EULAR (European League Against Rheumatism): 2018 Congress

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

Ted Bosworth/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

AMSTERDAM – The new systemic lupus erythematosus classification criteria of the American College of Rheumatology and the European League Against Rheumatism are based on a point system that will produce a “paradigm shift” in how the disease gets studied going forward, said Sindhu Johnson, MD, while presenting the latest version of the newly revised classification scheme at the European Congress of Rheumatology.

Until now, classification of systemic lupus erythematosus (SLE) was a yes-or-no decision, based on whether the patient had a minimum number of characteristic signs or symptoms. The new criteria, which are on track for formal endorsement before the end of 2018 by the two medical societies that sponsored the revision, instead use a point system that gives varying weight to each of the 22 criteria. A patient needs to score at least 10 points from these criteria, and all patients classified with SLE also must have an antinuclear antibody (ANA) titer of at least 1:80 on HEp-2 cells or an equivalent positive test. This means that the criteria also can define patients who just miss classification with SLE by meeting the ANA standard and by tallying 8 or 9 points, and the criteria also identify patients who far exceed the classification threshold by having the requisite ANA plus racking up as many as, perhaps, 20 or 30 points.

“This is a real research opportunity,” to follow patients who fall just short with 8 or 9 points to assess their longer-term prognosis, as well as to study whether “higher scores mean a higher risk for developing a bad outcome,” said Dr. Johnson, a rheumatologist at the University of Toronto and director of the Toronto Scleroderma Program. Other areas for future research with the new criteria include seeing how they work in various SLE subgroups, such as patients with renal-predominant disease or skin-predominant disease, and also seeing how they work in various ethnic populations.

That’s because “85% of our experts said that they would feel confident classifying a patient as having lupus based only on a renal biopsy” and ANA positivity, said Dr. Johnson, who served as the ACR-appointed cochair of the criteria-writing panel along with a cochair selected by EULAR, Martin Aringer, MD, PhD, of the Technical University of Dresden (Germany). She cautioned that other levels of lupus nephritis, class II or V, confer only 8 points to the classification and so by themselves are not enough to label a person as having lupus.

During her presentation, Dr. Johnson cited the high levels of sensitivity and specificity that the new classification criteria demonstrated in a validation cohort of more than 1,000 cases and controls. In the validation analysis, the new criteria had a sensitivity of 96.12% and specificity of 94.43% for classifying SLE, giving the new criteria a better result on both these measures than either the 1997 ACR criteria (Arthritis Rheum. 1997 Sept;40[9]:1725) or the 2012 Systemic Lupus International Collaborating Clinics criteria (Arthritis Rheum. 2012 Aug;64[8]:2677-86).

The 22 criteria cluster into seven separate clinical domains and three different immunologic domains. The point values assigned to each criterion range from 2 to 10 points.

Dr. Johnson had no disclosures.

mzoler@mdedge.com

AMSTERDAM – The new systemic lupus erythematosus classification criteria of the American College of Rheumatology and the European League Against Rheumatism are based on a point system that will produce a “paradigm shift” in how the disease gets studied going forward, said Sindhu Johnson, MD, while presenting the latest version of the newly revised classification scheme at the European Congress of Rheumatology.

Until now, classification of systemic lupus erythematosus (SLE) was a yes-or-no decision, based on whether the patient had a minimum number of characteristic signs or symptoms. The new criteria, which are on track for formal endorsement before the end of 2018 by the two medical societies that sponsored the revision, instead use a point system that gives varying weight to each of the 22 criteria. A patient needs to score at least 10 points from these criteria, and all patients classified with SLE also must have an antinuclear antibody (ANA) titer of at least 1:80 on HEp-2 cells or an equivalent positive test. This means that the criteria also can define patients who just miss classification with SLE by meeting the ANA standard and by tallying 8 or 9 points, and the criteria also identify patients who far exceed the classification threshold by having the requisite ANA plus racking up as many as, perhaps, 20 or 30 points.

“This is a real research opportunity,” to follow patients who fall just short with 8 or 9 points to assess their longer-term prognosis, as well as to study whether “higher scores mean a higher risk for developing a bad outcome,” said Dr. Johnson, a rheumatologist at the University of Toronto and director of the Toronto Scleroderma Program. Other areas for future research with the new criteria include seeing how they work in various SLE subgroups, such as patients with renal-predominant disease or skin-predominant disease, and also seeing how they work in various ethnic populations.

That’s because “85% of our experts said that they would feel confident classifying a patient as having lupus based only on a renal biopsy” and ANA positivity, said Dr. Johnson, who served as the ACR-appointed cochair of the criteria-writing panel along with a cochair selected by EULAR, Martin Aringer, MD, PhD, of the Technical University of Dresden (Germany). She cautioned that other levels of lupus nephritis, class II or V, confer only 8 points to the classification and so by themselves are not enough to label a person as having lupus.

During her presentation, Dr. Johnson cited the high levels of sensitivity and specificity that the new classification criteria demonstrated in a validation cohort of more than 1,000 cases and controls. In the validation analysis, the new criteria had a sensitivity of 96.12% and specificity of 94.43% for classifying SLE, giving the new criteria a better result on both these measures than either the 1997 ACR criteria (Arthritis Rheum. 1997 Sept;40[9]:1725) or the 2012 Systemic Lupus International Collaborating Clinics criteria (Arthritis Rheum. 2012 Aug;64[8]:2677-86).

The 22 criteria cluster into seven separate clinical domains and three different immunologic domains. The point values assigned to each criterion range from 2 to 10 points.

Dr. Johnson had no disclosures.

mzoler@mdedge.com

AMSTERDAM – The new systemic lupus erythematosus classification criteria of the American College of Rheumatology and the European League Against Rheumatism are based on a point system that will produce a “paradigm shift” in how the disease gets studied going forward, said Sindhu Johnson, MD, while presenting the latest version of the newly revised classification scheme at the European Congress of Rheumatology.

Until now, classification of systemic lupus erythematosus (SLE) was a yes-or-no decision, based on whether the patient had a minimum number of characteristic signs or symptoms. The new criteria, which are on track for formal endorsement before the end of 2018 by the two medical societies that sponsored the revision, instead use a point system that gives varying weight to each of the 22 criteria. A patient needs to score at least 10 points from these criteria, and all patients classified with SLE also must have an antinuclear antibody (ANA) titer of at least 1:80 on HEp-2 cells or an equivalent positive test. This means that the criteria also can define patients who just miss classification with SLE by meeting the ANA standard and by tallying 8 or 9 points, and the criteria also identify patients who far exceed the classification threshold by having the requisite ANA plus racking up as many as, perhaps, 20 or 30 points.

“This is a real research opportunity,” to follow patients who fall just short with 8 or 9 points to assess their longer-term prognosis, as well as to study whether “higher scores mean a higher risk for developing a bad outcome,” said Dr. Johnson, a rheumatologist at the University of Toronto and director of the Toronto Scleroderma Program. Other areas for future research with the new criteria include seeing how they work in various SLE subgroups, such as patients with renal-predominant disease or skin-predominant disease, and also seeing how they work in various ethnic populations.

That’s because “85% of our experts said that they would feel confident classifying a patient as having lupus based only on a renal biopsy” and ANA positivity, said Dr. Johnson, who served as the ACR-appointed cochair of the criteria-writing panel along with a cochair selected by EULAR, Martin Aringer, MD, PhD, of the Technical University of Dresden (Germany). She cautioned that other levels of lupus nephritis, class II or V, confer only 8 points to the classification and so by themselves are not enough to label a person as having lupus.

During her presentation, Dr. Johnson cited the high levels of sensitivity and specificity that the new classification criteria demonstrated in a validation cohort of more than 1,000 cases and controls. In the validation analysis, the new criteria had a sensitivity of 96.12% and specificity of 94.43% for classifying SLE, giving the new criteria a better result on both these measures than either the 1997 ACR criteria (Arthritis Rheum. 1997 Sept;40[9]:1725) or the 2012 Systemic Lupus International Collaborating Clinics criteria (Arthritis Rheum. 2012 Aug;64[8]:2677-86).

The 22 criteria cluster into seven separate clinical domains and three different immunologic domains. The point values assigned to each criterion range from 2 to 10 points.

Dr. Johnson had no disclosures.

mzoler@mdedge.com

AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.

This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.

Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).

The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.

One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).

Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).

Sara Freeman/MDedge News

SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.

AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.

This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.

Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).

The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.

One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).

Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).

Sara Freeman/MDedge News

SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.

AMSTERDAM – The first European League Against Rheumatism and American College of Rheumatology joint criteria for classifying systemic lupus erythematosus have a sensitivity and a specificity of more than 90%.

This is important because they improve upon the existing ACR and Systemic Lupus International Collaborating Clinics (SLICC) criteria, said Martin Aringer, MD, PhD, who cochaired the Steering Committee that produced the new classification criteria.

Most clinicians working with lupus are familiar with the 1997 ACR criteria for the classification of systemic lupus erythematosus (SLE), which “had a relatively simple structure,” Dr. Aringer said during the opening plenary abstract session at the European Congress of Rheumatology. These considered items such as the presence of malar or discoid rash, photosensitivity, oral ulcers and arthritis, among others. These had a high specificity but a lower sensitivity. The development of the SLICC criteria in 2012 improved upon the sensitivity of the ACR criteria (92%-99% vs. 77%-91%), but at a loss in specificity (74%–88% vs. 91%-96%).

The SLICC criteria introduced two novel ideas, said Dr. Aringer, professor of medicine and chief of the division of rheumatology at the Technical University of Dresden (Germany). The first was that there had to be at least one immunologic criterion met, and the second was that biopsy-proven lupus nephritis had to be present with antinuclear antibodies (ANA) and anti-DNA antibodies detected.

One of the goals in developing the joint EULAR/ACR criteria therefore was to try to maintain the respective sensitivity and specificity achieved with the SLICC and ACR criteria. One of the key things that the new criteria looked at was to see if ANA could be used as an entry criterion. Investigations involving more than 13,000 patients with SLE showed that it could, with a antibody titer threshold of 1:80, exhibit a sensitivity of 98% (Arthritis Care Res. 2018;70[3]:428-38). Another goal was to see if histology-proven nephritis was a stronger predictor of SLE than clinical factors, such as oral ulcers, and to identify items that would only be included if there was no other more likely explanation (Lupus. 2016;25[8]:805-11).

Draft SLE classification criteria were developed based on an expert Delphi process and included ANA as an entry criterion and weighted items according to the likelihood of being associated with lupus. Items considered included the presence and severity of lupus nephritis, serology and other antibody tests, skin and central nervous system involvement, and hematologic and immunologic criteria such as the presence of thrombocytopenia and low complement (C3 and/or C4).

Sara Freeman/MDedge News

SOURCE: Aringer M et al. Ann Rheum Dis. 2018;77(Suppl 2):60. Abstract OP0020.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

mzoler@mdedge.com

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

mzoler@mdedge.com

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

mzoler@mdedge.com

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.

This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.

In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.

Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.

It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.

AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.

This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.

In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.

Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.

It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.

AMSTERDAM – The attempt to determine whether biologics such as tumor necrosis factor inhibitors (TNFi) inhibit progression of ankylosing spondylitis has been pursued with observational studies, but these types of studies will never definitively answer the question, according to Robert B.M. Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The methodology is sensitive to a lot of measurement error, making the results spurious,” Dr. Landewé said in an interview, recapping remarks he made in a presentation at the European Congress of Rheumatology.

This was disappointing to many investigators, including several speaking in the same symposium where Dr. Landewé made his remarks. Randomized, controlled trials that employ serial radiographs to document changes in ankylosing spondylitis are expensive, making observational studies an attractive surrogate, but Dr. Landewé said such studies are associated with an inherent risk of residual confounding.

In addition, he believes the effect size of biologics on progression, if it exists at all, is likely to be subtle. In the observational studies that have concluded that there is protection, complicated statistical analyses have been typically employed to produce a significant finding.

Observational studies do have hypothesis-generating value, according to Dr. Landewé, but he cautioned that they produce “more questions than answers.” He also emphasized that the inflammation-related progression that leads to bone growth in ankylosing spondylitis is different than it is in the destructive inflammatory diseases, such as rheumatoid arthritis, where the issue is bone loss.

It is rational to assume that effective anti-inflammatory therapy would prevent progression of inflammatory diseases, but Dr. Landewé said in his presentation that this is the type of bias that undermines the value of observational studies for reaching objective conclusions. Unlike the results of a registered randomized, controlled trial, which will be known to be consistent or not with the underlying hypothesis, there is a strong risk that data in an observational study will be reworked until they produce the desired result.

AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.

“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.

SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.

AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.

“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.

SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.

AMSTERDAM – In patients with axial spondyloarthritis, new evidence presented at the European Congress of Rheumatology associated tumor necrosis factor inhibitor therapy with prevention of sacroiliac joint progression.

“We already know that biologics can decelerate progression in the spine. The goal of this analysis was to determine whether there is also reduced risk of progression in the sacroiliac joints,” reported Valeria Rios-Rodríguez, MD, of Charité University Clinic in Berlin.

SOURCE: Rios-Rodriguez V et al. Ann Rheum Dis. 2018;77(Suppl 2):62-3. Abstract OP0025.