biosimilar were assessed at baseline and at the end of 1 year of therapy. The patients were enrolled in biologic registries maintained in Denmark, Finland, Iceland, Norway, or Sweden.

Retention rates at 1 year were numerically lower on etanercept than the biosimilars, but the difference was not significant (66% vs. 73%; P = 0.18). There also were no significant differences between the biosimilars and etanercept when disease activity was compared at 6 months.

Retention rates are a reasonable surrogate for both efficacy and tolerability based on the expectation that more patients would switch or discontinue agents in the event of lack of efficacy or unacceptable side effects, Dr. Glintborg said at the European Congress of Rheumatology.

In this interview, she notes that a similar study from the Nordic registries led by a coinvestigator also showed equivalent retention rates among spondyloarthritis patients when biosimilars and infliximab were compared at 2 years.

Dr. Glintborg received research support from Biogen, Pfizer, and Abbievie.

MADRID – A video-based educational program on the goals of treatment in rheumatoid arthritis (RA) is showing promise as a tool to engage patients in their own care, according to data generated from a randomized trial.

One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.

Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.

For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.

To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).

Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.

Dr. Danila received research support from Pfizer.

MADRID – A video-based educational program on the goals of treatment in rheumatoid arthritis (RA) is showing promise as a tool to engage patients in their own care, according to data generated from a randomized trial.

One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.

Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.

For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.

To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).

Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.

Dr. Danila received research support from Pfizer.

MADRID – A video-based educational program on the goals of treatment in rheumatoid arthritis (RA) is showing promise as a tool to engage patients in their own care, according to data generated from a randomized trial.

One of the major goals of the video program is to inform patients about the treat-to-target concept of RA management, explained Maria I. Danila, MD, a rheumatologist at the University of Alabama at Birmingham.

Although physicians know this to be a guiding tenet for RA management, she explains in this video interview that 50% or more of patients are unaware of this therapeutic goal.

For patients who resist treatment escalation for fear of side effects, this lack of awareness might provide one explanation for failing to adhere to guideline-recommended therapy, Dr. Danila said at the European Congress of Rheumatology. She believes that patients need more information about the potential for treatment escalation to improve function.

To address this issue, a short video was developed to explain the treat-to-target concept. It was then tested in a randomized trial. Those who viewed the video expressed greater willingness to change intervention on the advice of their rheumatologist relative to those who did not (P = 0.01).

Further studies are planned, including studies to test whether willingness to escalate treatment results in better outcomes and whether linking patient behavioral goals such as being able to play golf again will enhance treatment adherence. Dr. Danila envisions wide distribution of this video if further studies demonstrate that it helps patients cooperate with treatment escalation when needed.

Dr. Danila received research support from Pfizer.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – EULAR has issued recommendations to help rheumatologists address the increasingly common clinical issue of diagnosing and managing rheumatic-related adverse events associated with cancer immunotherapy.

Gianluca Colla

“The rheumatic adverse events associated with immunotherapy represent a spectrum of new clinical entities, and they are challenging because they can be difficult to control while attempting to preserve the antitumor effects of oncological drugs,” Marie Kostine, MD, of the Centre Universitaire Hospitalier, Bordeaux, France, explained at the European Congress of Rheumatology.

The recommendations were drawn from the deliberations of an expert task force that identified the clinical issues to address and then developed a consensus about best practice recommendations. In addition to rheumatologists with expertise in this field, the task force included oncologists, allied health personnel, and two patient representatives.

The recommendations include four overarching principles and 10 recommendations.

“One of the overarching principles regards the importance of shared decision making between rheumatologists, oncologists, and patients,” Dr. Kostine said. Because of the expertise of rheumatologists in employing immunomodulatory therapies as they pertain to inflammation of the joints, the recommendations emphasize the value of their collaboration in clinical decisions.

The recommendations address patient referral, the assessment of preexisting rheumatic conditions, diagnosis, and therapeutic strategies.

“Rheumatologists should make themselves aware of the wide spectrum of potential clinical presentations of rheumatic adverse events following the initiation of immunotherapy,” Dr. Kostine said. While rheumatoid arthritis–like symptoms are common, the immune activation produced by checkpoint inhibitors and other immunotherapies can affect nearly every organ in the body, which includes diverse involvement of joint tissues.

In addition to joint pain, which has occurred in up to 40% of patients receiving a checkpoint inhibitor in some series, rheumatology-related events can include vasculitis, systemic sclerosis, and lupus. When associated with immunotherapy, these events sometimes develop in the absence of inflammatory markers or autoantibodies.

The new consensus guidelines emphasize that glucocorticoids can be “considered” to control rheumatic-related adverse events despite their immunosuppressive effect. However, because of their potential to attenuate the benefit of immune activation for treatment of the oncologic disease, such drugs, if used, “should be tapered to the lowest effective dose.”

The consensus recommendations were based on an extensive literature review, but Dr. Kostine acknowledged that prospective studies regarding the best practices for managing rheumatic-related adverse events of immunotherapies remain limited. She suggested that this knowledge gap was one reason for creating an expert task force.

“There has been an immunotherapy revolution, such that rheumatologists who have not yet seen these adverse events soon will,” said Dr. Kostine, noting that the number of approved immunotherapies and their clinical indications have been increasing rapidly.

The EULAR recommendations were created specifically for rheumatologists. In addition to guiding them toward best practice, the report from the task force provides background on the clinical issues raised by therapies that cause inflammatory side effects while stimulating immune function to treat malignancy.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl 2):158.

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – An observational study that includes adults and children with cryopyrin-associated periodic syndromes and related diseases has provided real-world evidence that clinical improvement accrues on canakinumab (Ilaris) years after treatment was initiated, according to Norbert Blank, MD, of the division of rheumatology at the University of Heidelberg (Germany).

Summarizing data he presented at the European Congress of Rheumatology, Dr. Blank explained in an interview that the observational study has accrued more than 50 patients so far, with the goal of reaching 300 patients with cryopyrin-associated periodic syndromes and related rare diseases that have responded to anti–interleukin-1 therapy, such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and familial Mediterranean fever.

Most of the patients participating in the observational study, called RELIANCE, were already on canakinumab at the time of enrollment, often for several years. Yet in follow-up so far – which exceeds 1 year for some of the participants – improvement from the time of entry has been seen for some outcomes, such as activity level, according to Dr. Blank.

Canakinumab has been well tolerated with no new or unexpected adverse events emerging in the follow-up so far. Although these data remain limited, Dr. Blank considers them reassuring.

With detailed characterization of these rare diseases at baseline, observational studies like RELIANCE provide valuable real-world data about disease presentation, according to Dr. Blank. He believes that further follow-up will provide a rich source of information about disease course in response to anti-IL-1 therapy, which is being individualized according to response.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – The glucagonlike peptide–1 receptor agonist liraglutide appears to be effective for keeping weight off following an intensive weight-loss program in patients with knee osteoarthritis, according to a randomized, double-blind, placebo-controlled trial presented at the European Congress of Rheumatology.

However, even though the 8-week intensive dietary program led to substantial weight loss and significant improvement in pain, additional weight loss of nearly 2.5 kg over 52 weeks of daily liraglutide treatment did not translate into more pain control.

According to study author Lars Erik Kristensen, MD, PhD, this is the first randomized trial to test the ability of liraglutide to provide a sustained weight loss in OA patients. The Food and Drug Administration indication for liraglutide is as an adjunct to diet and exercise for glycemic control in type 2 diabetes mellitus.

The study compared liraglutide against placebo in patients who had completed an intensive weight-control program in which the median loss was 12.46 kg. They were followed for 52 weeks.

At the end of follow-up, patients in the placebo group had gained a mean of 1.17 kg while those randomized to liraglutide lost an additional 2.76 kg. The between-group difference of 3.93 kg was statistically significant (P = .008).

“We believe that liraglutide is a promising agent for sustained weight loss in OA patients,” concluded Dr. Kristensen, a clinical researcher in rheumatology in the Parker Institute at Bispebjerg-Frederiksberg Hospital in Copenhagen.

In the single-center study, 156 patients were enrolled and randomized. In an initial 8-week diet intervention undertaken by both groups, an intensive program for weight loss included average daily calorie intakes of less than 800 kcal along with dietetic counseling. Patients were monitored for daily activities.

The majority of patients achieved a 10% or greater loss of total body weight during the intensive program before initiating 3 mg of once-daily liraglutide or a placebo.

Over the course of 52 weeks, the attrition from the study was relatively low. Among the 80 patients randomized to liraglutide, only 2 were lost because of noncompliance. Another 12 participants left the study before completion, 10 of whom did so for treatment-associated adverse effects. In the placebo arm, four patients were noncompliant, four left for treatment-associated adverse effects, and five left for other reasons.

Following the 8-week intensive dietary program, there was 11.86-point improvement in the pain subscale of the Knee and Osteoarthritis Outcome Score, confirming a substantial symptomatic benefit from this degree of weight loss. While this improvement in pain score was sustained at 52 weeks in both groups, the additional weight loss in the liraglutide arm did not lead to additional pain control.

The lack of additional pain control in the liraglutide group was disappointing, and the reason is unclear, but Dr. Kristensen emphasized that the persistent improvement in pain control was a positive result. In patients who are overweight or obese, regardless of whether they have concomitant OA, weight loss is not only difficult to achieve but difficult to sustain even after a successful intervention.

Dr. Kristensen reported financial relationships with multiple pharmaceutical companies. The trial received funding from Novo Nordisk.

SOURCE: Kristensen LE et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):71-2. Abstract OP0011. doi: 10.1136/annrheumdis-2019-eular.1375.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.

MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).

In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.

As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.


Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.

For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.

In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.

SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.