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New agents may bring hope for SLE patients
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
SANDESTIN, FLA. – Several drugs approved for other conditions may also have good effect in patients with systemic lupus erythematosus, Michelle Petri, MD, said in an interview at the annual Congress of Clinical Rheumatology.
The molecules target several different disease pathways, said Dr. Petri, director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
Ustekinumab (Stelara) has accumulated the most data so far. A phase 2 study presented last fall at the annual meeting of the American College of Rheumatology found that it conferred significant benefits relative to placebo, including a 60% responder rate (29% better than placebo), a significantly lower flare rate, and improvements in musculoskeletal and mucocutaneous disease features. The rate of serious adverse events was acceptable (8.3% vs. 9.5% for placebo).
Baricitinib is also being investigated in SLE, Dr. Petri said. A phase 2 study conducted by Eli Lilly closed late last year and will be reported on June 13 at the European League Against Rheumatism’s opening plenary session (Wallace et al. EULAR 2018 abstract OP0019).
The three-armed, placebo-controlled study comprised 314 patients who were randomized to placebo or one of two baricitinib doses, given orally for 24 weeks. The primary outcome was remission of arthritis and/or rash as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Secondary endpoints included responder rate, change from baseline in the SLEDAI-2K, change in the Global Assessment of Disease Activity score, and pharmacokinetic measures.
Dr. Petri disclosed relationships with Amgen, Boston Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, and GlaxoSmithKline.
EXPERT ANALYSIS FROM CCR 18
Newer IgG4 testing proving effective in assessing patients
SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.
Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.
But she found that, on flow cytometry, 88% of the woman’s circulating B cells were positive for IgG4, so the woman was treated with rituximab to deplete these cells.
“When the B cells were gone, we had release of the IgG4 in the serum and now we could pick it up with nephelometry,” she said.
This missed IgG4 with nephelometry prompted researchers to turn to ELISPOT, a sensitive method to count antibody-secreting cells. The test works well by capturing the antibodies’ presence right after they’re secreted, before they can become lost to receptor binding or in other ways.
“This was a better assay to measure the IgG4 antibodies rather than nephelometry,” she said.
Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.
The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.
She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.
“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”
Dr. Khosroshahi had no relevant disclosures.
SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.
Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.
But she found that, on flow cytometry, 88% of the woman’s circulating B cells were positive for IgG4, so the woman was treated with rituximab to deplete these cells.
“When the B cells were gone, we had release of the IgG4 in the serum and now we could pick it up with nephelometry,” she said.
This missed IgG4 with nephelometry prompted researchers to turn to ELISPOT, a sensitive method to count antibody-secreting cells. The test works well by capturing the antibodies’ presence right after they’re secreted, before they can become lost to receptor binding or in other ways.
“This was a better assay to measure the IgG4 antibodies rather than nephelometry,” she said.
Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.
The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.
She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.
“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”
Dr. Khosroshahi had no relevant disclosures.
SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.
Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.
But she found that, on flow cytometry, 88% of the woman’s circulating B cells were positive for IgG4, so the woman was treated with rituximab to deplete these cells.
“When the B cells were gone, we had release of the IgG4 in the serum and now we could pick it up with nephelometry,” she said.
This missed IgG4 with nephelometry prompted researchers to turn to ELISPOT, a sensitive method to count antibody-secreting cells. The test works well by capturing the antibodies’ presence right after they’re secreted, before they can become lost to receptor binding or in other ways.
“This was a better assay to measure the IgG4 antibodies rather than nephelometry,” she said.
Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.
The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.
She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.
“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”
Dr. Khosroshahi had no relevant disclosures.
EXPERT ANALYSIS FROM CCR 18
VIDEO: Calming microglia might control fibromyalgia
SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
REPORTING FROM CCR 2018
VIDEO: Characteristic flora define intestinal microbiome in scleroderma
SANDESTIN, FLA. – Scleroderma patients appear to have a characteristic microbiome composition, which is consistent in samples taken around the world.
These patients showed decreased populations of beneficial commensal flora and increased populations of proinflammatory species, Elizabeth Volkmann, MD, said at the annual Congress of Clinical Rheumatology.
Furthermore, specific species seem to correlate with specific gastrointestinal symptoms, said Dr. Volkmann of the University of California, Los Angeles. “Features also unexpectedly overlap with the consortium typical for Crohn’s disease, a disease with both inflammatory and fibrosing phenotype,” she said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Her recent exploration of this topic included 17 patients with scleroderma and GI symptoms and 17 matched healthy controls (BMJ Open Gastro. 2017;3:e000134). Everyone underwent a bowel prep and colonoscopy, during which cecum and sigmoid mucosal lavage samples were obtained. Those samples underwent RNA sequencing.
In addition to quantifying the species present, Dr. Volkmann sought to associate populations with symptoms. The primary assessment tool was the GIT 2.0, which measures distention/bloating; diarrhea; fecal soilage; constipation; emotional well-being; and social functioning.
Similar to the findings in inflammatory disease states, scleroderma patients had decreased levels of commensal Clostridia, a class of Firmicutes that is established in early infancy and very important in the maintenance of gut homeostasis. They also showed a decreased proportion of Faecalibacterium, a genus with anti-inflammatory activity; this finding has been observed in patients with Crohn’s disease.
Patients also showed relative increases in pathobionts. These are potentially pathological organisms that, under normal circumstances, live symbiotically. Janet Chow, PhD, who coined the term in a 2011 paper, said these species are typically proinflammatory (Curr Opin Immunol. 2011 Aug; 23[4]:473-80).
“Organisms proposed as pathobionts are associated with chronic inflammatory conditions – unlike opportunistic pathogens, which often cause acute infections and are typically acquired from the environment or other parts of the body. In addition, pathobionts are innocuous to the host under normal conditions,” wrote Dr. Chow of the California Institute of Technology, Pasadena.
In Dr. Volkmann’s study, Bifidobacterium and Lactobacillus, which are usually reduced in proinflammatory disorders, were relatively abundant in patients, compared with controls.
She noted specific associations with both symptoms. Parabacteroides and Enterobacteriaceae were associated with increased constipation. Prevotella was associated with increased diarrhea and increased distention/bloating.
Her results are consistent with a Swedish study (Arthritis Res Ther. 2016 Nov 1;18[1]:278) and three Italian studies conducted in Rome, Milan, and Piacenza.
“It’s fascinating that we seem to be identifying a consistent microbiome profile for scleroderma patients,” Dr. Volkmann said.
Dr. Volkmann had no relevant financial disclosures.
SANDESTIN, FLA. – Scleroderma patients appear to have a characteristic microbiome composition, which is consistent in samples taken around the world.
These patients showed decreased populations of beneficial commensal flora and increased populations of proinflammatory species, Elizabeth Volkmann, MD, said at the annual Congress of Clinical Rheumatology.
Furthermore, specific species seem to correlate with specific gastrointestinal symptoms, said Dr. Volkmann of the University of California, Los Angeles. “Features also unexpectedly overlap with the consortium typical for Crohn’s disease, a disease with both inflammatory and fibrosing phenotype,” she said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Her recent exploration of this topic included 17 patients with scleroderma and GI symptoms and 17 matched healthy controls (BMJ Open Gastro. 2017;3:e000134). Everyone underwent a bowel prep and colonoscopy, during which cecum and sigmoid mucosal lavage samples were obtained. Those samples underwent RNA sequencing.
In addition to quantifying the species present, Dr. Volkmann sought to associate populations with symptoms. The primary assessment tool was the GIT 2.0, which measures distention/bloating; diarrhea; fecal soilage; constipation; emotional well-being; and social functioning.
Similar to the findings in inflammatory disease states, scleroderma patients had decreased levels of commensal Clostridia, a class of Firmicutes that is established in early infancy and very important in the maintenance of gut homeostasis. They also showed a decreased proportion of Faecalibacterium, a genus with anti-inflammatory activity; this finding has been observed in patients with Crohn’s disease.
Patients also showed relative increases in pathobionts. These are potentially pathological organisms that, under normal circumstances, live symbiotically. Janet Chow, PhD, who coined the term in a 2011 paper, said these species are typically proinflammatory (Curr Opin Immunol. 2011 Aug; 23[4]:473-80).
“Organisms proposed as pathobionts are associated with chronic inflammatory conditions – unlike opportunistic pathogens, which often cause acute infections and are typically acquired from the environment or other parts of the body. In addition, pathobionts are innocuous to the host under normal conditions,” wrote Dr. Chow of the California Institute of Technology, Pasadena.
In Dr. Volkmann’s study, Bifidobacterium and Lactobacillus, which are usually reduced in proinflammatory disorders, were relatively abundant in patients, compared with controls.
She noted specific associations with both symptoms. Parabacteroides and Enterobacteriaceae were associated with increased constipation. Prevotella was associated with increased diarrhea and increased distention/bloating.
Her results are consistent with a Swedish study (Arthritis Res Ther. 2016 Nov 1;18[1]:278) and three Italian studies conducted in Rome, Milan, and Piacenza.
“It’s fascinating that we seem to be identifying a consistent microbiome profile for scleroderma patients,” Dr. Volkmann said.
Dr. Volkmann had no relevant financial disclosures.
SANDESTIN, FLA. – Scleroderma patients appear to have a characteristic microbiome composition, which is consistent in samples taken around the world.
These patients showed decreased populations of beneficial commensal flora and increased populations of proinflammatory species, Elizabeth Volkmann, MD, said at the annual Congress of Clinical Rheumatology.
Furthermore, specific species seem to correlate with specific gastrointestinal symptoms, said Dr. Volkmann of the University of California, Los Angeles. “Features also unexpectedly overlap with the consortium typical for Crohn’s disease, a disease with both inflammatory and fibrosing phenotype,” she said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Her recent exploration of this topic included 17 patients with scleroderma and GI symptoms and 17 matched healthy controls (BMJ Open Gastro. 2017;3:e000134). Everyone underwent a bowel prep and colonoscopy, during which cecum and sigmoid mucosal lavage samples were obtained. Those samples underwent RNA sequencing.
In addition to quantifying the species present, Dr. Volkmann sought to associate populations with symptoms. The primary assessment tool was the GIT 2.0, which measures distention/bloating; diarrhea; fecal soilage; constipation; emotional well-being; and social functioning.
Similar to the findings in inflammatory disease states, scleroderma patients had decreased levels of commensal Clostridia, a class of Firmicutes that is established in early infancy and very important in the maintenance of gut homeostasis. They also showed a decreased proportion of Faecalibacterium, a genus with anti-inflammatory activity; this finding has been observed in patients with Crohn’s disease.
Patients also showed relative increases in pathobionts. These are potentially pathological organisms that, under normal circumstances, live symbiotically. Janet Chow, PhD, who coined the term in a 2011 paper, said these species are typically proinflammatory (Curr Opin Immunol. 2011 Aug; 23[4]:473-80).
“Organisms proposed as pathobionts are associated with chronic inflammatory conditions – unlike opportunistic pathogens, which often cause acute infections and are typically acquired from the environment or other parts of the body. In addition, pathobionts are innocuous to the host under normal conditions,” wrote Dr. Chow of the California Institute of Technology, Pasadena.
In Dr. Volkmann’s study, Bifidobacterium and Lactobacillus, which are usually reduced in proinflammatory disorders, were relatively abundant in patients, compared with controls.
She noted specific associations with both symptoms. Parabacteroides and Enterobacteriaceae were associated with increased constipation. Prevotella was associated with increased diarrhea and increased distention/bloating.
Her results are consistent with a Swedish study (Arthritis Res Ther. 2016 Nov 1;18[1]:278) and three Italian studies conducted in Rome, Milan, and Piacenza.
“It’s fascinating that we seem to be identifying a consistent microbiome profile for scleroderma patients,” Dr. Volkmann said.
Dr. Volkmann had no relevant financial disclosures.
REPORTING FROM CCR 18
VIDEO: Skin exam crucial in rheumatic diseases, expert says
SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.
In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.
After examining her skin, Dr. Femia became immediately concerned.
“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.
These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.
“That is a form of dermatomyositis that you cannot miss,” she said.
The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.
Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.
“We want to treat these patients aggressively in order to avoid this.”
SOURCE: Femia A. CCR 2018.
SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.
In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.
After examining her skin, Dr. Femia became immediately concerned.
“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.
These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.
“That is a form of dermatomyositis that you cannot miss,” she said.
The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.
Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.
“We want to treat these patients aggressively in order to avoid this.”
SOURCE: Femia A. CCR 2018.
SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.
In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.
After examining her skin, Dr. Femia became immediately concerned.
“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.
These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.
“That is a form of dermatomyositis that you cannot miss,” she said.
The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.
Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.
“We want to treat these patients aggressively in order to avoid this.”
SOURCE: Femia A. CCR 2018.
EXPERT ANALYSIS AT CCR 18
VIDEO: Researchers seek end to early corticosteroid use in AAV
SANDESTIN, FLA. – Clinicians have long wanted to avoid using corticosteroids in the treatment of ANCA-associated vasculitis (AAV). They’re drawing closer to getting their wish, said Christian Pagnoux, MD, of the department of internal medicine at Mount Sinai Hospital in Toronto.
The drugs have been a cornerstone in the treatments of these diseases – including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) – for decades, but they come at the price of osteoporosis, cardiovascular comorbidities, diabetes, increased infection risk, and other problems.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The emergence of newer therapies such as rituximab and complement C5a-blocker avacopan could mean less of a reliance on corticosteroids, Dr. Pagnoux said. The ongoing ADVOCATE trial is assessing the efficacy of avacopan with rituximab or cyclophosphamide, with or without a tapered dose of prednisone for the first 21 weeks.
“Whether we can use a lighter, briefer, shorter corticosteroid regimen for induction is really a burning question,” Dr. Pagnoux said. Avacopan “may totally replace corticosteroids in the very near future,” he said.
Another trial taking an intense look at winnowing corticosteroids from GPA and MPA treatment is the eagerly awaited PEXIVAS trial, an international effort of 700 patients that is the largest ever in AAV, Dr. Pagnoux said.
The primary endpoint in the trial is assessing plasma exchange versus no plasma exchange, but the use of corticosteroids is being assessed as well.
“The PEXIVAS [trial] may give you some additional information,” Dr. Pagnoux said. “Patients were not only randomized to receive plasma exchange or no plasma exchange, but they were also randomized to receive the standard regimen of corticosteroids with a slow taper ... or a much faster regimen with a much faster tapering of the corticosteroids.” The fast taper involves a steep drop every week, so that, after just 1 month, doses have fallen from 60 mg to 10 mg.
Dr. Pagnoux said he can imagine the day when corticosteroids can be completely eliminated from induction treatment for GPA and MPA. But he added there are studies looking at the efficacy and safety of the drugs in maintenance treatment even once they’re eliminated from induction, but at far lower doses.
“The good news is that it would only be 5 mg per day, for example.”
SOURCE: Pagnoux C. CCR 2018.
SANDESTIN, FLA. – Clinicians have long wanted to avoid using corticosteroids in the treatment of ANCA-associated vasculitis (AAV). They’re drawing closer to getting their wish, said Christian Pagnoux, MD, of the department of internal medicine at Mount Sinai Hospital in Toronto.
The drugs have been a cornerstone in the treatments of these diseases – including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) – for decades, but they come at the price of osteoporosis, cardiovascular comorbidities, diabetes, increased infection risk, and other problems.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The emergence of newer therapies such as rituximab and complement C5a-blocker avacopan could mean less of a reliance on corticosteroids, Dr. Pagnoux said. The ongoing ADVOCATE trial is assessing the efficacy of avacopan with rituximab or cyclophosphamide, with or without a tapered dose of prednisone for the first 21 weeks.
“Whether we can use a lighter, briefer, shorter corticosteroid regimen for induction is really a burning question,” Dr. Pagnoux said. Avacopan “may totally replace corticosteroids in the very near future,” he said.
Another trial taking an intense look at winnowing corticosteroids from GPA and MPA treatment is the eagerly awaited PEXIVAS trial, an international effort of 700 patients that is the largest ever in AAV, Dr. Pagnoux said.
The primary endpoint in the trial is assessing plasma exchange versus no plasma exchange, but the use of corticosteroids is being assessed as well.
“The PEXIVAS [trial] may give you some additional information,” Dr. Pagnoux said. “Patients were not only randomized to receive plasma exchange or no plasma exchange, but they were also randomized to receive the standard regimen of corticosteroids with a slow taper ... or a much faster regimen with a much faster tapering of the corticosteroids.” The fast taper involves a steep drop every week, so that, after just 1 month, doses have fallen from 60 mg to 10 mg.
Dr. Pagnoux said he can imagine the day when corticosteroids can be completely eliminated from induction treatment for GPA and MPA. But he added there are studies looking at the efficacy and safety of the drugs in maintenance treatment even once they’re eliminated from induction, but at far lower doses.
“The good news is that it would only be 5 mg per day, for example.”
SOURCE: Pagnoux C. CCR 2018.
SANDESTIN, FLA. – Clinicians have long wanted to avoid using corticosteroids in the treatment of ANCA-associated vasculitis (AAV). They’re drawing closer to getting their wish, said Christian Pagnoux, MD, of the department of internal medicine at Mount Sinai Hospital in Toronto.
The drugs have been a cornerstone in the treatments of these diseases – including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) – for decades, but they come at the price of osteoporosis, cardiovascular comorbidities, diabetes, increased infection risk, and other problems.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The emergence of newer therapies such as rituximab and complement C5a-blocker avacopan could mean less of a reliance on corticosteroids, Dr. Pagnoux said. The ongoing ADVOCATE trial is assessing the efficacy of avacopan with rituximab or cyclophosphamide, with or without a tapered dose of prednisone for the first 21 weeks.
“Whether we can use a lighter, briefer, shorter corticosteroid regimen for induction is really a burning question,” Dr. Pagnoux said. Avacopan “may totally replace corticosteroids in the very near future,” he said.
Another trial taking an intense look at winnowing corticosteroids from GPA and MPA treatment is the eagerly awaited PEXIVAS trial, an international effort of 700 patients that is the largest ever in AAV, Dr. Pagnoux said.
The primary endpoint in the trial is assessing plasma exchange versus no plasma exchange, but the use of corticosteroids is being assessed as well.
“The PEXIVAS [trial] may give you some additional information,” Dr. Pagnoux said. “Patients were not only randomized to receive plasma exchange or no plasma exchange, but they were also randomized to receive the standard regimen of corticosteroids with a slow taper ... or a much faster regimen with a much faster tapering of the corticosteroids.” The fast taper involves a steep drop every week, so that, after just 1 month, doses have fallen from 60 mg to 10 mg.
Dr. Pagnoux said he can imagine the day when corticosteroids can be completely eliminated from induction treatment for GPA and MPA. But he added there are studies looking at the efficacy and safety of the drugs in maintenance treatment even once they’re eliminated from induction, but at far lower doses.
“The good news is that it would only be 5 mg per day, for example.”
SOURCE: Pagnoux C. CCR 2018.
EXPERT ANALYSIS AT CCR 18
VIDEO: Let clinical scenario, not imaging, guide sarcoidosis treatment
SANDESTIN, FLA. – Don’t be a slave to imaging when evaluating the patient with sarcoidosis.
“Sometimes, the worst-looking patients [on imaging] have the best prognosis,” Daniel Culver, DO, said at the annual Congress of Clinical Rheumatology. Patients with Löfgren’s syndrome are a very good example of this tenet, he said in an interview. Scans can look alarming, with multiple widespread granulomas. But Löfgren’s is generally a benign condition, despite its threatening mien.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Instead of imaging, “Let two things drive your decision to treat: danger to an organ, and quality of life,” said Dr. Culver, a pulmonologist and director of the Sarcoidosis Center of Excellence at the Cleveland Clinic in Ohio; he is also president of the World Association for Sarcoidosis.
He agrees with a decision schema published in 2015 (Clin Chest Med. 2015;36[4]:751-67).
Six factors weigh in favor of treatment:
- Symptomatic disease.
- Impaired organ function.
- Disease endangering an organ.
- Progressive disease.
- Clear-cut disease activity.
- Low likelihood of remission.
These must be balanced – with patient input as the fulcrum – against five factors that favor conservative management:
- Minimal symptoms.
- Good organ function.
- Low risk of danger to organs.
- Inactive disease.
- Higher likelihood of remission.
The decision to embark on a treatment program, usually starting with a steroid-based regimen, can’t be taken lightly, Dr. Culver said. A 2017 study showed that steroids pose a cumulative risk of toxicities for sarcoidosis patients (Respir Med. 2017 Nov;132:9-14). Patients who started steroids faced more than a doubling in the risk of a toxic side effect by 96 months when compared with those who didn’t. But even short-term steroid use increased the risk of a toxicity, Dr. Culver said. The study noted that problems can begin to occur in as little as 1 month, at a cumulative dose as low as 1 g.
For patients who fall onto the “treat” side of the risk teeter-totter, Dr. Culver recommended starting with an initial course of prednisone at 20-30 mg daily for no more than 4 weeks. Responders can taper to less than 10 mg/day. Those who continue to do well can maintain low-dose prednisone for up to 12 months and then complete the taper. Patients who relapse can add an immune modulator (methotrexate, azathioprine, leflunomide, or mycophenolate).
Those who have an inadequate response to the initial prednisone course should then get an immune modulator. If they do well, that can be maintained; a second modulator can be brought on board if necessary.
For those who don’t respond at all to the initial prednisone course, it’s necessary to proceed immediately to an immunosuppressive regimen to prevent irreversible fibrosis.
Dr. Culver noted associations with multiple pharmaceutical companies, but said none were relevant to his talk.
SOURCE: Culver D. CCR 2018.
SANDESTIN, FLA. – Don’t be a slave to imaging when evaluating the patient with sarcoidosis.
“Sometimes, the worst-looking patients [on imaging] have the best prognosis,” Daniel Culver, DO, said at the annual Congress of Clinical Rheumatology. Patients with Löfgren’s syndrome are a very good example of this tenet, he said in an interview. Scans can look alarming, with multiple widespread granulomas. But Löfgren’s is generally a benign condition, despite its threatening mien.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Instead of imaging, “Let two things drive your decision to treat: danger to an organ, and quality of life,” said Dr. Culver, a pulmonologist and director of the Sarcoidosis Center of Excellence at the Cleveland Clinic in Ohio; he is also president of the World Association for Sarcoidosis.
He agrees with a decision schema published in 2015 (Clin Chest Med. 2015;36[4]:751-67).
Six factors weigh in favor of treatment:
- Symptomatic disease.
- Impaired organ function.
- Disease endangering an organ.
- Progressive disease.
- Clear-cut disease activity.
- Low likelihood of remission.
These must be balanced – with patient input as the fulcrum – against five factors that favor conservative management:
- Minimal symptoms.
- Good organ function.
- Low risk of danger to organs.
- Inactive disease.
- Higher likelihood of remission.
The decision to embark on a treatment program, usually starting with a steroid-based regimen, can’t be taken lightly, Dr. Culver said. A 2017 study showed that steroids pose a cumulative risk of toxicities for sarcoidosis patients (Respir Med. 2017 Nov;132:9-14). Patients who started steroids faced more than a doubling in the risk of a toxic side effect by 96 months when compared with those who didn’t. But even short-term steroid use increased the risk of a toxicity, Dr. Culver said. The study noted that problems can begin to occur in as little as 1 month, at a cumulative dose as low as 1 g.
For patients who fall onto the “treat” side of the risk teeter-totter, Dr. Culver recommended starting with an initial course of prednisone at 20-30 mg daily for no more than 4 weeks. Responders can taper to less than 10 mg/day. Those who continue to do well can maintain low-dose prednisone for up to 12 months and then complete the taper. Patients who relapse can add an immune modulator (methotrexate, azathioprine, leflunomide, or mycophenolate).
Those who have an inadequate response to the initial prednisone course should then get an immune modulator. If they do well, that can be maintained; a second modulator can be brought on board if necessary.
For those who don’t respond at all to the initial prednisone course, it’s necessary to proceed immediately to an immunosuppressive regimen to prevent irreversible fibrosis.
Dr. Culver noted associations with multiple pharmaceutical companies, but said none were relevant to his talk.
SOURCE: Culver D. CCR 2018.
SANDESTIN, FLA. – Don’t be a slave to imaging when evaluating the patient with sarcoidosis.
“Sometimes, the worst-looking patients [on imaging] have the best prognosis,” Daniel Culver, DO, said at the annual Congress of Clinical Rheumatology. Patients with Löfgren’s syndrome are a very good example of this tenet, he said in an interview. Scans can look alarming, with multiple widespread granulomas. But Löfgren’s is generally a benign condition, despite its threatening mien.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Instead of imaging, “Let two things drive your decision to treat: danger to an organ, and quality of life,” said Dr. Culver, a pulmonologist and director of the Sarcoidosis Center of Excellence at the Cleveland Clinic in Ohio; he is also president of the World Association for Sarcoidosis.
He agrees with a decision schema published in 2015 (Clin Chest Med. 2015;36[4]:751-67).
Six factors weigh in favor of treatment:
- Symptomatic disease.
- Impaired organ function.
- Disease endangering an organ.
- Progressive disease.
- Clear-cut disease activity.
- Low likelihood of remission.
These must be balanced – with patient input as the fulcrum – against five factors that favor conservative management:
- Minimal symptoms.
- Good organ function.
- Low risk of danger to organs.
- Inactive disease.
- Higher likelihood of remission.
The decision to embark on a treatment program, usually starting with a steroid-based regimen, can’t be taken lightly, Dr. Culver said. A 2017 study showed that steroids pose a cumulative risk of toxicities for sarcoidosis patients (Respir Med. 2017 Nov;132:9-14). Patients who started steroids faced more than a doubling in the risk of a toxic side effect by 96 months when compared with those who didn’t. But even short-term steroid use increased the risk of a toxicity, Dr. Culver said. The study noted that problems can begin to occur in as little as 1 month, at a cumulative dose as low as 1 g.
For patients who fall onto the “treat” side of the risk teeter-totter, Dr. Culver recommended starting with an initial course of prednisone at 20-30 mg daily for no more than 4 weeks. Responders can taper to less than 10 mg/day. Those who continue to do well can maintain low-dose prednisone for up to 12 months and then complete the taper. Patients who relapse can add an immune modulator (methotrexate, azathioprine, leflunomide, or mycophenolate).
Those who have an inadequate response to the initial prednisone course should then get an immune modulator. If they do well, that can be maintained; a second modulator can be brought on board if necessary.
For those who don’t respond at all to the initial prednisone course, it’s necessary to proceed immediately to an immunosuppressive regimen to prevent irreversible fibrosis.
Dr. Culver noted associations with multiple pharmaceutical companies, but said none were relevant to his talk.
SOURCE: Culver D. CCR 2018.
REPORTING FROM CCR 18
VIDEO: Dual studies seek answers in isolated skin vasculitis
SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.
“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).
That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”
ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.
ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.
The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.
To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.
Dr. Pagnoux had no financial disclosures relevant to either study.
SOURCE: Pagnoux C. CCR 2018
SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.
“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).
That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”
ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.
ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.
The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.
To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.
Dr. Pagnoux had no financial disclosures relevant to either study.
SOURCE: Pagnoux C. CCR 2018
SANDESTIN, FLA. – Patients with isolated skin vasculitis have always faced a frustrating clinical problem with no clear solution.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ARAMIS (A Randomized Multicenter Study for Isolated Skin Vasculitis) and its linked genetic investigation, CUTIS (Clinical Transcriptomics in Systemic Vasculitis), may finally identify not only optimal treatments but also insight into the root causes and predictors of treatment response, Christian Pagnoux, MD, said at the annual Congress of Clinical Rheumatology.
“Isolated skin vasculitis is a much-understudied disease, with only one clinical trial to guide our treatment,” said Dr. Pagnoux of the Mount Sinai Hospital, Toronto. In 1995, a 3-month trial randomized 41 patients to skin emollients or to colchicine 0.5 mg/day. Colchicine wasn’t significantly better, but some who had attained remission on it relapsed after discontinuing the drug, which suggested there might be some benefit (Arch Dermatol. 1995;131[12]:1399-1402).
That hint of efficacy in just three patients 23 years ago forms the sole basis of the typical treatment for this disorder: colchicine, Dr. Pagnoux said. “We know that it doesn’t work, yet we continue to prescribe it. Patients deserve better.”
ARAMIS and CUTIS are the first attempts since then at solving this puzzle. ARAMIS is now recruiting about 90 patients in 10 North American medical centers. The three-armed crossover trial will randomize patients to colchicine 0.6 mg twice a day, dapsone 150 mg/day, or azathioprine 2 mg/kg per day for 6 months. Nonresponders can then be rerandomized to one of the other two study drugs for another 6 months. The primary endpoint is clinical response. Secondary endpoints include changes in physician and patient global assessment of response, Skindex29 score, health-related quality of life, and the Patient-Reported Outcomes Measurement Information System.
ARAMIS patients may also participate in CUTIS, the linked histopathologic and genetic investigation. More broad-ranging than ARAMIS, CUTIS is seeking 50 patients with several forms of idiopathic vasculitis, including cryoglobulinemic vasculitis, drug-induced vasculitis, eosinophilic granulomatosis with polyangiitis, IgA vasculitis, isolated cutaneous vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, and urticarial vasculitis.
The study will examine histopathologic and transcriptomic characteristics in punch biopsies of the lesions. “We very much hope that gene expression profiling on these lesions will help define novel pathways and help us to classify and target therapies,” Dr. Pagnoux said.
To learn more about these studies and refer patients into them, visit the Rare Disease Network pages for ARAMIS and CUTIS.
Dr. Pagnoux had no financial disclosures relevant to either study.
SOURCE: Pagnoux C. CCR 2018
REPORTING FROM CCR 18
Even a year of increased water intake did not change CKD course
Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.
Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..
However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.
“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report
An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.
However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.
The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.
Patients in the hydration group were also given reusable drinking containers and 20 vouchers per month redeemable for 1.5 L of bottled water, investigators reported.
Urine volume did significantly increase in the hydration group versus controls, by 0.6 L per day (P less than .001). However, change in eGFR – the primary outcome – was not significantly different between groups. Mean change in eGFR was –2.2 mL/min per 1.73 m2 in patients coached to drink more water and –1.9 mL/min per 1.73 m2 in those coached to maintain water intake (P = .74).
Some secondary outcome measures demonstrated significant differences in favor of the hydration group. Plasma copeptin and creatinine clearance both showed significant differences in favor of the hydration group. In contrast, there were no significant differences between intervention arms in urine albumin or quality of health, according to analyses of secondary outcomes described in the study report.
There are several ways to interpret the finding that drinking more water had no effect on eGFR, investigators said. Increasing water intake may simply not be protective against kidney function decline. Perhaps follow-up longer than 1 year would be needed to see an effect, or perhaps there was an effect, but the study was underpowered to detect it.
It could also be that a greater volume of water would be needed to demonstrate a protective effect for the kidneys. Despite the coaching efforts of dietitians and research assistants, the mean urine volume increase in the hydration group relative to the control group was just 0.6 liter per day, or 2.4 cups.
“This highlights how difficult it would be to achieve a large sustained increase in water intake in routine practice,” Dr. Clark and colleagues said in their report.
Dr. Clark reported disclosures related to Danone Research. Thermo Fisher Scientific provided instrumentation, assay reagent, and disposables used in the study.
SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.
Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.
Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..
However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.
“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report
An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.
However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.
The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.
Patients in the hydration group were also given reusable drinking containers and 20 vouchers per month redeemable for 1.5 L of bottled water, investigators reported.
Urine volume did significantly increase in the hydration group versus controls, by 0.6 L per day (P less than .001). However, change in eGFR – the primary outcome – was not significantly different between groups. Mean change in eGFR was –2.2 mL/min per 1.73 m2 in patients coached to drink more water and –1.9 mL/min per 1.73 m2 in those coached to maintain water intake (P = .74).
Some secondary outcome measures demonstrated significant differences in favor of the hydration group. Plasma copeptin and creatinine clearance both showed significant differences in favor of the hydration group. In contrast, there were no significant differences between intervention arms in urine albumin or quality of health, according to analyses of secondary outcomes described in the study report.
There are several ways to interpret the finding that drinking more water had no effect on eGFR, investigators said. Increasing water intake may simply not be protective against kidney function decline. Perhaps follow-up longer than 1 year would be needed to see an effect, or perhaps there was an effect, but the study was underpowered to detect it.
It could also be that a greater volume of water would be needed to demonstrate a protective effect for the kidneys. Despite the coaching efforts of dietitians and research assistants, the mean urine volume increase in the hydration group relative to the control group was just 0.6 liter per day, or 2.4 cups.
“This highlights how difficult it would be to achieve a large sustained increase in water intake in routine practice,” Dr. Clark and colleagues said in their report.
Dr. Clark reported disclosures related to Danone Research. Thermo Fisher Scientific provided instrumentation, assay reagent, and disposables used in the study.
SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.
Coaching adults with stage 3 chronic kidney disease (CKD) to increase water intake did not significantly slow decline in kidney function, results of a randomized clinical trial show.
Compared with coaching to maintain water intake, coaching to increase water intake did in fact increase water intake but did not prevent a decrease in estimated glomerular filtration rate (eGFR) over 1 year, according to findings of the study, which was published in JAMA..
However, the study may have been underpowered to detect a clinically important difference in this primary endpoint, and certain secondary endpoints did suggest a favorable effect of the intervention, according to William F. Clark, MD, of the London (Ontario) Health Sciences Centre and his coauthors.
“The increased water intake achieved in this trial was sufficient to lower vasopressin secretion, as assessed by plasma copeptin concentrations,” Dr. Clark and his colleagues said in their report
An increasing number of studies suggest that drinking water may benefit the kidneys. In some human studies, water intake was associated with reduced risk of kidney stones and better kidney function.
However, it remains unknown whether increasing water intake would benefit patients with CKD. To evaluate this question, Dr. Clark and colleagues initiated CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial conducted in 9 centers in Ontario.
The study included 631 patients with stage 3 CKD and a 24-hour urine volume below 3 L. Patients randomized to the hydration group were coached to increase water intake gradually to 1-1.5 L/day for 1 year, while those randomized to the control group were coached to maintain their usual water intake.
Patients in the hydration group were also given reusable drinking containers and 20 vouchers per month redeemable for 1.5 L of bottled water, investigators reported.
Urine volume did significantly increase in the hydration group versus controls, by 0.6 L per day (P less than .001). However, change in eGFR – the primary outcome – was not significantly different between groups. Mean change in eGFR was –2.2 mL/min per 1.73 m2 in patients coached to drink more water and –1.9 mL/min per 1.73 m2 in those coached to maintain water intake (P = .74).
Some secondary outcome measures demonstrated significant differences in favor of the hydration group. Plasma copeptin and creatinine clearance both showed significant differences in favor of the hydration group. In contrast, there were no significant differences between intervention arms in urine albumin or quality of health, according to analyses of secondary outcomes described in the study report.
There are several ways to interpret the finding that drinking more water had no effect on eGFR, investigators said. Increasing water intake may simply not be protective against kidney function decline. Perhaps follow-up longer than 1 year would be needed to see an effect, or perhaps there was an effect, but the study was underpowered to detect it.
It could also be that a greater volume of water would be needed to demonstrate a protective effect for the kidneys. Despite the coaching efforts of dietitians and research assistants, the mean urine volume increase in the hydration group relative to the control group was just 0.6 liter per day, or 2.4 cups.
“This highlights how difficult it would be to achieve a large sustained increase in water intake in routine practice,” Dr. Clark and colleagues said in their report.
Dr. Clark reported disclosures related to Danone Research. Thermo Fisher Scientific provided instrumentation, assay reagent, and disposables used in the study.
SOURCE: Clark WF et al. JAMA. 2018;319(18):1870-9.
Key clinical point: Adults with CKD were coached to increase water intake, but that intervention did not appear to slow their decline in kidney function.
Major finding: The 1-year change in eGFR was –2.2 mL/min per 1.73 m2 in patients coached to drink more water and –1.9 mL/min per 1.73 m2 in those coached to maintain water intake; the difference was not significant.
Study details: The CKD WIT (Chronic Kidney Disease Water Intake Trial), a randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 and included 631 patients with stage 3 CKD and a 24-hour urine volume below 3.0 L.
Disclosures: Authors reported disclosures related to Danone Research and the ISN/Danone Hydration for Kidney Health Research Initiative. Thermo Fisher Scientific provided instrumentation, assay reagent, and disposables used in the study.
Source: Clark WF et al. JAMA. 2018;319(18):1870-9.
Heart disease in GPA exacts high toll in year 2 and beyond
LIVERPOOL, ENGLAND – Cardiovascular disease was the predominant cause of death of patients with granulomatosis with polyangiitis 1-5 years after a diagnosis in a study by U.K. researchers, suggesting that this could be a target for future intervention.
While active disease was the No. 1 cause of death within the first year of diagnosis in 40% of patients with granulomatosis with polyangiitis (GPA), it was overtaken by cardiovascular disease (CVD) as the main cause of death in 37.5% of patients in the next 4 years from diagnosis.
“The idea for this study came from patients with vasculitis who were polled by Vasculitis UK,” Fiona A. Pearce, MBBS, explained at the British Society for Rheumatology annual conference.
“Further research into mortality was one of their top priorities as patients want to know the honest truth about what is going to happen to them,” added Dr. Pearce, of the division of epidemiology and public health at the University of Nottingham (England).
GPA is a rare type of vasculitis that is estimated to occur in around 1,350 people every year in the United Kingdom. Mortality is known to be high, with around 11%-14% of patients dying in the first year of diagnosis, but there are few data on what happens over a longer term.
The aim of the study was therefore to examine patient survival in the long term – what were the mortality rates several years post diagnosis? Did the risk of death remain high throughout this time and did the causes of death change?
“Of course, the important clinical question was, “Can we then improve things?’ ” Dr. Pearce said.
Two U.K. databases – Clinical Practice Research Datalink and Hospital Episode Statistics – were used to identify patients with GPA diagnosed between 1998 and 2014 and match each case to 10 controls based on age, gender, and family practice. Data on the cause and date of any deaths were then obtained from the Office of National Statistics.
Overall, 465 cases of GPA were matched to 4,610 controls. The median age of participants was 61 years and 57% were male. There were 50 cases with more than 10 years of follow-up data available and data on 139 deaths could be analyzed.
A survival analysis showed that there was a significant reduction in cases versus controls, “but it’s not a constant,” Dr. Pearce noted.
“In the time immediately after diagnosis, the risk of death in people with GPA is very high, and over the first 6 months it tails off.” Then the mortalities are very similar, albeit much lower, to those of controls, but with another dip around 8 years.
The number at risk of death in the second year was 310 for GPA vs. 3,543 for controls and 230 vs. 2,622 at 4 years, 138 vs. 1,704 at 6 years, 93 vs. 1,136 at 8 years, and 49 vs. 658 at 10 years.
Looking at the data another way, the hazard ratios for death comparing GPA cases to controls was 24.5 in the first month, 14.6 in months 1-2, 7.5 by 2-3 months, 4.3 at 3-6 months, 1.6 at 6 months to 8 years, and 3.2 at 8-10 years.
Mortality seems to have improved with time. Splitting the cohort into two time periods based on their diagnosis, those diagnosed between 2008 and 2014 had a lower risk of death than did those diagnosed between 1998 and 2007, although it was still more than four times higher than the background population.
The leading cause of death in patients with GPA 5-10 years after diagnosis was cancer (30.3% of cases), but when this was compared against the general population, the risk was no greater (hazard ratio, 1.0).
GPA cases were also 2.9 times more likely than controls to die as a result of an infection, suggesting that this together with CVD could be a target for mortality reduction strategies.
“We can’t get away from the fact that although this is a large study, there are still small numbers of patients because this is rare disease,” Dr. Pearce observed. “We also don’t have detailed clinical information on each patient, so we can’t look for associations or clinical phenotypes at diagnosis, and there are no biomarkers.”
From a clinical perspective, she noted, it is important to remember that deaths in the first year are mainly from active disease and to continue to try to diagnose and treat the condition as early as possible.
Arthritis Research UK funded the trial. Dr. Pearce had nothing to disclose.
SOURCE: Pearce F et al. Rheumatology. 2018;57(Suppl. 3):key075.204.
LIVERPOOL, ENGLAND – Cardiovascular disease was the predominant cause of death of patients with granulomatosis with polyangiitis 1-5 years after a diagnosis in a study by U.K. researchers, suggesting that this could be a target for future intervention.
While active disease was the No. 1 cause of death within the first year of diagnosis in 40% of patients with granulomatosis with polyangiitis (GPA), it was overtaken by cardiovascular disease (CVD) as the main cause of death in 37.5% of patients in the next 4 years from diagnosis.
“The idea for this study came from patients with vasculitis who were polled by Vasculitis UK,” Fiona A. Pearce, MBBS, explained at the British Society for Rheumatology annual conference.
“Further research into mortality was one of their top priorities as patients want to know the honest truth about what is going to happen to them,” added Dr. Pearce, of the division of epidemiology and public health at the University of Nottingham (England).
GPA is a rare type of vasculitis that is estimated to occur in around 1,350 people every year in the United Kingdom. Mortality is known to be high, with around 11%-14% of patients dying in the first year of diagnosis, but there are few data on what happens over a longer term.
The aim of the study was therefore to examine patient survival in the long term – what were the mortality rates several years post diagnosis? Did the risk of death remain high throughout this time and did the causes of death change?
“Of course, the important clinical question was, “Can we then improve things?’ ” Dr. Pearce said.
Two U.K. databases – Clinical Practice Research Datalink and Hospital Episode Statistics – were used to identify patients with GPA diagnosed between 1998 and 2014 and match each case to 10 controls based on age, gender, and family practice. Data on the cause and date of any deaths were then obtained from the Office of National Statistics.
Overall, 465 cases of GPA were matched to 4,610 controls. The median age of participants was 61 years and 57% were male. There were 50 cases with more than 10 years of follow-up data available and data on 139 deaths could be analyzed.
A survival analysis showed that there was a significant reduction in cases versus controls, “but it’s not a constant,” Dr. Pearce noted.
“In the time immediately after diagnosis, the risk of death in people with GPA is very high, and over the first 6 months it tails off.” Then the mortalities are very similar, albeit much lower, to those of controls, but with another dip around 8 years.
The number at risk of death in the second year was 310 for GPA vs. 3,543 for controls and 230 vs. 2,622 at 4 years, 138 vs. 1,704 at 6 years, 93 vs. 1,136 at 8 years, and 49 vs. 658 at 10 years.
Looking at the data another way, the hazard ratios for death comparing GPA cases to controls was 24.5 in the first month, 14.6 in months 1-2, 7.5 by 2-3 months, 4.3 at 3-6 months, 1.6 at 6 months to 8 years, and 3.2 at 8-10 years.
Mortality seems to have improved with time. Splitting the cohort into two time periods based on their diagnosis, those diagnosed between 2008 and 2014 had a lower risk of death than did those diagnosed between 1998 and 2007, although it was still more than four times higher than the background population.
The leading cause of death in patients with GPA 5-10 years after diagnosis was cancer (30.3% of cases), but when this was compared against the general population, the risk was no greater (hazard ratio, 1.0).
GPA cases were also 2.9 times more likely than controls to die as a result of an infection, suggesting that this together with CVD could be a target for mortality reduction strategies.
“We can’t get away from the fact that although this is a large study, there are still small numbers of patients because this is rare disease,” Dr. Pearce observed. “We also don’t have detailed clinical information on each patient, so we can’t look for associations or clinical phenotypes at diagnosis, and there are no biomarkers.”
From a clinical perspective, she noted, it is important to remember that deaths in the first year are mainly from active disease and to continue to try to diagnose and treat the condition as early as possible.
Arthritis Research UK funded the trial. Dr. Pearce had nothing to disclose.
SOURCE: Pearce F et al. Rheumatology. 2018;57(Suppl. 3):key075.204.
LIVERPOOL, ENGLAND – Cardiovascular disease was the predominant cause of death of patients with granulomatosis with polyangiitis 1-5 years after a diagnosis in a study by U.K. researchers, suggesting that this could be a target for future intervention.
While active disease was the No. 1 cause of death within the first year of diagnosis in 40% of patients with granulomatosis with polyangiitis (GPA), it was overtaken by cardiovascular disease (CVD) as the main cause of death in 37.5% of patients in the next 4 years from diagnosis.
“The idea for this study came from patients with vasculitis who were polled by Vasculitis UK,” Fiona A. Pearce, MBBS, explained at the British Society for Rheumatology annual conference.
“Further research into mortality was one of their top priorities as patients want to know the honest truth about what is going to happen to them,” added Dr. Pearce, of the division of epidemiology and public health at the University of Nottingham (England).
GPA is a rare type of vasculitis that is estimated to occur in around 1,350 people every year in the United Kingdom. Mortality is known to be high, with around 11%-14% of patients dying in the first year of diagnosis, but there are few data on what happens over a longer term.
The aim of the study was therefore to examine patient survival in the long term – what were the mortality rates several years post diagnosis? Did the risk of death remain high throughout this time and did the causes of death change?
“Of course, the important clinical question was, “Can we then improve things?’ ” Dr. Pearce said.
Two U.K. databases – Clinical Practice Research Datalink and Hospital Episode Statistics – were used to identify patients with GPA diagnosed between 1998 and 2014 and match each case to 10 controls based on age, gender, and family practice. Data on the cause and date of any deaths were then obtained from the Office of National Statistics.
Overall, 465 cases of GPA were matched to 4,610 controls. The median age of participants was 61 years and 57% were male. There were 50 cases with more than 10 years of follow-up data available and data on 139 deaths could be analyzed.
A survival analysis showed that there was a significant reduction in cases versus controls, “but it’s not a constant,” Dr. Pearce noted.
“In the time immediately after diagnosis, the risk of death in people with GPA is very high, and over the first 6 months it tails off.” Then the mortalities are very similar, albeit much lower, to those of controls, but with another dip around 8 years.
The number at risk of death in the second year was 310 for GPA vs. 3,543 for controls and 230 vs. 2,622 at 4 years, 138 vs. 1,704 at 6 years, 93 vs. 1,136 at 8 years, and 49 vs. 658 at 10 years.
Looking at the data another way, the hazard ratios for death comparing GPA cases to controls was 24.5 in the first month, 14.6 in months 1-2, 7.5 by 2-3 months, 4.3 at 3-6 months, 1.6 at 6 months to 8 years, and 3.2 at 8-10 years.
Mortality seems to have improved with time. Splitting the cohort into two time periods based on their diagnosis, those diagnosed between 2008 and 2014 had a lower risk of death than did those diagnosed between 1998 and 2007, although it was still more than four times higher than the background population.
The leading cause of death in patients with GPA 5-10 years after diagnosis was cancer (30.3% of cases), but when this was compared against the general population, the risk was no greater (hazard ratio, 1.0).
GPA cases were also 2.9 times more likely than controls to die as a result of an infection, suggesting that this together with CVD could be a target for mortality reduction strategies.
“We can’t get away from the fact that although this is a large study, there are still small numbers of patients because this is rare disease,” Dr. Pearce observed. “We also don’t have detailed clinical information on each patient, so we can’t look for associations or clinical phenotypes at diagnosis, and there are no biomarkers.”
From a clinical perspective, she noted, it is important to remember that deaths in the first year are mainly from active disease and to continue to try to diagnose and treat the condition as early as possible.
Arthritis Research UK funded the trial. Dr. Pearce had nothing to disclose.
SOURCE: Pearce F et al. Rheumatology. 2018;57(Suppl. 3):key075.204.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point:
Major finding: The main cause of death changed from active disease (40% of all cases) within the first year to cardiovascular disease at years 1-5 (37.5%).
Study details: Retrospective cohort study of 465 individuals newly diagnosed with granulomatosis with polyangiitis matched to 4,610 controls from the general U.K. primary care population.
Disclosures: Arthritis Research UK funded the trial. Dr. Pearce had nothing to disclose.
Source: Pearce F et al. Rheumatology. 2018;57(Suppl. 3):key075.204.