Javier Bolaños-Meade, MD

SALT LAKE CITY—Cure of severe hemoglobinopathies is now possible for most patients, according to a speaker at the 2018 BMT Tandem Meetings.

Results of a small study suggest that nonmyeloablative haploidentical bone marrow transplant (minihaplo-BMT), when used with 400 cGy total body irradiation and post-transplant cyclophosphamide, can cure sickle cell disease (SCD) and beta-thalassemia while conferring limited toxicity.

“This is our second study showing that you can certainly get rid of these conditions using haploidentical donors and, also, that you can cure these conditions with a nonmyeloablative regimen,” said Javier Bolaños-Meade, MD, of Johns Hopkins University in Baltimore, Maryland.

“What we saw [in the current study] is that increasing the total body irradiation from 200 cGy to 400 cGy can overcome the very high rate of graft failure we observed in our prior study.”

However, the results also suggest that major ABO incompatible donors should be avoided.

Dr Bolaños-Meade presented these findings as a late-breaking abstract (LBA3) at this year’s BMT Tandem Meetings.

He began the presentation by pointing out that allogeneic BMT is the only potential cure for SCD and beta-thalassemia. Unfortunately, most of these patients have been excluded from transplant due to a lack of matched donors, concerns over graft-vs-host disease (GVHD), and/or compromised end organ function precluding them from myeloablative conditioning.

With a prior study, Dr Bolaños-Meade and his colleagues found that minihaplo-BMT with post-transplant cyclophosphamide expanded the donor pool and was well tolerated in patients with SCD. However, the rate of secondary graft failure was high, at 43%.

“We hypothesized that increasing the amount of radiation that was given to these patients, making the regimen absolutely more intensive, will help us to overcome this rate of graft failure and retain the tolerability of the regimen,” Dr Bolaños-Meade said.

He and his colleagues tested this theory in 12 patients with SCD and 5 with beta-thalassemia.

The SCD patients had a median age of 26 (range, 6-31), and most (n=8) were female. Ten were African-American, and 2 were of Arab descent.

All SCD patients had at least 2 hospital admissions in the last 2 years, 5 had osteonecrosis, 3 were transfusion-dependent, 2 had a history of acute chest syndrome, and 1 patient had changes in brain magnetic resonance imaging.

The thalassemia patients had a median age of 7 (range, 6-16). Four were female, and all 5 were of Arab descent. All patients were transfusion-dependent from infancy.

Treatment

All patients received antithymocyte globulin (rabbit) at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, fludarabine at 30 mg/m² on days -6 to -2, cyclophosphamide at 14.5 mg/kg on days -6 and -5, and total body irradiation at 400 cGy on day -1.

Patients received unmanipulated bone marrow that was collected and infused on day 0. Donors included 1 aunt, 4 brothers, 3 sisters, 5 mothers, and 4 fathers. There were 2 major ABO incompatible pairs, 5 minor ABO incompatible pairs, and 10 ABO compatible pairs.

For GVHD prophylaxis, patients received 50 mg/kg/day of cyclophosphamide on days 3 and 4, sirolimus (levels of 5-10 ng/dl) from days 5 to 365, and mycophenolate mofetil at 1 g every 8 hours from days 5 to 35.

Efficacy

All 17 patients are still alive at a median follow-up of 15 months (range, 3-34).

“Of all the patients transplanted, we only observed 1 graft failure,” Dr Bolaños-Meade said. “This is in sharp contrast to the 40% graft failure in our prior study.”

Thirteen patients achieved full donor chimerism, and 3 had mixed chimerism.

Four of the 5 beta-thalassemia patients achieved full donor chimerism, and 1 had mixed chimerism. All 5 patients became transfusion-independent.

Eleven of the 12 SCD patients engrafted, and 9 achieved full donor chimerism.

All but one of the engrafted SCD patients became transfusion-independent. The exception was a mixed chimeric patient who had a major ABO mismatched donor. The patient remains transfusion-dependent more than 30 months after BMT.

“This is the main problem we have seen in all our sickle cell and hemoglobinopathy experiences,” Dr Bolaños-Meade said. “If you have a major ABO incompatibility, and there’s mixed chimerism, you’re asking for trouble.”

Toxicity

All SCD patients had sickle cell crises after antithymocyte globulin. Other toxicities included sirolimus-induced diabetes in 1 patient, worsening of Meniere’s disease in 1 patient, and BK cystitis in 1 patient.

Two patients developed grade 2 acute GVHD, and 1 developed grade 3 acute GVHD. Three patients had chronic GVHD, 2 mild and 1 moderate.

However, all cases of GVHD resolved. And, of the 8 engrafted patients with more than 1 year of follow-up, 6 are off systemic immunosuppression.

Javier Bolaños-Meade, MD

SALT LAKE CITY—Cure of severe hemoglobinopathies is now possible for most patients, according to a speaker at the 2018 BMT Tandem Meetings.

Results of a small study suggest that nonmyeloablative haploidentical bone marrow transplant (minihaplo-BMT), when used with 400 cGy total body irradiation and post-transplant cyclophosphamide, can cure sickle cell disease (SCD) and beta-thalassemia while conferring limited toxicity.

“This is our second study showing that you can certainly get rid of these conditions using haploidentical donors and, also, that you can cure these conditions with a nonmyeloablative regimen,” said Javier Bolaños-Meade, MD, of Johns Hopkins University in Baltimore, Maryland.

“What we saw [in the current study] is that increasing the total body irradiation from 200 cGy to 400 cGy can overcome the very high rate of graft failure we observed in our prior study.”

However, the results also suggest that major ABO incompatible donors should be avoided.

Dr Bolaños-Meade presented these findings as a late-breaking abstract (LBA3) at this year’s BMT Tandem Meetings.

He began the presentation by pointing out that allogeneic BMT is the only potential cure for SCD and beta-thalassemia. Unfortunately, most of these patients have been excluded from transplant due to a lack of matched donors, concerns over graft-vs-host disease (GVHD), and/or compromised end organ function precluding them from myeloablative conditioning.

With a prior study, Dr Bolaños-Meade and his colleagues found that minihaplo-BMT with post-transplant cyclophosphamide expanded the donor pool and was well tolerated in patients with SCD. However, the rate of secondary graft failure was high, at 43%.

“We hypothesized that increasing the amount of radiation that was given to these patients, making the regimen absolutely more intensive, will help us to overcome this rate of graft failure and retain the tolerability of the regimen,” Dr Bolaños-Meade said.

He and his colleagues tested this theory in 12 patients with SCD and 5 with beta-thalassemia.

The SCD patients had a median age of 26 (range, 6-31), and most (n=8) were female. Ten were African-American, and 2 were of Arab descent.

All SCD patients had at least 2 hospital admissions in the last 2 years, 5 had osteonecrosis, 3 were transfusion-dependent, 2 had a history of acute chest syndrome, and 1 patient had changes in brain magnetic resonance imaging.

The thalassemia patients had a median age of 7 (range, 6-16). Four were female, and all 5 were of Arab descent. All patients were transfusion-dependent from infancy.

Treatment

All patients received antithymocyte globulin (rabbit) at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, fludarabine at 30 mg/m² on days -6 to -2, cyclophosphamide at 14.5 mg/kg on days -6 and -5, and total body irradiation at 400 cGy on day -1.

Patients received unmanipulated bone marrow that was collected and infused on day 0. Donors included 1 aunt, 4 brothers, 3 sisters, 5 mothers, and 4 fathers. There were 2 major ABO incompatible pairs, 5 minor ABO incompatible pairs, and 10 ABO compatible pairs.

For GVHD prophylaxis, patients received 50 mg/kg/day of cyclophosphamide on days 3 and 4, sirolimus (levels of 5-10 ng/dl) from days 5 to 365, and mycophenolate mofetil at 1 g every 8 hours from days 5 to 35.

Efficacy

All 17 patients are still alive at a median follow-up of 15 months (range, 3-34).

“Of all the patients transplanted, we only observed 1 graft failure,” Dr Bolaños-Meade said. “This is in sharp contrast to the 40% graft failure in our prior study.”

Thirteen patients achieved full donor chimerism, and 3 had mixed chimerism.

Four of the 5 beta-thalassemia patients achieved full donor chimerism, and 1 had mixed chimerism. All 5 patients became transfusion-independent.

Eleven of the 12 SCD patients engrafted, and 9 achieved full donor chimerism.

All but one of the engrafted SCD patients became transfusion-independent. The exception was a mixed chimeric patient who had a major ABO mismatched donor. The patient remains transfusion-dependent more than 30 months after BMT.

“This is the main problem we have seen in all our sickle cell and hemoglobinopathy experiences,” Dr Bolaños-Meade said. “If you have a major ABO incompatibility, and there’s mixed chimerism, you’re asking for trouble.”

Toxicity

All SCD patients had sickle cell crises after antithymocyte globulin. Other toxicities included sirolimus-induced diabetes in 1 patient, worsening of Meniere’s disease in 1 patient, and BK cystitis in 1 patient.

Two patients developed grade 2 acute GVHD, and 1 developed grade 3 acute GVHD. Three patients had chronic GVHD, 2 mild and 1 moderate.

However, all cases of GVHD resolved. And, of the 8 engrafted patients with more than 1 year of follow-up, 6 are off systemic immunosuppression.

Javier Bolaños-Meade, MD

SALT LAKE CITY—Cure of severe hemoglobinopathies is now possible for most patients, according to a speaker at the 2018 BMT Tandem Meetings.

Results of a small study suggest that nonmyeloablative haploidentical bone marrow transplant (minihaplo-BMT), when used with 400 cGy total body irradiation and post-transplant cyclophosphamide, can cure sickle cell disease (SCD) and beta-thalassemia while conferring limited toxicity.

“This is our second study showing that you can certainly get rid of these conditions using haploidentical donors and, also, that you can cure these conditions with a nonmyeloablative regimen,” said Javier Bolaños-Meade, MD, of Johns Hopkins University in Baltimore, Maryland.

“What we saw [in the current study] is that increasing the total body irradiation from 200 cGy to 400 cGy can overcome the very high rate of graft failure we observed in our prior study.”

However, the results also suggest that major ABO incompatible donors should be avoided.

Dr Bolaños-Meade presented these findings as a late-breaking abstract (LBA3) at this year’s BMT Tandem Meetings.

He began the presentation by pointing out that allogeneic BMT is the only potential cure for SCD and beta-thalassemia. Unfortunately, most of these patients have been excluded from transplant due to a lack of matched donors, concerns over graft-vs-host disease (GVHD), and/or compromised end organ function precluding them from myeloablative conditioning.

With a prior study, Dr Bolaños-Meade and his colleagues found that minihaplo-BMT with post-transplant cyclophosphamide expanded the donor pool and was well tolerated in patients with SCD. However, the rate of secondary graft failure was high, at 43%.

“We hypothesized that increasing the amount of radiation that was given to these patients, making the regimen absolutely more intensive, will help us to overcome this rate of graft failure and retain the tolerability of the regimen,” Dr Bolaños-Meade said.

He and his colleagues tested this theory in 12 patients with SCD and 5 with beta-thalassemia.

The SCD patients had a median age of 26 (range, 6-31), and most (n=8) were female. Ten were African-American, and 2 were of Arab descent.

All SCD patients had at least 2 hospital admissions in the last 2 years, 5 had osteonecrosis, 3 were transfusion-dependent, 2 had a history of acute chest syndrome, and 1 patient had changes in brain magnetic resonance imaging.

The thalassemia patients had a median age of 7 (range, 6-16). Four were female, and all 5 were of Arab descent. All patients were transfusion-dependent from infancy.

Treatment

All patients received antithymocyte globulin (rabbit) at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, fludarabine at 30 mg/m² on days -6 to -2, cyclophosphamide at 14.5 mg/kg on days -6 and -5, and total body irradiation at 400 cGy on day -1.

Patients received unmanipulated bone marrow that was collected and infused on day 0. Donors included 1 aunt, 4 brothers, 3 sisters, 5 mothers, and 4 fathers. There were 2 major ABO incompatible pairs, 5 minor ABO incompatible pairs, and 10 ABO compatible pairs.

For GVHD prophylaxis, patients received 50 mg/kg/day of cyclophosphamide on days 3 and 4, sirolimus (levels of 5-10 ng/dl) from days 5 to 365, and mycophenolate mofetil at 1 g every 8 hours from days 5 to 35.

Efficacy

All 17 patients are still alive at a median follow-up of 15 months (range, 3-34).

“Of all the patients transplanted, we only observed 1 graft failure,” Dr Bolaños-Meade said. “This is in sharp contrast to the 40% graft failure in our prior study.”

Thirteen patients achieved full donor chimerism, and 3 had mixed chimerism.

Four of the 5 beta-thalassemia patients achieved full donor chimerism, and 1 had mixed chimerism. All 5 patients became transfusion-independent.

Eleven of the 12 SCD patients engrafted, and 9 achieved full donor chimerism.

All but one of the engrafted SCD patients became transfusion-independent. The exception was a mixed chimeric patient who had a major ABO mismatched donor. The patient remains transfusion-dependent more than 30 months after BMT.

“This is the main problem we have seen in all our sickle cell and hemoglobinopathy experiences,” Dr Bolaños-Meade said. “If you have a major ABO incompatibility, and there’s mixed chimerism, you’re asking for trouble.”

Toxicity

All SCD patients had sickle cell crises after antithymocyte globulin. Other toxicities included sirolimus-induced diabetes in 1 patient, worsening of Meniere’s disease in 1 patient, and BK cystitis in 1 patient.

Two patients developed grade 2 acute GVHD, and 1 developed grade 3 acute GVHD. Three patients had chronic GVHD, 2 mild and 1 moderate.

However, all cases of GVHD resolved. And, of the 8 engrafted patients with more than 1 year of follow-up, 6 are off systemic immunosuppression.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

Systemic lupus erythematosus

Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.

Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.

The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).

For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”

“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.

The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
 

Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing

Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).

“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.

That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.

Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).

“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.

He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
 

Implications of ultrasound enthesitis in early spondyloarthritis

French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.

It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).

“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.

He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.

The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).

Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.

[email protected]

MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

Systemic lupus erythematosus

Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.

Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.

The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).

For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”

“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.

The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
 

Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing

Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).

“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.

That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.

Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).

“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.

He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
 

Implications of ultrasound enthesitis in early spondyloarthritis

French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.

It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).

“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.

He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.

The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).

Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.

[email protected]

MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

Systemic lupus erythematosus

Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.

Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.

The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).

For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”

“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.

The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
 

Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing

Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).

“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.

That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.

Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).

“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.

He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
 

Implications of ultrasound enthesitis in early spondyloarthritis

French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.

It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).

“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.

He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.

The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).

Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.

[email protected]

TAMPA, FLA. – Most psychiatrists believe that the so-called “Goldwater Rule” should be amended if an informal poll conducted at the annual meeting of the American College of Psychiatrists reflects dominant opinion.

The poll was conducted at the end of a debate between Nada L. Stotland, MD, who argued for no change, and Steven S. Sharfstein, MD, who argued that the ethical standard may have made sense when created in 1973 “but is now outmoded.”

Ted Bosworth/Frontline Medical News

The American Psychiatric Association introduced what is widely known as the Goldwater Rule into the APA code of ethics following an infamous survey of psychiatrists published in 1964. In that survey, the respondents overwhelmingly expressed the opinion that Barry Goldwater, the Arizona senator and 1964 candidate for president of the United States, was unfit to serve, an outcome that many considered an embarrassment for the APA.

As written, the ethical standard introduced by the APA proscribes psychiatrists from pronouncing a diagnosis of mental illness in public figures who they have not examined. The standard was later amended to disallow any professional opinion on mental health in public figures, not just a diagnosis.

This standard, always controversial, has been increasingly challenged as a result of concerns expressed frequently in public forums about the mental health of the current president. The moderator of the debate, John M. Oldman, MD, chair for personality disorders in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, commented that President Donald Trump “may be the death of the Goldwater rule.”

Even though not all agreed that a psychiatric diagnosis requires a face-to-face evaluation, the debate centered on the justification for banning psychiatrists from offering any opinion about the mental health of a public figure. Can an opinion be justified on the basis of First Amendment guarantees of free speech if the speaker identifies him or herself as a psychiatrist?

Dr. Sharfstein, who is president emeritus, Sheppard Pratt Health System, Baltimore, concluded that this prohibition is too far reaching. By his interpretation, psychiatrists who call a public figure “a jerk” are potentially violating the Goldwater Rule. Although he conceded that he is sensitive to the etiquette of demeaning public figures when speaking in the capacity of a psychiatrist, he said that banning the expression of opinions “is unenforceable.”

Dr. Stotland, professor of psychiatry at Rush Medical College, Chicago, disagreed. She argued that comments on mental health status expressed by a psychiatrist carry different weight than other citizens. Like boxers, whose fists are considered legal weapons in some states, a psychiatrist “should give up the right to express casual opinions” about psychopathology in a public figure, she said.

As professional opinions will almost certainly differ between psychiatrists, Dr. Stotland also suggested that an inevitable variety of opinions expressed by different psychiatrists about a public figure is not likely to contribute usefully to the general discourse. “Dissension in our public remarks undermines the credibility of our profession,” she said.

Although Dr. Sharfstein questioned whether psychiatrists have an ethical or moral obligation to “make the profession look good,” he conceded that there is room for civility when making pronouncements about the mental health status of public figures. Nevertheless, he reiterated that a ban on the expression of opinion is untenable. Citing the words of another critic of the Goldwater Rule, he argued, “Every psychiatrist has a first amendment right to make an idiot of themselves.”

For her part, Dr. Stotland suggested it is reasonable to ask whether psychiatrists questioning the mental health of a political leader are offering “a diagnosis or an accusation.” She cautioned about “using psychiatry as a weapon” in political debate.

Distinguishing professional from political opinions when speaking about mental health is a “slippery slope,” agreed Dr. Sharfstein, but he expressed concern about the ethics of not speaking out when a psychiatrist is convinced that a leader is psychologically unstable.

In the informal vote following the debate, the audience was provided with four options: retain the Goldwater Rule, abandon the Goldwater Rule, modify the Goldwater Rule, or abstain from voting. A large majority of the audience voted for a modification, overwhelming all three of the other options. Yet, it could not be determined from the show of hands what specific changes the audience members had in mind.

Dr. Oldham, Dr. Sharfstein, and Dr. Stotland reported no conflicts of interest relevant to this topic.

TAMPA, FLA. – Most psychiatrists believe that the so-called “Goldwater Rule” should be amended if an informal poll conducted at the annual meeting of the American College of Psychiatrists reflects dominant opinion.

The poll was conducted at the end of a debate between Nada L. Stotland, MD, who argued for no change, and Steven S. Sharfstein, MD, who argued that the ethical standard may have made sense when created in 1973 “but is now outmoded.”

Ted Bosworth/Frontline Medical News

The American Psychiatric Association introduced what is widely known as the Goldwater Rule into the APA code of ethics following an infamous survey of psychiatrists published in 1964. In that survey, the respondents overwhelmingly expressed the opinion that Barry Goldwater, the Arizona senator and 1964 candidate for president of the United States, was unfit to serve, an outcome that many considered an embarrassment for the APA.

As written, the ethical standard introduced by the APA proscribes psychiatrists from pronouncing a diagnosis of mental illness in public figures who they have not examined. The standard was later amended to disallow any professional opinion on mental health in public figures, not just a diagnosis.

This standard, always controversial, has been increasingly challenged as a result of concerns expressed frequently in public forums about the mental health of the current president. The moderator of the debate, John M. Oldman, MD, chair for personality disorders in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, commented that President Donald Trump “may be the death of the Goldwater rule.”

Even though not all agreed that a psychiatric diagnosis requires a face-to-face evaluation, the debate centered on the justification for banning psychiatrists from offering any opinion about the mental health of a public figure. Can an opinion be justified on the basis of First Amendment guarantees of free speech if the speaker identifies him or herself as a psychiatrist?

Dr. Sharfstein, who is president emeritus, Sheppard Pratt Health System, Baltimore, concluded that this prohibition is too far reaching. By his interpretation, psychiatrists who call a public figure “a jerk” are potentially violating the Goldwater Rule. Although he conceded that he is sensitive to the etiquette of demeaning public figures when speaking in the capacity of a psychiatrist, he said that banning the expression of opinions “is unenforceable.”

Dr. Stotland, professor of psychiatry at Rush Medical College, Chicago, disagreed. She argued that comments on mental health status expressed by a psychiatrist carry different weight than other citizens. Like boxers, whose fists are considered legal weapons in some states, a psychiatrist “should give up the right to express casual opinions” about psychopathology in a public figure, she said.

As professional opinions will almost certainly differ between psychiatrists, Dr. Stotland also suggested that an inevitable variety of opinions expressed by different psychiatrists about a public figure is not likely to contribute usefully to the general discourse. “Dissension in our public remarks undermines the credibility of our profession,” she said.

Although Dr. Sharfstein questioned whether psychiatrists have an ethical or moral obligation to “make the profession look good,” he conceded that there is room for civility when making pronouncements about the mental health status of public figures. Nevertheless, he reiterated that a ban on the expression of opinion is untenable. Citing the words of another critic of the Goldwater Rule, he argued, “Every psychiatrist has a first amendment right to make an idiot of themselves.”

For her part, Dr. Stotland suggested it is reasonable to ask whether psychiatrists questioning the mental health of a political leader are offering “a diagnosis or an accusation.” She cautioned about “using psychiatry as a weapon” in political debate.

Distinguishing professional from political opinions when speaking about mental health is a “slippery slope,” agreed Dr. Sharfstein, but he expressed concern about the ethics of not speaking out when a psychiatrist is convinced that a leader is psychologically unstable.

In the informal vote following the debate, the audience was provided with four options: retain the Goldwater Rule, abandon the Goldwater Rule, modify the Goldwater Rule, or abstain from voting. A large majority of the audience voted for a modification, overwhelming all three of the other options. Yet, it could not be determined from the show of hands what specific changes the audience members had in mind.

Dr. Oldham, Dr. Sharfstein, and Dr. Stotland reported no conflicts of interest relevant to this topic.

TAMPA, FLA. – Most psychiatrists believe that the so-called “Goldwater Rule” should be amended if an informal poll conducted at the annual meeting of the American College of Psychiatrists reflects dominant opinion.

The poll was conducted at the end of a debate between Nada L. Stotland, MD, who argued for no change, and Steven S. Sharfstein, MD, who argued that the ethical standard may have made sense when created in 1973 “but is now outmoded.”

Ted Bosworth/Frontline Medical News

The American Psychiatric Association introduced what is widely known as the Goldwater Rule into the APA code of ethics following an infamous survey of psychiatrists published in 1964. In that survey, the respondents overwhelmingly expressed the opinion that Barry Goldwater, the Arizona senator and 1964 candidate for president of the United States, was unfit to serve, an outcome that many considered an embarrassment for the APA.

As written, the ethical standard introduced by the APA proscribes psychiatrists from pronouncing a diagnosis of mental illness in public figures who they have not examined. The standard was later amended to disallow any professional opinion on mental health in public figures, not just a diagnosis.

This standard, always controversial, has been increasingly challenged as a result of concerns expressed frequently in public forums about the mental health of the current president. The moderator of the debate, John M. Oldman, MD, chair for personality disorders in the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, commented that President Donald Trump “may be the death of the Goldwater rule.”

Even though not all agreed that a psychiatric diagnosis requires a face-to-face evaluation, the debate centered on the justification for banning psychiatrists from offering any opinion about the mental health of a public figure. Can an opinion be justified on the basis of First Amendment guarantees of free speech if the speaker identifies him or herself as a psychiatrist?

Dr. Sharfstein, who is president emeritus, Sheppard Pratt Health System, Baltimore, concluded that this prohibition is too far reaching. By his interpretation, psychiatrists who call a public figure “a jerk” are potentially violating the Goldwater Rule. Although he conceded that he is sensitive to the etiquette of demeaning public figures when speaking in the capacity of a psychiatrist, he said that banning the expression of opinions “is unenforceable.”

Dr. Stotland, professor of psychiatry at Rush Medical College, Chicago, disagreed. She argued that comments on mental health status expressed by a psychiatrist carry different weight than other citizens. Like boxers, whose fists are considered legal weapons in some states, a psychiatrist “should give up the right to express casual opinions” about psychopathology in a public figure, she said.

As professional opinions will almost certainly differ between psychiatrists, Dr. Stotland also suggested that an inevitable variety of opinions expressed by different psychiatrists about a public figure is not likely to contribute usefully to the general discourse. “Dissension in our public remarks undermines the credibility of our profession,” she said.

Although Dr. Sharfstein questioned whether psychiatrists have an ethical or moral obligation to “make the profession look good,” he conceded that there is room for civility when making pronouncements about the mental health status of public figures. Nevertheless, he reiterated that a ban on the expression of opinion is untenable. Citing the words of another critic of the Goldwater Rule, he argued, “Every psychiatrist has a first amendment right to make an idiot of themselves.”

For her part, Dr. Stotland suggested it is reasonable to ask whether psychiatrists questioning the mental health of a political leader are offering “a diagnosis or an accusation.” She cautioned about “using psychiatry as a weapon” in political debate.

Distinguishing professional from political opinions when speaking about mental health is a “slippery slope,” agreed Dr. Sharfstein, but he expressed concern about the ethics of not speaking out when a psychiatrist is convinced that a leader is psychologically unstable.

In the informal vote following the debate, the audience was provided with four options: retain the Goldwater Rule, abandon the Goldwater Rule, modify the Goldwater Rule, or abstain from voting. A large majority of the audience voted for a modification, overwhelming all three of the other options. Yet, it could not be determined from the show of hands what specific changes the audience members had in mind.

Dr. Oldham, Dr. Sharfstein, and Dr. Stotland reported no conflicts of interest relevant to this topic.

SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?

At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.

“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”

Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. The median time to loss of PASI 90 response was 15 weeks (23 weeks after last guselkumab dose) for patients randomized to the withdrawal group. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.

“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”

The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.

“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”

SOURCE: Gordon K et al. AAD 2018 Abstract 6748.

[email protected]

SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?

At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.

“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”

Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. The median time to loss of PASI 90 response was 15 weeks (23 weeks after last guselkumab dose) for patients randomized to the withdrawal group. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.

“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”

The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.

“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”

SOURCE: Gordon K et al. AAD 2018 Abstract 6748.

[email protected]

SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?

At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.

“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”

Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. The median time to loss of PASI 90 response was 15 weeks (23 weeks after last guselkumab dose) for patients randomized to the withdrawal group. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.

“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”

The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.

“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”

SOURCE: Gordon K et al. AAD 2018 Abstract 6748.

[email protected]

MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?

At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.

Bruce Jancin/Frontline Medical News

Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.

Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.

“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).

Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?

At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.

Bruce Jancin/Frontline Medical News

Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.

Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.

“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).

Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

[email protected]

MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?

At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.

Bruce Jancin/Frontline Medical News

Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.

Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.

“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).

Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.

[email protected]

TAMPA, FLA. – Although there are very limited data on the risks, frequency, or consequences of sexual boundary violations in psychiatry, a personal experience evaluating, treating, or consulting in 300 such cases suggests that violators often consider their behavior to be justified, at least initially, according to an overview presented at the annual meeting of the American College of Psychiatrists.

“The capacity for individuals to rationalize their actions is just extraordinary,” said Glen O. Gabbard, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston. He explained that many, if not all, violators are familiar with the reasons that sex between therapists and patients is unethical, but they typically consider their specific case exceptional.

In his anecdotal series of cases, Dr. Gabbard noted that 85% of the violators have been male therapists crossing sexual boundaries with female patients, but he cautioned that this might be a skewed sample.

“Males who have sex with female therapists often feel triumphant,” Dr. Gabbard said. This may explain why complaints by male patients against female therapists are relatively uncommon. However, citing several cases, Dr. Gabbard said that the general outrage is typically greater when a female therapist is the perpetrator.

Regardless of the circumstances, sexual relations with a patient are always a breach of fiduciary duty, Dr. Gabbard said. Nothing justifies this behavior. For example, a subsequent marriage between a therapist and his or her patient is not a mitigating proof of a justifiable romance. Rather, not least because of the unequal power dynamics between a therapist and his or her patient, Dr. Gabbard warned that such marriages have a strong potential for adverse long-term consequences for the well being of the patient.

Defenses are needed against sexual boundary violations, because sexual attraction involves complex dynamics with insidious effects on thought processes that are not always clear to the individuals involved. The line between flattery, charm, admiration, and friendliness can blur progressively into a sexualized relationship, particularly if physical contact, such as hugs, provides an opportunity to express sexual attraction.

Clinicians at risk of blurring these lines in the course of their efforts to help a patient should consider a key principle of lifeguarding, Dr. Gabbard said. He explained that lifeguards are taught to make sure they are safe before engaging in a rescue. This reason, according to Dr. Gabbard, is, “Drowning victims can take you with them.”

Dr. Gabbard reported no relevant conflicts of interest.

TAMPA, FLA. – Although there are very limited data on the risks, frequency, or consequences of sexual boundary violations in psychiatry, a personal experience evaluating, treating, or consulting in 300 such cases suggests that violators often consider their behavior to be justified, at least initially, according to an overview presented at the annual meeting of the American College of Psychiatrists.

“The capacity for individuals to rationalize their actions is just extraordinary,” said Glen O. Gabbard, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston. He explained that many, if not all, violators are familiar with the reasons that sex between therapists and patients is unethical, but they typically consider their specific case exceptional.

In his anecdotal series of cases, Dr. Gabbard noted that 85% of the violators have been male therapists crossing sexual boundaries with female patients, but he cautioned that this might be a skewed sample.

“Males who have sex with female therapists often feel triumphant,” Dr. Gabbard said. This may explain why complaints by male patients against female therapists are relatively uncommon. However, citing several cases, Dr. Gabbard said that the general outrage is typically greater when a female therapist is the perpetrator.

Regardless of the circumstances, sexual relations with a patient are always a breach of fiduciary duty, Dr. Gabbard said. Nothing justifies this behavior. For example, a subsequent marriage between a therapist and his or her patient is not a mitigating proof of a justifiable romance. Rather, not least because of the unequal power dynamics between a therapist and his or her patient, Dr. Gabbard warned that such marriages have a strong potential for adverse long-term consequences for the well being of the patient.

Defenses are needed against sexual boundary violations, because sexual attraction involves complex dynamics with insidious effects on thought processes that are not always clear to the individuals involved. The line between flattery, charm, admiration, and friendliness can blur progressively into a sexualized relationship, particularly if physical contact, such as hugs, provides an opportunity to express sexual attraction.

Clinicians at risk of blurring these lines in the course of their efforts to help a patient should consider a key principle of lifeguarding, Dr. Gabbard said. He explained that lifeguards are taught to make sure they are safe before engaging in a rescue. This reason, according to Dr. Gabbard, is, “Drowning victims can take you with them.”

Dr. Gabbard reported no relevant conflicts of interest.

TAMPA, FLA. – Although there are very limited data on the risks, frequency, or consequences of sexual boundary violations in psychiatry, a personal experience evaluating, treating, or consulting in 300 such cases suggests that violators often consider their behavior to be justified, at least initially, according to an overview presented at the annual meeting of the American College of Psychiatrists.

“The capacity for individuals to rationalize their actions is just extraordinary,” said Glen O. Gabbard, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine, Houston. He explained that many, if not all, violators are familiar with the reasons that sex between therapists and patients is unethical, but they typically consider their specific case exceptional.

In his anecdotal series of cases, Dr. Gabbard noted that 85% of the violators have been male therapists crossing sexual boundaries with female patients, but he cautioned that this might be a skewed sample.

“Males who have sex with female therapists often feel triumphant,” Dr. Gabbard said. This may explain why complaints by male patients against female therapists are relatively uncommon. However, citing several cases, Dr. Gabbard said that the general outrage is typically greater when a female therapist is the perpetrator.

Regardless of the circumstances, sexual relations with a patient are always a breach of fiduciary duty, Dr. Gabbard said. Nothing justifies this behavior. For example, a subsequent marriage between a therapist and his or her patient is not a mitigating proof of a justifiable romance. Rather, not least because of the unequal power dynamics between a therapist and his or her patient, Dr. Gabbard warned that such marriages have a strong potential for adverse long-term consequences for the well being of the patient.

Defenses are needed against sexual boundary violations, because sexual attraction involves complex dynamics with insidious effects on thought processes that are not always clear to the individuals involved. The line between flattery, charm, admiration, and friendliness can blur progressively into a sexualized relationship, particularly if physical contact, such as hugs, provides an opportunity to express sexual attraction.

Clinicians at risk of blurring these lines in the course of their efforts to help a patient should consider a key principle of lifeguarding, Dr. Gabbard said. He explained that lifeguards are taught to make sure they are safe before engaging in a rescue. This reason, according to Dr. Gabbard, is, “Drowning victims can take you with them.”

Dr. Gabbard reported no relevant conflicts of interest.

Women aged 35 years and older had a higher risk for giving birth before 34 weeks of gestation but only women aged 35-39 years had a higher risk for stillbirth, according to research published online in Obstetrics & Gynecology.

Line Elmerdahl Frederiksen of Aarhus (Denmark) University and her colleagues compared outcomes for women aged 35-39 years and women aged 40 years or older with outcomes for women aged 20-34 years.

The researchers analyzed 369,516 singleton pregnancies in women who had a first-trimester screening between 11 and 14 weeks of gestation at a public hospital in Denmark between January 2008 and December 2014.

“In this study, we were able to include detected chromosomal abnormalities and congenital malformations from an early gestational age, which in other studies would not have been available for assessment,” the authors wrote. The researchers also included miscarriage, birth before 34 weeks of gestation, and stillbirth outcomes in their analysis.

The researchers reported an increased risk for giving birth before 34 weeks of gestation for women aged 35-39 years (odds ratio, 1.25) and for women aged 40 years or older (OR, 1.66). The authors wrote that this finding was contradictory to previously reported data and noted that obstetric complications, which are known to increase with age, could explain their finding.

Women aged 35-39 years had a higher risk for stillbirth, compared with women aged 20-34 years (OR, 1.43), according to the study. However, the researchers did not observe a similar risk for women aged 40 years or older. “This counterintuitive finding could possibly occur because induction of labor for comorbidities is more likely in women older than 40 years,” wrote Ms. Frederiksen and her coauthors.

The researchers reported increased risk for both miscarriage and chromosomal abnormalities for women aged 35-39 years and women aged 40 years or older, adding to the previously published risk association for older women. Risk for congenital malformations did not appear to differ between maternal age groups, which was also consistent with previous data.

In a composite risk analysis, researchers found an increased risk for an adverse pregnancy outcome for women aged 35-39 years (OR, 1.29) and women aged 40 years or older (OR, 2.02).

The authors reported no potential conflicts of interest.

[email protected]

SOURCE: Frederiksen L et al. Obstet Gynecol. 2018 Feb 5. doi: 10.1097/AOG.0000000000002504.

Women aged 35 years and older had a higher risk for giving birth before 34 weeks of gestation but only women aged 35-39 years had a higher risk for stillbirth, according to research published online in Obstetrics & Gynecology.

Line Elmerdahl Frederiksen of Aarhus (Denmark) University and her colleagues compared outcomes for women aged 35-39 years and women aged 40 years or older with outcomes for women aged 20-34 years.

The researchers analyzed 369,516 singleton pregnancies in women who had a first-trimester screening between 11 and 14 weeks of gestation at a public hospital in Denmark between January 2008 and December 2014.

“In this study, we were able to include detected chromosomal abnormalities and congenital malformations from an early gestational age, which in other studies would not have been available for assessment,” the authors wrote. The researchers also included miscarriage, birth before 34 weeks of gestation, and stillbirth outcomes in their analysis.

The researchers reported an increased risk for giving birth before 34 weeks of gestation for women aged 35-39 years (odds ratio, 1.25) and for women aged 40 years or older (OR, 1.66). The authors wrote that this finding was contradictory to previously reported data and noted that obstetric complications, which are known to increase with age, could explain their finding.

Women aged 35-39 years had a higher risk for stillbirth, compared with women aged 20-34 years (OR, 1.43), according to the study. However, the researchers did not observe a similar risk for women aged 40 years or older. “This counterintuitive finding could possibly occur because induction of labor for comorbidities is more likely in women older than 40 years,” wrote Ms. Frederiksen and her coauthors.

The researchers reported increased risk for both miscarriage and chromosomal abnormalities for women aged 35-39 years and women aged 40 years or older, adding to the previously published risk association for older women. Risk for congenital malformations did not appear to differ between maternal age groups, which was also consistent with previous data.

In a composite risk analysis, researchers found an increased risk for an adverse pregnancy outcome for women aged 35-39 years (OR, 1.29) and women aged 40 years or older (OR, 2.02).

The authors reported no potential conflicts of interest.

[email protected]

SOURCE: Frederiksen L et al. Obstet Gynecol. 2018 Feb 5. doi: 10.1097/AOG.0000000000002504.

Women aged 35 years and older had a higher risk for giving birth before 34 weeks of gestation but only women aged 35-39 years had a higher risk for stillbirth, according to research published online in Obstetrics & Gynecology.

Line Elmerdahl Frederiksen of Aarhus (Denmark) University and her colleagues compared outcomes for women aged 35-39 years and women aged 40 years or older with outcomes for women aged 20-34 years.

The researchers analyzed 369,516 singleton pregnancies in women who had a first-trimester screening between 11 and 14 weeks of gestation at a public hospital in Denmark between January 2008 and December 2014.

“In this study, we were able to include detected chromosomal abnormalities and congenital malformations from an early gestational age, which in other studies would not have been available for assessment,” the authors wrote. The researchers also included miscarriage, birth before 34 weeks of gestation, and stillbirth outcomes in their analysis.

The researchers reported an increased risk for giving birth before 34 weeks of gestation for women aged 35-39 years (odds ratio, 1.25) and for women aged 40 years or older (OR, 1.66). The authors wrote that this finding was contradictory to previously reported data and noted that obstetric complications, which are known to increase with age, could explain their finding.

Women aged 35-39 years had a higher risk for stillbirth, compared with women aged 20-34 years (OR, 1.43), according to the study. However, the researchers did not observe a similar risk for women aged 40 years or older. “This counterintuitive finding could possibly occur because induction of labor for comorbidities is more likely in women older than 40 years,” wrote Ms. Frederiksen and her coauthors.

The researchers reported increased risk for both miscarriage and chromosomal abnormalities for women aged 35-39 years and women aged 40 years or older, adding to the previously published risk association for older women. Risk for congenital malformations did not appear to differ between maternal age groups, which was also consistent with previous data.

In a composite risk analysis, researchers found an increased risk for an adverse pregnancy outcome for women aged 35-39 years (OR, 1.29) and women aged 40 years or older (OR, 2.02).

The authors reported no potential conflicts of interest.

[email protected]

SOURCE: Frederiksen L et al. Obstet Gynecol. 2018 Feb 5. doi: 10.1097/AOG.0000000000002504.

SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.

Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.

Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.

However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”

The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.

“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”

To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].

The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.

[email protected]

SOURCE: Gelfand J et al. AAD 2018 Abstract 6645

SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.

Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.

Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.

However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”

The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.

“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”

To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].

The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.

[email protected]

SOURCE: Gelfand J et al. AAD 2018 Abstract 6645

SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.

Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.

Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.

However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”

The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.

“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”

To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].

The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.

[email protected]

SOURCE: Gelfand J et al. AAD 2018 Abstract 6645

MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.

“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.

Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.

Bruce Jancin/Frontline Medical News

Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.

Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
 

Potential therapeutic strategies targeting NETosis

Many different targets are in early-stage studies aimed at inhibiting neutrophil activation and NETosis. The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.

Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.

The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.

“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.

She reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.

“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.

Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.

Bruce Jancin/Frontline Medical News

Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.

Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
 

Potential therapeutic strategies targeting NETosis

Many different targets are in early-stage studies aimed at inhibiting neutrophil activation and NETosis. The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.

Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.

The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.

“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.

She reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.

“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.

Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.

Bruce Jancin/Frontline Medical News

Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.

Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
 

Potential therapeutic strategies targeting NETosis

Many different targets are in early-stage studies aimed at inhibiting neutrophil activation and NETosis. The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.

Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.

The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.

“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.

She reported having no financial conflicts regarding her presentation.

[email protected]