Eye-opening findings cast spondyloarthritis in new light, expert says

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. – Recent findings have led to eye-opening results in the axial spondyloarthritis (SpA) field, including a surprisingly high number of patients with inflammatory back pain who don’t progress to the disease, healthy people who develop SpA-like details on imaging, and significant gender differences in the efficacy of biologic therapy, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego.

The findings could lead clinicians to see the disease differently and consult with patients in new ways, he said.

Bruce Jancin/Frontline Medical News
Dr. Arthur Kavanaugh
In a Mayo Clinic study published this year (Arthritis Rheumatol. 2018 Feb 22. doi: 10.1002/art.40460), researchers assessed the progress of 124 patients originally seen with what was diagnosed as inflammatory back pain, wondering, what happens to them over time?

Just over 20% of the patients progressed to SpA within 5 years, and about 30% over 15 years. But after 5 years, the condition resolved in over 30% of patients – and after 15 years, it resolved in almost half.

In about 5% of patients, symptoms persisted but the condition remained unidentified.

“A lot of people with inflammatory back pain, it doesn’t continue to be an issue – this goes out a decade and a half,” Dr. Kavanaugh said. “I was surprised with this. I would have guess that over this many years, more people would have developed ankylosing spondylitis, but they don’t.”

He said that clinicians should cite this information in their discussions with patients. They should review their case and evaluate spinal symptoms, but let them know that the condition might not progress and might not be permanent.

 

 


“I would use this information and say, ‘Well you’re having inflammatory back pain, but let’s go review things,’ ” he said. “ ‘If you don’t have the true spondyloarthropathy or ankylosing spondylitis now, there’s a chance that this will go away. It’s almost 50-50, or we still don’t know what it is even if you’re having some symptoms (after 15 years).’ ”

Other important findings underscore the need for a complete clinical picture rather than just findings on imaging for an axial SpA diagnosis, Dr. Kavanaugh said. Researchers examined MRI images of new military recruits who were healthy with no back pain (Rheumatology [Oxford]. 2018 Mar 1;57[3]:508-13). They found that 23% of them at baseline – and 37% after strenuous training – had MRI findings that would qualify as positive for spondyloarthritis by Assessment of Spondyloarthritis international Society criteria. But they wouldn’t meet the definition of disease.



More recent findings showed similar results in imaging of healthy runners and hockey players (Arthritis Rheumatol. 2018 May;70[5]:736-45), with 30%-40% of them having MRI findings that would be considered positive on ASAS, Dr. Kavanaugh said.

“These were just people who were out stressing their joints,” he said. “We were super excited at the start of having MRI because now we can look and evaluate the activity within a joint. But I think, like everything, we have to take it with a little bit of caution. Just in and of itself, without the clinical picture, it does not diagnose axial spondyloarthropathy.”

 

 


In another recent study, women with axial SpA were found to have significantly lower responses over time than men with axial SpA (J Rheumatol. 2018 Feb;45[2]:195-201). Dr. Kavanaugh said that there might be some selection bias because of the higher male prevalence of disease but said the findings were noteworthy, especially in light of findings in animal models suggesting gender differences in disease expression and response to treatment.

“I think this is fascinating,” he said. “I think there’s a lot more to come for this.”

Dr. Kavanaugh reported financial relationships with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Genentech, Novartis, Pfizer, and other companies.

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. – Recent findings have led to eye-opening results in the axial spondyloarthritis (SpA) field, including a surprisingly high number of patients with inflammatory back pain who don’t progress to the disease, healthy people who develop SpA-like details on imaging, and significant gender differences in the efficacy of biologic therapy, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego.

The findings could lead clinicians to see the disease differently and consult with patients in new ways, he said.

Bruce Jancin/Frontline Medical News
Dr. Arthur Kavanaugh
In a Mayo Clinic study published this year (Arthritis Rheumatol. 2018 Feb 22. doi: 10.1002/art.40460), researchers assessed the progress of 124 patients originally seen with what was diagnosed as inflammatory back pain, wondering, what happens to them over time?

Just over 20% of the patients progressed to SpA within 5 years, and about 30% over 15 years. But after 5 years, the condition resolved in over 30% of patients – and after 15 years, it resolved in almost half.

In about 5% of patients, symptoms persisted but the condition remained unidentified.

“A lot of people with inflammatory back pain, it doesn’t continue to be an issue – this goes out a decade and a half,” Dr. Kavanaugh said. “I was surprised with this. I would have guess that over this many years, more people would have developed ankylosing spondylitis, but they don’t.”

He said that clinicians should cite this information in their discussions with patients. They should review their case and evaluate spinal symptoms, but let them know that the condition might not progress and might not be permanent.

 

 


“I would use this information and say, ‘Well you’re having inflammatory back pain, but let’s go review things,’ ” he said. “ ‘If you don’t have the true spondyloarthropathy or ankylosing spondylitis now, there’s a chance that this will go away. It’s almost 50-50, or we still don’t know what it is even if you’re having some symptoms (after 15 years).’ ”

Other important findings underscore the need for a complete clinical picture rather than just findings on imaging for an axial SpA diagnosis, Dr. Kavanaugh said. Researchers examined MRI images of new military recruits who were healthy with no back pain (Rheumatology [Oxford]. 2018 Mar 1;57[3]:508-13). They found that 23% of them at baseline – and 37% after strenuous training – had MRI findings that would qualify as positive for spondyloarthritis by Assessment of Spondyloarthritis international Society criteria. But they wouldn’t meet the definition of disease.



More recent findings showed similar results in imaging of healthy runners and hockey players (Arthritis Rheumatol. 2018 May;70[5]:736-45), with 30%-40% of them having MRI findings that would be considered positive on ASAS, Dr. Kavanaugh said.

“These were just people who were out stressing their joints,” he said. “We were super excited at the start of having MRI because now we can look and evaluate the activity within a joint. But I think, like everything, we have to take it with a little bit of caution. Just in and of itself, without the clinical picture, it does not diagnose axial spondyloarthropathy.”

 

 


In another recent study, women with axial SpA were found to have significantly lower responses over time than men with axial SpA (J Rheumatol. 2018 Feb;45[2]:195-201). Dr. Kavanaugh said that there might be some selection bias because of the higher male prevalence of disease but said the findings were noteworthy, especially in light of findings in animal models suggesting gender differences in disease expression and response to treatment.

“I think this is fascinating,” he said. “I think there’s a lot more to come for this.”

Dr. Kavanaugh reported financial relationships with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Genentech, Novartis, Pfizer, and other companies.

 

. – Recent findings have led to eye-opening results in the axial spondyloarthritis (SpA) field, including a surprisingly high number of patients with inflammatory back pain who don’t progress to the disease, healthy people who develop SpA-like details on imaging, and significant gender differences in the efficacy of biologic therapy, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego.

The findings could lead clinicians to see the disease differently and consult with patients in new ways, he said.

Bruce Jancin/Frontline Medical News
Dr. Arthur Kavanaugh
In a Mayo Clinic study published this year (Arthritis Rheumatol. 2018 Feb 22. doi: 10.1002/art.40460), researchers assessed the progress of 124 patients originally seen with what was diagnosed as inflammatory back pain, wondering, what happens to them over time?

Just over 20% of the patients progressed to SpA within 5 years, and about 30% over 15 years. But after 5 years, the condition resolved in over 30% of patients – and after 15 years, it resolved in almost half.

In about 5% of patients, symptoms persisted but the condition remained unidentified.

“A lot of people with inflammatory back pain, it doesn’t continue to be an issue – this goes out a decade and a half,” Dr. Kavanaugh said. “I was surprised with this. I would have guess that over this many years, more people would have developed ankylosing spondylitis, but they don’t.”

He said that clinicians should cite this information in their discussions with patients. They should review their case and evaluate spinal symptoms, but let them know that the condition might not progress and might not be permanent.

 

 


“I would use this information and say, ‘Well you’re having inflammatory back pain, but let’s go review things,’ ” he said. “ ‘If you don’t have the true spondyloarthropathy or ankylosing spondylitis now, there’s a chance that this will go away. It’s almost 50-50, or we still don’t know what it is even if you’re having some symptoms (after 15 years).’ ”

Other important findings underscore the need for a complete clinical picture rather than just findings on imaging for an axial SpA diagnosis, Dr. Kavanaugh said. Researchers examined MRI images of new military recruits who were healthy with no back pain (Rheumatology [Oxford]. 2018 Mar 1;57[3]:508-13). They found that 23% of them at baseline – and 37% after strenuous training – had MRI findings that would qualify as positive for spondyloarthritis by Assessment of Spondyloarthritis international Society criteria. But they wouldn’t meet the definition of disease.



More recent findings showed similar results in imaging of healthy runners and hockey players (Arthritis Rheumatol. 2018 May;70[5]:736-45), with 30%-40% of them having MRI findings that would be considered positive on ASAS, Dr. Kavanaugh said.

“These were just people who were out stressing their joints,” he said. “We were super excited at the start of having MRI because now we can look and evaluate the activity within a joint. But I think, like everything, we have to take it with a little bit of caution. Just in and of itself, without the clinical picture, it does not diagnose axial spondyloarthropathy.”

 

 


In another recent study, women with axial SpA were found to have significantly lower responses over time than men with axial SpA (J Rheumatol. 2018 Feb;45[2]:195-201). Dr. Kavanaugh said that there might be some selection bias because of the higher male prevalence of disease but said the findings were noteworthy, especially in light of findings in animal models suggesting gender differences in disease expression and response to treatment.

“I think this is fascinating,” he said. “I think there’s a lot more to come for this.”

Dr. Kavanaugh reported financial relationships with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Genentech, Novartis, Pfizer, and other companies.

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Caution crucial for stem cell transplant in scleroderma, despite potential interest

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Mon, 01/14/2019 - 10:24

 

SANDESTIN, FLA. – An expert called for restraint with the use of stem cell transplantation in scleroderma at the annual Congress of Clinical Rheumatology, emphasizing that the early mortality risk shows that the patient group that should be considered for the treatment is very narrow.

Results published earlier this year found a long-term benefit for myeloablative autologous stem cell transplantation, compared with cyclophosphamide, and were highly encouraging – but only in patients with severe disease (N Engl J Med. 2018;378:35-47). This might prompt patients to express interest in the treatment, many of whom are not suitable, said Janet Pope, MD, chair of rheumatology at St. Joseph’s Health Care in London, Ont.

Dr. Janet Pope
“Your patients with scleroderma are savvy. They will be on the Internet,” she said. “They know someone who knows someone who told them about it. Most of our patients are not eligible.”

Because of mortality seen in the first year in the stem cell transplant group, the benefit over cyclophosphamide was seen only in subsequent years, Dr. Pope stressed.

Consideration of the approach is only appropriate for patients with early diffuse scleroderma who have a 50% mortality risk over 5 years, Dr. Pope said. Patients in the SCOT trial had a modified Rodnan Skin Score (mRSS) of 30, with an average forced vital capacity of 74%, and 73 of the 75 patients in the trial had lung involvement. Essentially, Dr. Pope said, these are patients with some organ involvement that could be lethal, but not such severe organ involvement that it requires a transplant.

“These are our sick patients,” she said.

The results published this year are even more definitive, Dr. Pope said, considering that they largely meshed with results out of Europe, published in 2014, that showed that the stem cell transplant benefit was not seen after the first year because of early mortality (JAMA. 2014 Jun 25;311[24]:2490-8). In that trial, a 10% mortality risk was seen in the first year in the transplant group, and then a benefit to transplant in the long term over cyclophosphamide.

 

 


“These are very complementary positive trials,” Dr. Pope said. “We don’t want to kill 10% of our patients who don’t have perceived high chance of mortality in the next 5 years. ... These patients are highly selected, but I think it gives our patients hope and, for some of my patients, this will be a treatment for them.”

The long-term efficacy is also encouraging in that new but less potent treatments might yield good long-term results without the early deaths, she said. “It gives an idea and hope, and it helps us to understand that maybe with immune modulation, without the nuclear blast of stem cell transplant, maybe we can do better for our patients.”

Dr. Pope reported relevant financial relationships with Actelion, Bayer, Merck, Bristol-Myers Squibb, and Roche.
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SANDESTIN, FLA. – An expert called for restraint with the use of stem cell transplantation in scleroderma at the annual Congress of Clinical Rheumatology, emphasizing that the early mortality risk shows that the patient group that should be considered for the treatment is very narrow.

Results published earlier this year found a long-term benefit for myeloablative autologous stem cell transplantation, compared with cyclophosphamide, and were highly encouraging – but only in patients with severe disease (N Engl J Med. 2018;378:35-47). This might prompt patients to express interest in the treatment, many of whom are not suitable, said Janet Pope, MD, chair of rheumatology at St. Joseph’s Health Care in London, Ont.

Dr. Janet Pope
“Your patients with scleroderma are savvy. They will be on the Internet,” she said. “They know someone who knows someone who told them about it. Most of our patients are not eligible.”

Because of mortality seen in the first year in the stem cell transplant group, the benefit over cyclophosphamide was seen only in subsequent years, Dr. Pope stressed.

Consideration of the approach is only appropriate for patients with early diffuse scleroderma who have a 50% mortality risk over 5 years, Dr. Pope said. Patients in the SCOT trial had a modified Rodnan Skin Score (mRSS) of 30, with an average forced vital capacity of 74%, and 73 of the 75 patients in the trial had lung involvement. Essentially, Dr. Pope said, these are patients with some organ involvement that could be lethal, but not such severe organ involvement that it requires a transplant.

“These are our sick patients,” she said.

The results published this year are even more definitive, Dr. Pope said, considering that they largely meshed with results out of Europe, published in 2014, that showed that the stem cell transplant benefit was not seen after the first year because of early mortality (JAMA. 2014 Jun 25;311[24]:2490-8). In that trial, a 10% mortality risk was seen in the first year in the transplant group, and then a benefit to transplant in the long term over cyclophosphamide.

 

 


“These are very complementary positive trials,” Dr. Pope said. “We don’t want to kill 10% of our patients who don’t have perceived high chance of mortality in the next 5 years. ... These patients are highly selected, but I think it gives our patients hope and, for some of my patients, this will be a treatment for them.”

The long-term efficacy is also encouraging in that new but less potent treatments might yield good long-term results without the early deaths, she said. “It gives an idea and hope, and it helps us to understand that maybe with immune modulation, without the nuclear blast of stem cell transplant, maybe we can do better for our patients.”

Dr. Pope reported relevant financial relationships with Actelion, Bayer, Merck, Bristol-Myers Squibb, and Roche.

 

SANDESTIN, FLA. – An expert called for restraint with the use of stem cell transplantation in scleroderma at the annual Congress of Clinical Rheumatology, emphasizing that the early mortality risk shows that the patient group that should be considered for the treatment is very narrow.

Results published earlier this year found a long-term benefit for myeloablative autologous stem cell transplantation, compared with cyclophosphamide, and were highly encouraging – but only in patients with severe disease (N Engl J Med. 2018;378:35-47). This might prompt patients to express interest in the treatment, many of whom are not suitable, said Janet Pope, MD, chair of rheumatology at St. Joseph’s Health Care in London, Ont.

Dr. Janet Pope
“Your patients with scleroderma are savvy. They will be on the Internet,” she said. “They know someone who knows someone who told them about it. Most of our patients are not eligible.”

Because of mortality seen in the first year in the stem cell transplant group, the benefit over cyclophosphamide was seen only in subsequent years, Dr. Pope stressed.

Consideration of the approach is only appropriate for patients with early diffuse scleroderma who have a 50% mortality risk over 5 years, Dr. Pope said. Patients in the SCOT trial had a modified Rodnan Skin Score (mRSS) of 30, with an average forced vital capacity of 74%, and 73 of the 75 patients in the trial had lung involvement. Essentially, Dr. Pope said, these are patients with some organ involvement that could be lethal, but not such severe organ involvement that it requires a transplant.

“These are our sick patients,” she said.

The results published this year are even more definitive, Dr. Pope said, considering that they largely meshed with results out of Europe, published in 2014, that showed that the stem cell transplant benefit was not seen after the first year because of early mortality (JAMA. 2014 Jun 25;311[24]:2490-8). In that trial, a 10% mortality risk was seen in the first year in the transplant group, and then a benefit to transplant in the long term over cyclophosphamide.

 

 


“These are very complementary positive trials,” Dr. Pope said. “We don’t want to kill 10% of our patients who don’t have perceived high chance of mortality in the next 5 years. ... These patients are highly selected, but I think it gives our patients hope and, for some of my patients, this will be a treatment for them.”

The long-term efficacy is also encouraging in that new but less potent treatments might yield good long-term results without the early deaths, she said. “It gives an idea and hope, and it helps us to understand that maybe with immune modulation, without the nuclear blast of stem cell transplant, maybe we can do better for our patients.”

Dr. Pope reported relevant financial relationships with Actelion, Bayer, Merck, Bristol-Myers Squibb, and Roche.
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New agents may bring hope for SLE patients

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– 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.

 

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– 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.

 

– 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.

 

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Newer IgG4 testing proving effective in assessing patients

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Thu, 12/06/2018 - 11:59

 

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.

Dr. Arezou Khosroshahi
She said she once had a 54-year-old woman as a patient who had enlarged bilateral lacrimal and salivary glands, with lymphadenopathy. She suspected IgG4 levels would be elevated, but, surprisingly, they weren’t.

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.

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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.

Dr. Arezou Khosroshahi
She said she once had a 54-year-old woman as a patient who had enlarged bilateral lacrimal and salivary glands, with lymphadenopathy. She suspected IgG4 levels would be elevated, but, surprisingly, they weren’t.

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.

Dr. Arezou Khosroshahi
She said she once had a 54-year-old woman as a patient who had enlarged bilateral lacrimal and salivary glands, with lymphadenopathy. She suspected IgG4 levels would be elevated, but, surprisingly, they weren’t.

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.

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Conservative early approach likely best, RA expert says

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Sat, 12/08/2018 - 15:04

 

SANDESTIN, FLA. – A conservative approach to early rheumatoid arthritis treatment has carried the day in the practice of Gerd R. Burmester, MD.

In a talk at the annual Congress of Clinical Rheumatology, Dr. Burmester said that, although there is room to argue for a more aggressive approach, with more intense treatment early, a less aggressive philosophy has worked well in his clinic.

Dr. Gerd R. Burmester


Dr. Burmester, director of rheumatology and clinical immunology at Charite-University in Berlin and a past president of the European League Against Rheumatism (EULAR), said he drew inspiration from the results of the 2015 study CARE-RA, in which patients were treated with initial therapy of methotrexate plus sulfasalazine and a fairly high dose of 60 mg of prednisolone; methotrexate plus leflunomide plus 30 mg of prednisolone; or just methotrexate plus 30 mg of prednisolone that is quickly tapered down (Ann Rheum Dis. 2015 Jan;74[1]:27-34).

“Everyone would say, ‘Okay, this is quite easy – the more intensive drug regimen should give you better results,’ ” Dr. Burmester said. “But if you look at the data, there’s no difference.” And after just 8 weeks, the patients’ corticosteroid dose was down to 5 mg.

This, he said, “has changed my daily typical practice, quite a bit.”

“I start with, usually, 15 mg of methotrexate subcutaneously,” because of better efficacy and less liver toxicity than oral administration, he said, or an oral dose if a patient resists the subcutaneous administration or there is another reason to avoid it. “And I add 30 mg of prednisone and taper it down – 30, 20, 12.5 mg, and then down to 5 and eventually discontinued altogether.”

“This is an interesting scheme,” he said. “And this is exactly what I do with my patients.”

 

 


His approach might be worth noting not only for his leadership roles, but because of his fastidious approach to being a clinician – he said he still, personally, takes every patient’s 28-joint Disease Activity Score and Simple Disease Activity Index at every visit.

In a recent paper, he argued, along with prominent Canadian rheumatologist Janet Pope, both sides of the debate, for and against more aggressive treatment – methotrexate combined with conventional synthetic or biologic DMARDs – very early in the disease course (Lancet. 2017 Jun 10;389[10086]:2338-48).

“If you use a combination treatment with a biologic right away, what might be the advantages?” he said. “More patients would achieve rapid remission. It might result in long-term benefits, less joint damage, higher chance of reducing therapy in the future.”

On the other hand, he said, there are disadvantages.
 

 


“This is, of course, more expensive, if you use a biologic up front in early RA,” he said. “Not all patients of course need it, and some have also side effects.” He added that little time is lost if a treat-to-target principle is followed. Plus, patients tend to be more accepting of monotherapy than combination therapy at the start of treatment, and combination therapy might require more time spent in the clinic.

Data from German databases, dating back to 1997, show that far more patients are reaching remission today after several years of treatment (Z Rheumatol. 2017 Feb;76[1]:50-7). But, he added, “It’s not yet perfect. ... We still have quite a few patients who are in moderate disease activity” despite the availability of so many treatment options.

“There’s still, of course, a huge unmet need in this devastating disease if you don’t treat it correctly.”

Dr. Burmester reports receiving clinical trial support and/or honoraria for lectures and consulting from AbbVie, Bristol-Myers Squibb, Lilly, Roche, MedImmune, Merck Sharpe & Dohme, Pfizer, Sanofi, and UCB.
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SANDESTIN, FLA. – A conservative approach to early rheumatoid arthritis treatment has carried the day in the practice of Gerd R. Burmester, MD.

In a talk at the annual Congress of Clinical Rheumatology, Dr. Burmester said that, although there is room to argue for a more aggressive approach, with more intense treatment early, a less aggressive philosophy has worked well in his clinic.

Dr. Gerd R. Burmester


Dr. Burmester, director of rheumatology and clinical immunology at Charite-University in Berlin and a past president of the European League Against Rheumatism (EULAR), said he drew inspiration from the results of the 2015 study CARE-RA, in which patients were treated with initial therapy of methotrexate plus sulfasalazine and a fairly high dose of 60 mg of prednisolone; methotrexate plus leflunomide plus 30 mg of prednisolone; or just methotrexate plus 30 mg of prednisolone that is quickly tapered down (Ann Rheum Dis. 2015 Jan;74[1]:27-34).

“Everyone would say, ‘Okay, this is quite easy – the more intensive drug regimen should give you better results,’ ” Dr. Burmester said. “But if you look at the data, there’s no difference.” And after just 8 weeks, the patients’ corticosteroid dose was down to 5 mg.

This, he said, “has changed my daily typical practice, quite a bit.”

“I start with, usually, 15 mg of methotrexate subcutaneously,” because of better efficacy and less liver toxicity than oral administration, he said, or an oral dose if a patient resists the subcutaneous administration or there is another reason to avoid it. “And I add 30 mg of prednisone and taper it down – 30, 20, 12.5 mg, and then down to 5 and eventually discontinued altogether.”

“This is an interesting scheme,” he said. “And this is exactly what I do with my patients.”

 

 


His approach might be worth noting not only for his leadership roles, but because of his fastidious approach to being a clinician – he said he still, personally, takes every patient’s 28-joint Disease Activity Score and Simple Disease Activity Index at every visit.

In a recent paper, he argued, along with prominent Canadian rheumatologist Janet Pope, both sides of the debate, for and against more aggressive treatment – methotrexate combined with conventional synthetic or biologic DMARDs – very early in the disease course (Lancet. 2017 Jun 10;389[10086]:2338-48).

“If you use a combination treatment with a biologic right away, what might be the advantages?” he said. “More patients would achieve rapid remission. It might result in long-term benefits, less joint damage, higher chance of reducing therapy in the future.”

On the other hand, he said, there are disadvantages.
 

 


“This is, of course, more expensive, if you use a biologic up front in early RA,” he said. “Not all patients of course need it, and some have also side effects.” He added that little time is lost if a treat-to-target principle is followed. Plus, patients tend to be more accepting of monotherapy than combination therapy at the start of treatment, and combination therapy might require more time spent in the clinic.

Data from German databases, dating back to 1997, show that far more patients are reaching remission today after several years of treatment (Z Rheumatol. 2017 Feb;76[1]:50-7). But, he added, “It’s not yet perfect. ... We still have quite a few patients who are in moderate disease activity” despite the availability of so many treatment options.

“There’s still, of course, a huge unmet need in this devastating disease if you don’t treat it correctly.”

Dr. Burmester reports receiving clinical trial support and/or honoraria for lectures and consulting from AbbVie, Bristol-Myers Squibb, Lilly, Roche, MedImmune, Merck Sharpe & Dohme, Pfizer, Sanofi, and UCB.

 

SANDESTIN, FLA. – A conservative approach to early rheumatoid arthritis treatment has carried the day in the practice of Gerd R. Burmester, MD.

In a talk at the annual Congress of Clinical Rheumatology, Dr. Burmester said that, although there is room to argue for a more aggressive approach, with more intense treatment early, a less aggressive philosophy has worked well in his clinic.

Dr. Gerd R. Burmester


Dr. Burmester, director of rheumatology and clinical immunology at Charite-University in Berlin and a past president of the European League Against Rheumatism (EULAR), said he drew inspiration from the results of the 2015 study CARE-RA, in which patients were treated with initial therapy of methotrexate plus sulfasalazine and a fairly high dose of 60 mg of prednisolone; methotrexate plus leflunomide plus 30 mg of prednisolone; or just methotrexate plus 30 mg of prednisolone that is quickly tapered down (Ann Rheum Dis. 2015 Jan;74[1]:27-34).

“Everyone would say, ‘Okay, this is quite easy – the more intensive drug regimen should give you better results,’ ” Dr. Burmester said. “But if you look at the data, there’s no difference.” And after just 8 weeks, the patients’ corticosteroid dose was down to 5 mg.

This, he said, “has changed my daily typical practice, quite a bit.”

“I start with, usually, 15 mg of methotrexate subcutaneously,” because of better efficacy and less liver toxicity than oral administration, he said, or an oral dose if a patient resists the subcutaneous administration or there is another reason to avoid it. “And I add 30 mg of prednisone and taper it down – 30, 20, 12.5 mg, and then down to 5 and eventually discontinued altogether.”

“This is an interesting scheme,” he said. “And this is exactly what I do with my patients.”

 

 


His approach might be worth noting not only for his leadership roles, but because of his fastidious approach to being a clinician – he said he still, personally, takes every patient’s 28-joint Disease Activity Score and Simple Disease Activity Index at every visit.

In a recent paper, he argued, along with prominent Canadian rheumatologist Janet Pope, both sides of the debate, for and against more aggressive treatment – methotrexate combined with conventional synthetic or biologic DMARDs – very early in the disease course (Lancet. 2017 Jun 10;389[10086]:2338-48).

“If you use a combination treatment with a biologic right away, what might be the advantages?” he said. “More patients would achieve rapid remission. It might result in long-term benefits, less joint damage, higher chance of reducing therapy in the future.”

On the other hand, he said, there are disadvantages.
 

 


“This is, of course, more expensive, if you use a biologic up front in early RA,” he said. “Not all patients of course need it, and some have also side effects.” He added that little time is lost if a treat-to-target principle is followed. Plus, patients tend to be more accepting of monotherapy than combination therapy at the start of treatment, and combination therapy might require more time spent in the clinic.

Data from German databases, dating back to 1997, show that far more patients are reaching remission today after several years of treatment (Z Rheumatol. 2017 Feb;76[1]:50-7). But, he added, “It’s not yet perfect. ... We still have quite a few patients who are in moderate disease activity” despite the availability of so many treatment options.

“There’s still, of course, a huge unmet need in this devastating disease if you don’t treat it correctly.”

Dr. Burmester reports receiving clinical trial support and/or honoraria for lectures and consulting from AbbVie, Bristol-Myers Squibb, Lilly, Roche, MedImmune, Merck Sharpe & Dohme, Pfizer, Sanofi, and UCB.
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VIDEO: Calming microglia might control fibromyalgia

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Fri, 01/18/2019 - 17:40

– 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, treating fibromyalgia with dextronaltrexone would potentially leave open the possibility of coadministration with an opioid, 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.
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– 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, treating fibromyalgia with dextronaltrexone would potentially leave open the possibility of coadministration with an opioid, 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.

– 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, treating fibromyalgia with dextronaltrexone would potentially leave open the possibility of coadministration with an opioid, 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.
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VIDEO: Second wave of psoriatic arthritis therapies

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Tue, 02/07/2023 - 16:54

SANDESTIN, FLA. – An array of potential new options for psoriatic arthritis offers new targeted options and poses challenges for how to use the drugs, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, said in a video interview at the annual Congress of Clinical Rheumatology.

“We’re seeing a second wave – a second wave driven by the additional ways that we have to target aspects of the immune system relevant to psoriatic arthritis,” he said.

First used to treat rheumatoid arthritis, monoclonal antibodies to interleukin targets, including IL12 and IL23 (ustekinumab) and IL17 (secukinumab and ixekizumab), have become established psoriatic arthritis therapies. Additionally, the Janus kinase (JAK) inhibitor tofacitinib has become an option.

Other options in the pipeline include the JAK inhibitor baricitinib; the anti-IL23 monoclonal antibodies guselkumab, risankizumab, and tildrakizumab; and even more anti-IL17 therapies, including brodalumab and bimekizumab .

“Now we have the synergy of having novel therapeutic approaches to maybe address some of the different domains of disease,” he said. Despite efforts to develop better biomarkers, it’s hard to predict how an individual patient will respond to a specific therapy. The longer the menu of therapeutic options, the better it is for patients.

As methotrexate remains a go-to treatment for many patients, new data from the SEAM trial assessing etanercept and methotrexate will address the question of whether the conventional drug and tumor necrosis factor inhibitors create therapeutic synergy in patients with psoriatic arthritis.

Dr. Kavanaugh discussed the implications of the trial’s findings, which are expected to go public this summer.

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SANDESTIN, FLA. – An array of potential new options for psoriatic arthritis offers new targeted options and poses challenges for how to use the drugs, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, said in a video interview at the annual Congress of Clinical Rheumatology.

“We’re seeing a second wave – a second wave driven by the additional ways that we have to target aspects of the immune system relevant to psoriatic arthritis,” he said.

First used to treat rheumatoid arthritis, monoclonal antibodies to interleukin targets, including IL12 and IL23 (ustekinumab) and IL17 (secukinumab and ixekizumab), have become established psoriatic arthritis therapies. Additionally, the Janus kinase (JAK) inhibitor tofacitinib has become an option.

Other options in the pipeline include the JAK inhibitor baricitinib; the anti-IL23 monoclonal antibodies guselkumab, risankizumab, and tildrakizumab; and even more anti-IL17 therapies, including brodalumab and bimekizumab .

“Now we have the synergy of having novel therapeutic approaches to maybe address some of the different domains of disease,” he said. Despite efforts to develop better biomarkers, it’s hard to predict how an individual patient will respond to a specific therapy. The longer the menu of therapeutic options, the better it is for patients.

As methotrexate remains a go-to treatment for many patients, new data from the SEAM trial assessing etanercept and methotrexate will address the question of whether the conventional drug and tumor necrosis factor inhibitors create therapeutic synergy in patients with psoriatic arthritis.

Dr. Kavanaugh discussed the implications of the trial’s findings, which are expected to go public this summer.

SANDESTIN, FLA. – An array of potential new options for psoriatic arthritis offers new targeted options and poses challenges for how to use the drugs, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, said in a video interview at the annual Congress of Clinical Rheumatology.

“We’re seeing a second wave – a second wave driven by the additional ways that we have to target aspects of the immune system relevant to psoriatic arthritis,” he said.

First used to treat rheumatoid arthritis, monoclonal antibodies to interleukin targets, including IL12 and IL23 (ustekinumab) and IL17 (secukinumab and ixekizumab), have become established psoriatic arthritis therapies. Additionally, the Janus kinase (JAK) inhibitor tofacitinib has become an option.

Other options in the pipeline include the JAK inhibitor baricitinib; the anti-IL23 monoclonal antibodies guselkumab, risankizumab, and tildrakizumab; and even more anti-IL17 therapies, including brodalumab and bimekizumab .

“Now we have the synergy of having novel therapeutic approaches to maybe address some of the different domains of disease,” he said. Despite efforts to develop better biomarkers, it’s hard to predict how an individual patient will respond to a specific therapy. The longer the menu of therapeutic options, the better it is for patients.

As methotrexate remains a go-to treatment for many patients, new data from the SEAM trial assessing etanercept and methotrexate will address the question of whether the conventional drug and tumor necrosis factor inhibitors create therapeutic synergy in patients with psoriatic arthritis.

Dr. Kavanaugh discussed the implications of the trial’s findings, which are expected to go public this summer.

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VIDEO: Pills alone not the answer for pain management

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Thu, 01/21/2021 - 11:28

SANDESTIN, FLA. – More than ever, clinicians need to rely on a multimodal approach to pain management, Katherine Galluzzi, DO, said at the annual Congress of Clinical Rheumatology.

In the era of opioid addiction – in which she said physicians have sometimes been unfairly vilified – pharmaceutical options are limited not only by the threat of abuse but also by governmental regulation, explained Dr. Galluzzi, chair of geriatrics at the Philadelphia College of Osteopathic Medicine.

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SANDESTIN, FLA. – More than ever, clinicians need to rely on a multimodal approach to pain management, Katherine Galluzzi, DO, said at the annual Congress of Clinical Rheumatology.

In the era of opioid addiction – in which she said physicians have sometimes been unfairly vilified – pharmaceutical options are limited not only by the threat of abuse but also by governmental regulation, explained Dr. Galluzzi, chair of geriatrics at the Philadelphia College of Osteopathic Medicine.

SANDESTIN, FLA. – More than ever, clinicians need to rely on a multimodal approach to pain management, Katherine Galluzzi, DO, said at the annual Congress of Clinical Rheumatology.

In the era of opioid addiction – in which she said physicians have sometimes been unfairly vilified – pharmaceutical options are limited not only by the threat of abuse but also by governmental regulation, explained Dr. Galluzzi, chair of geriatrics at the Philadelphia College of Osteopathic Medicine.

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VIDEO: Characteristic flora define intestinal microbiome in scleroderma

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Fri, 01/18/2019 - 17:40

– 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.
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– 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.

– 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.
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VIDEO: Skin exam crucial in rheumatic diseases, expert says

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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.

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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.

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