MAUI, HAWAII – One of the most important steps to take when a child has received a biopsy-confirmed diagnosis of localized scleroderma is to sit down with the family and explain the rationale for the aggressive therapies to come, Anne M. Stevens, MD, PhD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

It can be a tough sell at first, especially when a child has only a small red streak on the nose and perhaps a subtle linear lesion on the forehead or scalp. But the family has to come to understand that this is a serious, chronic, progressive fibrotic disease.

“Talk about what a big impact this disease can have on growth of a limb and the normal life of a child because of the cosmetic appearance. Explain that the length of treatment course is based on the long-term outcomes and quality of life. This discussion is usually sufficient” to convince people to give their children “these pretty serious medications,” said Dr. Stevens, professor of pediatrics and head of the division of pediatric rheumatology at the University of Washington, Seattle.

“The treatment goal is to control inflammation and prevent damage in these patients, who we like to catch very early, when it’s a subtle lesion,” she added.
 

The biggest problem

The biggest contributors to poor quality of life in patients with juvenile localized scleroderma are the extracutaneous manifestations, which occur in up to 50% of cases. Joint pain occurs in roughly 20% of patients, joint contractures due to fibrosis of skin and/or tendons in 30%, and myalgia with or without myositis in 15%. Muscle atrophy due to the deep component of the scleroderma can occur. Moreover, growth problems – especially leg or arm length discrepancies – happen in about 20% of patients in prospective studies. These growth problems may not be obvious until a child enters a growth spurt, at which point there is a limited ability to achieve improvement. That’s why Dr. Stevens recommends that every child with localized scleroderma should get a full joint exam at every visit, with measurement and photos of lesions and recording of all erythematous, violaceous, and waxy-hued areas. And if there are lesions on the head, annual eye exams are warranted.

The prevalence of juvenile localized scleroderma in the United States is about 3 per 100,000, with a mean age of onset of 8.2 years. That makes it 100-fold more common than pediatric systemic sclerosis.
 

The treatment ladder

There are no Food and Drug Administration–approved medications for localized scleroderma in children. It’s all off label. That being said, there is strong consensus among members of the Childhood Arthritis and Rheumatology Research Alliance that the first-line therapy is methotrexate at 15 mg/m² or a maximum of 20 mg/week plus intravenous corticosteroids weaned over the course of 3-6 months. This is the treatment regimen with the best supporting evidence of safety and efficacy, including a single Italian randomized, double-blind, placebo-controlled clinical trial (Arthritis Rheum. 2011 Jul;63[7]:1998-2006) and an accompanying long-term, open-label follow-up study (J Am Acad Dermatol. 2012 Dec;67[6]:1151-6).

All of the other treatments she uses for juvenile localized scleroderma – mycophenolate mofetil (CellCept), abatacept (Orencia), tocilizumab (Actemra), and occasionally others – are backed only by a smattering of small case series. However, given the serious potential trajectory of this disease, that modest evidence base has been sufficient for her to receive insurance coverage approval of these agents.

In the randomized trial of first-line methotrexate, 48 of 65 patients treated with methotrexate plus steroid (74%) were responders. And among those 48 responders, 35 (73%) maintained a clinical remission for a mean of 25 months off-drug, while another 13 (27%) were in clinical remission on methotrexate. Twenty-eight patients developed side effects that were generally mild; no one required treatment discontinuation. At the 5-year mark, after an average of an initial 2 years on methotrexate, half of the patients were in a sustained clinical remission, which Dr. Stevens deemed “pretty good” considering the well established and manageable safety profile of the drug.

If a patient fails to respond to methotrexate plus corticosteroids within a few months or later experiences disease progression, Dr. Stevens’ second-line therapy is mycophenolate mofetil in conjunction with corticosteroids. Its use in arresting juvenile localized scleroderma is supported by two favorable published case series, the largest of which includes 10 patients (Rheumatology [Oxford]. 2009 Nov;48[11]:1410-3).

Dr. Stevens’ third-line therapy is intravenous abatacept at 10 mg/kg monthly along with intravenous methylprednisolone at 500 mg/week. There are five published case series, the most recent and largest of which included 13 adult patients, two of whom had en coup de sabre lesions (Acta Derm Venereol. 2018 Apr 16;98[4]:465-6). The biologic also shows promise in patients with advanced severe disease with deep tissue involvement (Semin Arthritis Rheum. 2017 Jun;46[6]:775-81). And abatacept has a plausible mechanism of action in localized scleroderma: French investigators have shown it induces regression of skin fibrosis in a mouse model of the disease (Ann Rheum Dis. 2016 Dec;75[12]:2142-9).

Her fourth-line strategy is the anti-interleukin-6 agent tocilizumab, again in conjunction with corticosteroids. In a translational study, tocilizumab has been shown to normalize dermal fibroblasts and collagen in patients with systemic sclerosis (Ann Rheum Dis. 2018 Sep;77[9]:1362-71). And there have been two promising small retrospective case series as well. A more definitive clinical trial is planned.

Dr. Stevens said that when starting a biologic agent in a child with localized scleroderma, she routinely adds methotrexate until the disease is under control.

Drugs supported by case reports and worth considering on an individual basis as a last resort are hydroxychloroquine, azathioprine, cyclosporine, and imatinib mesylate (Gleevec).

For mild, superficial lesions that don’t cross joints, ultraviolet light A phototherapy is a therapeutic option. It displayed significant benefit in a systematic review and meta-analysis of 19 studies comparing it to methotrexate, although the results with methotrexate were deemed superior (Semin Arthritis Rheum. 2018 Dec;48[3]:495-503).

The pros and cons of getting a baseline brain MRI

Children with localized scleroderma have increased rates of severe headache, peripheral neuropathy, complex partial seizures, and stroke. So it had been Dr. Stevens’ routine practice to obtain an initial brain MRI at the time of diagnosis. Of late, though, she has reconsidered that practice.

“The problem is that some patients with abnormal MRI lesions have no CNS disease at all, and there are also a fair number of patients with a normal MRI who have CNS symptoms. So in our practice we’re pulling back on doing screening MRIs because we don’t know what to do with the findings, and it just makes everybody worried,” she said.

However, if a child with localized scleroderma develops headaches, seizures, neuropathies, or other CNS symptoms, then by all means get an MRI, and if it shows findings such as brain atrophy, white matter lesions, calcifications, or leptomeningeal enhancement, consider treatment, she added.

Dr. Stevens reported receiving research funding from Kineta and Seattle Genetics.

bjancin@mdedge.com

MAUI, HAWAII – One of the most important steps to take when a child has received a biopsy-confirmed diagnosis of localized scleroderma is to sit down with the family and explain the rationale for the aggressive therapies to come, Anne M. Stevens, MD, PhD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

It can be a tough sell at first, especially when a child has only a small red streak on the nose and perhaps a subtle linear lesion on the forehead or scalp. But the family has to come to understand that this is a serious, chronic, progressive fibrotic disease.

“Talk about what a big impact this disease can have on growth of a limb and the normal life of a child because of the cosmetic appearance. Explain that the length of treatment course is based on the long-term outcomes and quality of life. This discussion is usually sufficient” to convince people to give their children “these pretty serious medications,” said Dr. Stevens, professor of pediatrics and head of the division of pediatric rheumatology at the University of Washington, Seattle.

“The treatment goal is to control inflammation and prevent damage in these patients, who we like to catch very early, when it’s a subtle lesion,” she added.
 

The biggest problem

The biggest contributors to poor quality of life in patients with juvenile localized scleroderma are the extracutaneous manifestations, which occur in up to 50% of cases. Joint pain occurs in roughly 20% of patients, joint contractures due to fibrosis of skin and/or tendons in 30%, and myalgia with or without myositis in 15%. Muscle atrophy due to the deep component of the scleroderma can occur. Moreover, growth problems – especially leg or arm length discrepancies – happen in about 20% of patients in prospective studies. These growth problems may not be obvious until a child enters a growth spurt, at which point there is a limited ability to achieve improvement. That’s why Dr. Stevens recommends that every child with localized scleroderma should get a full joint exam at every visit, with measurement and photos of lesions and recording of all erythematous, violaceous, and waxy-hued areas. And if there are lesions on the head, annual eye exams are warranted.

The prevalence of juvenile localized scleroderma in the United States is about 3 per 100,000, with a mean age of onset of 8.2 years. That makes it 100-fold more common than pediatric systemic sclerosis.
 

The treatment ladder

There are no Food and Drug Administration–approved medications for localized scleroderma in children. It’s all off label. That being said, there is strong consensus among members of the Childhood Arthritis and Rheumatology Research Alliance that the first-line therapy is methotrexate at 15 mg/m² or a maximum of 20 mg/week plus intravenous corticosteroids weaned over the course of 3-6 months. This is the treatment regimen with the best supporting evidence of safety and efficacy, including a single Italian randomized, double-blind, placebo-controlled clinical trial (Arthritis Rheum. 2011 Jul;63[7]:1998-2006) and an accompanying long-term, open-label follow-up study (J Am Acad Dermatol. 2012 Dec;67[6]:1151-6).

All of the other treatments she uses for juvenile localized scleroderma – mycophenolate mofetil (CellCept), abatacept (Orencia), tocilizumab (Actemra), and occasionally others – are backed only by a smattering of small case series. However, given the serious potential trajectory of this disease, that modest evidence base has been sufficient for her to receive insurance coverage approval of these agents.

In the randomized trial of first-line methotrexate, 48 of 65 patients treated with methotrexate plus steroid (74%) were responders. And among those 48 responders, 35 (73%) maintained a clinical remission for a mean of 25 months off-drug, while another 13 (27%) were in clinical remission on methotrexate. Twenty-eight patients developed side effects that were generally mild; no one required treatment discontinuation. At the 5-year mark, after an average of an initial 2 years on methotrexate, half of the patients were in a sustained clinical remission, which Dr. Stevens deemed “pretty good” considering the well established and manageable safety profile of the drug.

If a patient fails to respond to methotrexate plus corticosteroids within a few months or later experiences disease progression, Dr. Stevens’ second-line therapy is mycophenolate mofetil in conjunction with corticosteroids. Its use in arresting juvenile localized scleroderma is supported by two favorable published case series, the largest of which includes 10 patients (Rheumatology [Oxford]. 2009 Nov;48[11]:1410-3).

Dr. Stevens’ third-line therapy is intravenous abatacept at 10 mg/kg monthly along with intravenous methylprednisolone at 500 mg/week. There are five published case series, the most recent and largest of which included 13 adult patients, two of whom had en coup de sabre lesions (Acta Derm Venereol. 2018 Apr 16;98[4]:465-6). The biologic also shows promise in patients with advanced severe disease with deep tissue involvement (Semin Arthritis Rheum. 2017 Jun;46[6]:775-81). And abatacept has a plausible mechanism of action in localized scleroderma: French investigators have shown it induces regression of skin fibrosis in a mouse model of the disease (Ann Rheum Dis. 2016 Dec;75[12]:2142-9).

Her fourth-line strategy is the anti-interleukin-6 agent tocilizumab, again in conjunction with corticosteroids. In a translational study, tocilizumab has been shown to normalize dermal fibroblasts and collagen in patients with systemic sclerosis (Ann Rheum Dis. 2018 Sep;77[9]:1362-71). And there have been two promising small retrospective case series as well. A more definitive clinical trial is planned.

Dr. Stevens said that when starting a biologic agent in a child with localized scleroderma, she routinely adds methotrexate until the disease is under control.

Drugs supported by case reports and worth considering on an individual basis as a last resort are hydroxychloroquine, azathioprine, cyclosporine, and imatinib mesylate (Gleevec).

For mild, superficial lesions that don’t cross joints, ultraviolet light A phototherapy is a therapeutic option. It displayed significant benefit in a systematic review and meta-analysis of 19 studies comparing it to methotrexate, although the results with methotrexate were deemed superior (Semin Arthritis Rheum. 2018 Dec;48[3]:495-503).

The pros and cons of getting a baseline brain MRI

Children with localized scleroderma have increased rates of severe headache, peripheral neuropathy, complex partial seizures, and stroke. So it had been Dr. Stevens’ routine practice to obtain an initial brain MRI at the time of diagnosis. Of late, though, she has reconsidered that practice.

“The problem is that some patients with abnormal MRI lesions have no CNS disease at all, and there are also a fair number of patients with a normal MRI who have CNS symptoms. So in our practice we’re pulling back on doing screening MRIs because we don’t know what to do with the findings, and it just makes everybody worried,” she said.

However, if a child with localized scleroderma develops headaches, seizures, neuropathies, or other CNS symptoms, then by all means get an MRI, and if it shows findings such as brain atrophy, white matter lesions, calcifications, or leptomeningeal enhancement, consider treatment, she added.

Dr. Stevens reported receiving research funding from Kineta and Seattle Genetics.

bjancin@mdedge.com

MAUI, HAWAII – One of the most important steps to take when a child has received a biopsy-confirmed diagnosis of localized scleroderma is to sit down with the family and explain the rationale for the aggressive therapies to come, Anne M. Stevens, MD, PhD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

It can be a tough sell at first, especially when a child has only a small red streak on the nose and perhaps a subtle linear lesion on the forehead or scalp. But the family has to come to understand that this is a serious, chronic, progressive fibrotic disease.

“Talk about what a big impact this disease can have on growth of a limb and the normal life of a child because of the cosmetic appearance. Explain that the length of treatment course is based on the long-term outcomes and quality of life. This discussion is usually sufficient” to convince people to give their children “these pretty serious medications,” said Dr. Stevens, professor of pediatrics and head of the division of pediatric rheumatology at the University of Washington, Seattle.

“The treatment goal is to control inflammation and prevent damage in these patients, who we like to catch very early, when it’s a subtle lesion,” she added.
 

The biggest problem

The biggest contributors to poor quality of life in patients with juvenile localized scleroderma are the extracutaneous manifestations, which occur in up to 50% of cases. Joint pain occurs in roughly 20% of patients, joint contractures due to fibrosis of skin and/or tendons in 30%, and myalgia with or without myositis in 15%. Muscle atrophy due to the deep component of the scleroderma can occur. Moreover, growth problems – especially leg or arm length discrepancies – happen in about 20% of patients in prospective studies. These growth problems may not be obvious until a child enters a growth spurt, at which point there is a limited ability to achieve improvement. That’s why Dr. Stevens recommends that every child with localized scleroderma should get a full joint exam at every visit, with measurement and photos of lesions and recording of all erythematous, violaceous, and waxy-hued areas. And if there are lesions on the head, annual eye exams are warranted.

The prevalence of juvenile localized scleroderma in the United States is about 3 per 100,000, with a mean age of onset of 8.2 years. That makes it 100-fold more common than pediatric systemic sclerosis.
 

The treatment ladder

There are no Food and Drug Administration–approved medications for localized scleroderma in children. It’s all off label. That being said, there is strong consensus among members of the Childhood Arthritis and Rheumatology Research Alliance that the first-line therapy is methotrexate at 15 mg/m² or a maximum of 20 mg/week plus intravenous corticosteroids weaned over the course of 3-6 months. This is the treatment regimen with the best supporting evidence of safety and efficacy, including a single Italian randomized, double-blind, placebo-controlled clinical trial (Arthritis Rheum. 2011 Jul;63[7]:1998-2006) and an accompanying long-term, open-label follow-up study (J Am Acad Dermatol. 2012 Dec;67[6]:1151-6).

All of the other treatments she uses for juvenile localized scleroderma – mycophenolate mofetil (CellCept), abatacept (Orencia), tocilizumab (Actemra), and occasionally others – are backed only by a smattering of small case series. However, given the serious potential trajectory of this disease, that modest evidence base has been sufficient for her to receive insurance coverage approval of these agents.

In the randomized trial of first-line methotrexate, 48 of 65 patients treated with methotrexate plus steroid (74%) were responders. And among those 48 responders, 35 (73%) maintained a clinical remission for a mean of 25 months off-drug, while another 13 (27%) were in clinical remission on methotrexate. Twenty-eight patients developed side effects that were generally mild; no one required treatment discontinuation. At the 5-year mark, after an average of an initial 2 years on methotrexate, half of the patients were in a sustained clinical remission, which Dr. Stevens deemed “pretty good” considering the well established and manageable safety profile of the drug.

If a patient fails to respond to methotrexate plus corticosteroids within a few months or later experiences disease progression, Dr. Stevens’ second-line therapy is mycophenolate mofetil in conjunction with corticosteroids. Its use in arresting juvenile localized scleroderma is supported by two favorable published case series, the largest of which includes 10 patients (Rheumatology [Oxford]. 2009 Nov;48[11]:1410-3).

Dr. Stevens’ third-line therapy is intravenous abatacept at 10 mg/kg monthly along with intravenous methylprednisolone at 500 mg/week. There are five published case series, the most recent and largest of which included 13 adult patients, two of whom had en coup de sabre lesions (Acta Derm Venereol. 2018 Apr 16;98[4]:465-6). The biologic also shows promise in patients with advanced severe disease with deep tissue involvement (Semin Arthritis Rheum. 2017 Jun;46[6]:775-81). And abatacept has a plausible mechanism of action in localized scleroderma: French investigators have shown it induces regression of skin fibrosis in a mouse model of the disease (Ann Rheum Dis. 2016 Dec;75[12]:2142-9).

Her fourth-line strategy is the anti-interleukin-6 agent tocilizumab, again in conjunction with corticosteroids. In a translational study, tocilizumab has been shown to normalize dermal fibroblasts and collagen in patients with systemic sclerosis (Ann Rheum Dis. 2018 Sep;77[9]:1362-71). And there have been two promising small retrospective case series as well. A more definitive clinical trial is planned.

Dr. Stevens said that when starting a biologic agent in a child with localized scleroderma, she routinely adds methotrexate until the disease is under control.

Drugs supported by case reports and worth considering on an individual basis as a last resort are hydroxychloroquine, azathioprine, cyclosporine, and imatinib mesylate (Gleevec).

For mild, superficial lesions that don’t cross joints, ultraviolet light A phototherapy is a therapeutic option. It displayed significant benefit in a systematic review and meta-analysis of 19 studies comparing it to methotrexate, although the results with methotrexate were deemed superior (Semin Arthritis Rheum. 2018 Dec;48[3]:495-503).

The pros and cons of getting a baseline brain MRI

Children with localized scleroderma have increased rates of severe headache, peripheral neuropathy, complex partial seizures, and stroke. So it had been Dr. Stevens’ routine practice to obtain an initial brain MRI at the time of diagnosis. Of late, though, she has reconsidered that practice.

“The problem is that some patients with abnormal MRI lesions have no CNS disease at all, and there are also a fair number of patients with a normal MRI who have CNS symptoms. So in our practice we’re pulling back on doing screening MRIs because we don’t know what to do with the findings, and it just makes everybody worried,” she said.

However, if a child with localized scleroderma develops headaches, seizures, neuropathies, or other CNS symptoms, then by all means get an MRI, and if it shows findings such as brain atrophy, white matter lesions, calcifications, or leptomeningeal enhancement, consider treatment, she added.

Dr. Stevens reported receiving research funding from Kineta and Seattle Genetics.

bjancin@mdedge.com

The use of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) as upfront treatment in patients with diffuse large B-cell lymphoma (DLBCL) showed greater toxicity and did not improve progression-free survival versus standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), according to results from a phase 3 trial.

Nephron/Wikimedia Commons/CC BY-SA 3.0

“Less favorable outcomes for patients with recurrent DLBCL prompted efforts to improve first-line approaches and biomarkers to identify high-risk patients,” wrote Nancy L. Bartlett, MD, of Washington University, St. Louis, and her colleagues wrote in the Journal of Clinical Oncology.

The Alliance/CALGB 50303 study included 491 patients with DLBCL who were randomized in a 1:1 fashion to receive DA-EPOCH-R or R-CHOP every 21 days for a total of six cycles. Dosing for the DA-EPOCH-R regimen was determined using absolute neutrophil and platelet counts.

The primary endpoint measured was progression-free survival (PFS); secondary endpoints included safety, overall survival (OS), and response rate.

After a median follow-up of 5.2 years, the researchers found no significant difference in PFS between the study arms (DA-EPOCH-R hazard ratio, 0.93; 95% confidence interval, 0.68-1.27; P = .65). Additionally, there was no significant difference in OS (HR, 1.09; 95% CI, 0.75-1.59; P = .64).

The overall response rate was 88.0% in the R-CHOP arm versus 86.7% in the DA-EPOCH-R arm (P = .67).

With respect to safety, grade 3 or 4 adverse events were more frequently seen in the DA-EPOCH-R group than in the R-CHOP group (P less than .001). These toxicities included febrile neutropenia, infections, neuropathy, and mucositis.

The researchers did see significantly improved PFS in the DA-EPOCH-R arm in post hoc subset analyses of patients with International Prognostic Index (IPI) 3-5, but the subset analysis “was unplanned and not powered” and the significance “must be tempered in light of multiple comparisons.”

“We now understand DLBCL is even more heterogeneous than appreciated when this trial was designed,” the researchers wrote. “Therefore, the National Clinical Trials Network is planning a precision medicine approach to identify molecular subsets of DLBCL and determine if specific chemotherapy platforms and/or targeted agents offer differential benefit.”

The study was supported by the National Cancer Institute. The authors reported financial relationships with Bristol-Myers Squibb, Celgene, Janssen, Jazz Pharmaceuticals, Morphosys, and other companies.

SOURCE: Bartlett NL et al. J Clin Oncol. 2019 Apr 2. doi: 10.1200/JCO.18.01994.

The use of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) as upfront treatment in patients with diffuse large B-cell lymphoma (DLBCL) showed greater toxicity and did not improve progression-free survival versus standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), according to results from a phase 3 trial.

Nephron/Wikimedia Commons/CC BY-SA 3.0

“Less favorable outcomes for patients with recurrent DLBCL prompted efforts to improve first-line approaches and biomarkers to identify high-risk patients,” wrote Nancy L. Bartlett, MD, of Washington University, St. Louis, and her colleagues wrote in the Journal of Clinical Oncology.

The Alliance/CALGB 50303 study included 491 patients with DLBCL who were randomized in a 1:1 fashion to receive DA-EPOCH-R or R-CHOP every 21 days for a total of six cycles. Dosing for the DA-EPOCH-R regimen was determined using absolute neutrophil and platelet counts.

The primary endpoint measured was progression-free survival (PFS); secondary endpoints included safety, overall survival (OS), and response rate.

After a median follow-up of 5.2 years, the researchers found no significant difference in PFS between the study arms (DA-EPOCH-R hazard ratio, 0.93; 95% confidence interval, 0.68-1.27; P = .65). Additionally, there was no significant difference in OS (HR, 1.09; 95% CI, 0.75-1.59; P = .64).

The overall response rate was 88.0% in the R-CHOP arm versus 86.7% in the DA-EPOCH-R arm (P = .67).

With respect to safety, grade 3 or 4 adverse events were more frequently seen in the DA-EPOCH-R group than in the R-CHOP group (P less than .001). These toxicities included febrile neutropenia, infections, neuropathy, and mucositis.

The researchers did see significantly improved PFS in the DA-EPOCH-R arm in post hoc subset analyses of patients with International Prognostic Index (IPI) 3-5, but the subset analysis “was unplanned and not powered” and the significance “must be tempered in light of multiple comparisons.”

“We now understand DLBCL is even more heterogeneous than appreciated when this trial was designed,” the researchers wrote. “Therefore, the National Clinical Trials Network is planning a precision medicine approach to identify molecular subsets of DLBCL and determine if specific chemotherapy platforms and/or targeted agents offer differential benefit.”

The study was supported by the National Cancer Institute. The authors reported financial relationships with Bristol-Myers Squibb, Celgene, Janssen, Jazz Pharmaceuticals, Morphosys, and other companies.

SOURCE: Bartlett NL et al. J Clin Oncol. 2019 Apr 2. doi: 10.1200/JCO.18.01994.

The use of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) as upfront treatment in patients with diffuse large B-cell lymphoma (DLBCL) showed greater toxicity and did not improve progression-free survival versus standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), according to results from a phase 3 trial.

Nephron/Wikimedia Commons/CC BY-SA 3.0

“Less favorable outcomes for patients with recurrent DLBCL prompted efforts to improve first-line approaches and biomarkers to identify high-risk patients,” wrote Nancy L. Bartlett, MD, of Washington University, St. Louis, and her colleagues wrote in the Journal of Clinical Oncology.

The Alliance/CALGB 50303 study included 491 patients with DLBCL who were randomized in a 1:1 fashion to receive DA-EPOCH-R or R-CHOP every 21 days for a total of six cycles. Dosing for the DA-EPOCH-R regimen was determined using absolute neutrophil and platelet counts.

The primary endpoint measured was progression-free survival (PFS); secondary endpoints included safety, overall survival (OS), and response rate.

After a median follow-up of 5.2 years, the researchers found no significant difference in PFS between the study arms (DA-EPOCH-R hazard ratio, 0.93; 95% confidence interval, 0.68-1.27; P = .65). Additionally, there was no significant difference in OS (HR, 1.09; 95% CI, 0.75-1.59; P = .64).

The overall response rate was 88.0% in the R-CHOP arm versus 86.7% in the DA-EPOCH-R arm (P = .67).

With respect to safety, grade 3 or 4 adverse events were more frequently seen in the DA-EPOCH-R group than in the R-CHOP group (P less than .001). These toxicities included febrile neutropenia, infections, neuropathy, and mucositis.

The researchers did see significantly improved PFS in the DA-EPOCH-R arm in post hoc subset analyses of patients with International Prognostic Index (IPI) 3-5, but the subset analysis “was unplanned and not powered” and the significance “must be tempered in light of multiple comparisons.”

“We now understand DLBCL is even more heterogeneous than appreciated when this trial was designed,” the researchers wrote. “Therefore, the National Clinical Trials Network is planning a precision medicine approach to identify molecular subsets of DLBCL and determine if specific chemotherapy platforms and/or targeted agents offer differential benefit.”

The study was supported by the National Cancer Institute. The authors reported financial relationships with Bristol-Myers Squibb, Celgene, Janssen, Jazz Pharmaceuticals, Morphosys, and other companies.

SOURCE: Bartlett NL et al. J Clin Oncol. 2019 Apr 2. doi: 10.1200/JCO.18.01994.

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

On car trips with our kids, we used to listen to comedy tapes. (Cassette tapes. Look them up.) One of our favorite comics was Steven Wright, who made it to the Tonight Show with Johnny Carson. (Google him.)

Wright’s offbeat humor was quirky and a bit philosophical, and was delivered in a deadpan, mumbled monotone. For instance:

When I got to school, the teacher said, “The socks you’re wearing don’t match. They’re two different colors.”

I said, “I go by thickness.”

That punchline goes pop in your head, like a shy little firecracker: How come it never occurred to me to look at it that way?

I thought of Steven Wright recently while I was enrolling Stacy, a 20-year-old, in the iPledge program for a planned course of isotretinoin. Stacy told me she is sexually active and has an IUD.

“When you start the medicine next month,” I told her, “you’ll need to pick a second form of contraception.”

Stacy looked bewildered. When I’ve made that statement to a thousand previous patients, none of them ever looked bewildered.

“I mean,” I said, “besides the IUD, you’ll need to use a second type of contraception, to be sure you don’t get pregnant. You could choose condoms, or one of the other types listed in the booklet I gave you.”

That didn’t seem to help. Stacey hemmed a bit. “Does that mean I have to tell you ... ?”

“Yes, you have to pick another form of birth control and tell me which one it is.”

“I have to tell you every time?”

My go-by-thickness moment – I finally got it. “NO,” I said. “You do NOT have to tell me which second contraceptive you use every time you have sex!”

Steven Wright would be proud of Stacy. Isotretinoin came out in 1982, but nobody ever thought of “choose a second type of contraception” that way before. Stacy goes by retail.

That case reminded of another out-of-left field question I heard for the first – and only – time almost 40 years ago. I had prescribed a cream for a young man.

“Can I get it refilled?” he asked.

“Sure,” I said.

“How do I refill it?” he asked.

“You take it back to the pharmacy, and they refill it for you,” I said.

“But how do they refill it?”

“You show them what you need, and they refill it.”

“But how?”

“Why do you keep asking me that?”

“The tube is going to be all scrunched up from my squeezing it,” he said. “How do they get the new cream back in?”

Well son of a gun, “refill” could mean that, couldn’t it? If you go by thickness.

In idle moments I like to let novel perspectives such as those roll around in my head. The other day I accompanied a relative to an emergency department. While waiting in triage for 5 hours, I looked up and saw a sign on the wall, in big, blue letters: “Support ED Research!”

That puzzled me. I know it can be an important problem, but why the dickens would someone come to an emergency department for erectile dysfunction?

I go by acronyms.
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@mdedge.com.

Favorable results from a phase 2 trial have prompted further development of polatuzumab vedotin in non-Hodgkin lymphoma.

In the ROMULUS trial, polatuzumab vedotin plus rituximab (R-pola) produced more durable responses than did pinatuzumab vedotin plus rituximab (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL).

Researchers also observed a more favorable benefit-risk profile with R-pola.

Franck Morschhauser, MD, of Centre Hospitalier Régional Universitaire de Lille, France, and his colleagues described these findings in the Lancet Haematology.

The ROMULUS trial included 81 DLBCL patients and 42 FL patients. They were randomized to receive R-pola or R-pina (rituximab at 375 mg/m² plus either antibody-drug conjugate at 2.4 mg/kg) every 21 days until disease progression or unacceptable toxicity for up to 1 year.

Among DLBCL patients, the median age was 69 years in the R-pina arm and 68 years in the R-pola arm. Among FL patients, the median age was 59 years in the R-pina arm and 67 years in the R-pola arm.

Seventy-six percent of DLBCL patients randomized to R-pina were refractory to their last treatment, as were 80% of DLBCL patients assigned to R-pola, 52% of FL patients assigned to R-pina, and 35% of FL patients assigned to R-pola.

The median number of prior systemic therapies was three in the R-pina DLBCL arm, the R-pola DLBCL arm, and the R-pina FL arm. The median number of prior therapies was two in the R-pola FL arm.

Response and survival

Among the DLBCL patients, R-pina produced an objective response rate (ORR) of 60% and a complete response (CR) rate of 26%. R-pola produced an ORR of 54% and a CR rate of 21%. The median duration of response was 6.2 months in the R-pina arm and 13.4 months in the R-pola arm.

The median progression-free survival in the DLBCL cohort was 5.4 months for the R-pina arm and 5.6 months for the R-pola arm. The median overall survival was 16.5 months and 20.1 months, respectively.

In the FL cohort, R-pina produced an ORR of 62% and a CR rate of 5%. R-pola produced an ORR of 70% and a CR rate of 45%. The median duration of response was 6.5 months in the R-pina arm and 9.4 months in the R-pola arm.

The median progression-free survival in the FL cohort was 12.7 months for the R-pina arm and 15.3 months for the R-pola arm. The 2-year overall survival rate was 90.5% and 87.8%, respectively. The median overall survival was not reached in either arm.

“Patients treated with R-pola tended to have longer durations of response than those receiving R-pina (particularly those with relapsed or refractory diffuse large B-cell lymphoma), and the results for R-pola compared favorably with other novel antilymphoma agents,” Dr. Morschhauser and his colleagues wrote.

Safety

Among DLBCL patients, serious adverse events (AEs) occurred in 50.0% of those in the R-pina arm and 35.9% of those in the R-pola arm. Among FL patients, serious AEs occurred in 28.6% of those the R-pina arm and 35.0% of those in the R-pola arm.

Ten grade 5 AEs occurred in nine DLBCL patients who received R-pina (21.4%). These events included two cases of sepsis, influenza and pneumonia in the same patient, general physical health deterioration including one death attributed to disease progression, and one case each of Clostridium difficile sepsis, respiratory failure, urosepsis, and sudden death.

There was one grade 5 AE in a FL patient who received R-pola. The 84-year-old patient died of pulmonary congestion 64 days after the last of 12 cycles of treatment.

There were no fatal AEs in the other arms.

“These findings make pola a promising novel candidate for further clinical evaluation in combination regimens in treatment-refractory patients and also in a first-line setting in B-cell non-Hodgkin lymphoma,” Dr. Morschhauser and his colleagues wrote.

Polatuzumab vedotin was chosen by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response, compared with pinatuzumab vedotin.

Polatuzumab vedotin is currently under investigation in the phase 3 POLARIX study. The drug is being combined with rituximab, cyclophosphamide, doxorubicin, and prednisone and compared to rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL.

The ROMULUS study was funded by F Hoffmann-La Roche. The study authors reported relationships with Roche and other companies.

jensmith@mdedge.com

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Mar 29. doi: 10.1016/S2352-3026(19)30026-2.

Favorable results from a phase 2 trial have prompted further development of polatuzumab vedotin in non-Hodgkin lymphoma.

In the ROMULUS trial, polatuzumab vedotin plus rituximab (R-pola) produced more durable responses than did pinatuzumab vedotin plus rituximab (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL).

Researchers also observed a more favorable benefit-risk profile with R-pola.

Franck Morschhauser, MD, of Centre Hospitalier Régional Universitaire de Lille, France, and his colleagues described these findings in the Lancet Haematology.

The ROMULUS trial included 81 DLBCL patients and 42 FL patients. They were randomized to receive R-pola or R-pina (rituximab at 375 mg/m² plus either antibody-drug conjugate at 2.4 mg/kg) every 21 days until disease progression or unacceptable toxicity for up to 1 year.

Among DLBCL patients, the median age was 69 years in the R-pina arm and 68 years in the R-pola arm. Among FL patients, the median age was 59 years in the R-pina arm and 67 years in the R-pola arm.

Seventy-six percent of DLBCL patients randomized to R-pina were refractory to their last treatment, as were 80% of DLBCL patients assigned to R-pola, 52% of FL patients assigned to R-pina, and 35% of FL patients assigned to R-pola.

The median number of prior systemic therapies was three in the R-pina DLBCL arm, the R-pola DLBCL arm, and the R-pina FL arm. The median number of prior therapies was two in the R-pola FL arm.

Response and survival

Among the DLBCL patients, R-pina produced an objective response rate (ORR) of 60% and a complete response (CR) rate of 26%. R-pola produced an ORR of 54% and a CR rate of 21%. The median duration of response was 6.2 months in the R-pina arm and 13.4 months in the R-pola arm.

The median progression-free survival in the DLBCL cohort was 5.4 months for the R-pina arm and 5.6 months for the R-pola arm. The median overall survival was 16.5 months and 20.1 months, respectively.

In the FL cohort, R-pina produced an ORR of 62% and a CR rate of 5%. R-pola produced an ORR of 70% and a CR rate of 45%. The median duration of response was 6.5 months in the R-pina arm and 9.4 months in the R-pola arm.

The median progression-free survival in the FL cohort was 12.7 months for the R-pina arm and 15.3 months for the R-pola arm. The 2-year overall survival rate was 90.5% and 87.8%, respectively. The median overall survival was not reached in either arm.

“Patients treated with R-pola tended to have longer durations of response than those receiving R-pina (particularly those with relapsed or refractory diffuse large B-cell lymphoma), and the results for R-pola compared favorably with other novel antilymphoma agents,” Dr. Morschhauser and his colleagues wrote.

Safety

Among DLBCL patients, serious adverse events (AEs) occurred in 50.0% of those in the R-pina arm and 35.9% of those in the R-pola arm. Among FL patients, serious AEs occurred in 28.6% of those the R-pina arm and 35.0% of those in the R-pola arm.

Ten grade 5 AEs occurred in nine DLBCL patients who received R-pina (21.4%). These events included two cases of sepsis, influenza and pneumonia in the same patient, general physical health deterioration including one death attributed to disease progression, and one case each of Clostridium difficile sepsis, respiratory failure, urosepsis, and sudden death.

There was one grade 5 AE in a FL patient who received R-pola. The 84-year-old patient died of pulmonary congestion 64 days after the last of 12 cycles of treatment.

There were no fatal AEs in the other arms.

“These findings make pola a promising novel candidate for further clinical evaluation in combination regimens in treatment-refractory patients and also in a first-line setting in B-cell non-Hodgkin lymphoma,” Dr. Morschhauser and his colleagues wrote.

Polatuzumab vedotin was chosen by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response, compared with pinatuzumab vedotin.

Polatuzumab vedotin is currently under investigation in the phase 3 POLARIX study. The drug is being combined with rituximab, cyclophosphamide, doxorubicin, and prednisone and compared to rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL.

The ROMULUS study was funded by F Hoffmann-La Roche. The study authors reported relationships with Roche and other companies.

jensmith@mdedge.com

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Mar 29. doi: 10.1016/S2352-3026(19)30026-2.

Favorable results from a phase 2 trial have prompted further development of polatuzumab vedotin in non-Hodgkin lymphoma.

In the ROMULUS trial, polatuzumab vedotin plus rituximab (R-pola) produced more durable responses than did pinatuzumab vedotin plus rituximab (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL).

Researchers also observed a more favorable benefit-risk profile with R-pola.

Franck Morschhauser, MD, of Centre Hospitalier Régional Universitaire de Lille, France, and his colleagues described these findings in the Lancet Haematology.

The ROMULUS trial included 81 DLBCL patients and 42 FL patients. They were randomized to receive R-pola or R-pina (rituximab at 375 mg/m² plus either antibody-drug conjugate at 2.4 mg/kg) every 21 days until disease progression or unacceptable toxicity for up to 1 year.

Among DLBCL patients, the median age was 69 years in the R-pina arm and 68 years in the R-pola arm. Among FL patients, the median age was 59 years in the R-pina arm and 67 years in the R-pola arm.

Seventy-six percent of DLBCL patients randomized to R-pina were refractory to their last treatment, as were 80% of DLBCL patients assigned to R-pola, 52% of FL patients assigned to R-pina, and 35% of FL patients assigned to R-pola.

The median number of prior systemic therapies was three in the R-pina DLBCL arm, the R-pola DLBCL arm, and the R-pina FL arm. The median number of prior therapies was two in the R-pola FL arm.

Response and survival

Among the DLBCL patients, R-pina produced an objective response rate (ORR) of 60% and a complete response (CR) rate of 26%. R-pola produced an ORR of 54% and a CR rate of 21%. The median duration of response was 6.2 months in the R-pina arm and 13.4 months in the R-pola arm.

The median progression-free survival in the DLBCL cohort was 5.4 months for the R-pina arm and 5.6 months for the R-pola arm. The median overall survival was 16.5 months and 20.1 months, respectively.

In the FL cohort, R-pina produced an ORR of 62% and a CR rate of 5%. R-pola produced an ORR of 70% and a CR rate of 45%. The median duration of response was 6.5 months in the R-pina arm and 9.4 months in the R-pola arm.

The median progression-free survival in the FL cohort was 12.7 months for the R-pina arm and 15.3 months for the R-pola arm. The 2-year overall survival rate was 90.5% and 87.8%, respectively. The median overall survival was not reached in either arm.

“Patients treated with R-pola tended to have longer durations of response than those receiving R-pina (particularly those with relapsed or refractory diffuse large B-cell lymphoma), and the results for R-pola compared favorably with other novel antilymphoma agents,” Dr. Morschhauser and his colleagues wrote.

Safety

Among DLBCL patients, serious adverse events (AEs) occurred in 50.0% of those in the R-pina arm and 35.9% of those in the R-pola arm. Among FL patients, serious AEs occurred in 28.6% of those the R-pina arm and 35.0% of those in the R-pola arm.

Ten grade 5 AEs occurred in nine DLBCL patients who received R-pina (21.4%). These events included two cases of sepsis, influenza and pneumonia in the same patient, general physical health deterioration including one death attributed to disease progression, and one case each of Clostridium difficile sepsis, respiratory failure, urosepsis, and sudden death.

There was one grade 5 AE in a FL patient who received R-pola. The 84-year-old patient died of pulmonary congestion 64 days after the last of 12 cycles of treatment.

There were no fatal AEs in the other arms.

“These findings make pola a promising novel candidate for further clinical evaluation in combination regimens in treatment-refractory patients and also in a first-line setting in B-cell non-Hodgkin lymphoma,” Dr. Morschhauser and his colleagues wrote.

Polatuzumab vedotin was chosen by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response, compared with pinatuzumab vedotin.

Polatuzumab vedotin is currently under investigation in the phase 3 POLARIX study. The drug is being combined with rituximab, cyclophosphamide, doxorubicin, and prednisone and compared to rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL.

The ROMULUS study was funded by F Hoffmann-La Roche. The study authors reported relationships with Roche and other companies.

jensmith@mdedge.com

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Mar 29. doi: 10.1016/S2352-3026(19)30026-2.

An ingestible electronic capsule that measures intestinal gas. A talented toilet. Obesity subtype biomarkers, improved endoscopies, and an IBD wellness app. Could any of these five innovations transform medicine and lead to gastrointestinal glory?

Five companies will present their innovations to a panel of experts at this week's AGA Tech Summit Shark Tank event, brought to you by the AGA Center for GI Innovation and Technology. Stay tuned to GI & Hepatology News for the AGA Tech Summit Report, where we will provide more information on each product and announce the winner as decided by a panel of judges and the AGA Tech Summit audience. But first, check out the contestants and their products:

1. TrueLoo: Excreta-examining toilet

“TrueLoo is a replacement for a conventional toilet seat,” said Vikram Kashyap, CEO of Toi Labs. “The device acquires time-lapse images of a bowel movement or urination event automatically and under controlled conditions. These images are transmitted to a remote cloud server and analyzed to measure various properties related to the toilet event.”

According to Mr. Kashyap, the firm is developing a way to conduct fecal occult blood tests on the platform without requiring contact or direct sample handling.

2. Ultivision: Video endoscopy booster

“The Ultivision technology will be integrated seamlessly into the endoscopy workflow and provide feedback in real-time,” said University of California at Irvine gastroenterologist Jason B. Samarasena, MD, cofounder of DocBot. “As the endoscopist is performing the upper endoscopy, a lag-free video overlay will display boxes over suspicious lesions that the endoscopist should draw their attention to. When the area is more closely examined, the algorithm will deliver a prediction as to the likelihood that this tissue harbors dysplasia.”



3. Pheno Test: Know your obesity subtype

The Pheno Test aims to unveil obesity biomarkers which “are supported by a diagnostic algorithm... which has already been validated to predict weight response to obesity pharmacotherapy,” said Phenomix Sciences CEO Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic.

According to Dr. Acosta, a separate trial tracked patients with obesity, including some who were treated differently based on their phenotype. Those patients lost more than double their body weight compared with those who received standard of care and had fewer adverse effects linked to treatment.
 

4. Oshi: Meet the “all in one” IBD app

The Oshi app, which is now available for Apple iOS and Android, allows patients with IBD to track their symptoms and “uncover hidden patterns affecting wellness,” said Dan Weinstein, MBA, CEO of Oshi Health.

Patients can also read about IBD news, hear from other patients about their experiences, and ask questions of health professionals. “We are expanding to include proven digital tools to enhance IBD care such as medication adherence, treatment history logs, at-home fecal calprotectin testing, and more,” Mr. Weinstein said.
 

5. Atmo Gas Capsule: Swallow your way to GI insights

An ingestible electronic capsule the size of a large vitamin tablet gathers “digital health data in the form of gas concentrations as it passes through the gut for the screening and diagnosis of gastrointestinal disorders and for assessing effects of dietary treatments on the gut,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences.

The capsule transmits data to a small receiver and on to a smartphone, Mr. Hebblewhite said. “The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud.”

An ingestible electronic capsule that measures intestinal gas. A talented toilet. Obesity subtype biomarkers, improved endoscopies, and an IBD wellness app. Could any of these five innovations transform medicine and lead to gastrointestinal glory?

Five companies will present their innovations to a panel of experts at this week's AGA Tech Summit Shark Tank event, brought to you by the AGA Center for GI Innovation and Technology. Stay tuned to GI & Hepatology News for the AGA Tech Summit Report, where we will provide more information on each product and announce the winner as decided by a panel of judges and the AGA Tech Summit audience. But first, check out the contestants and their products:

1. TrueLoo: Excreta-examining toilet

“TrueLoo is a replacement for a conventional toilet seat,” said Vikram Kashyap, CEO of Toi Labs. “The device acquires time-lapse images of a bowel movement or urination event automatically and under controlled conditions. These images are transmitted to a remote cloud server and analyzed to measure various properties related to the toilet event.”

According to Mr. Kashyap, the firm is developing a way to conduct fecal occult blood tests on the platform without requiring contact or direct sample handling.

2. Ultivision: Video endoscopy booster

“The Ultivision technology will be integrated seamlessly into the endoscopy workflow and provide feedback in real-time,” said University of California at Irvine gastroenterologist Jason B. Samarasena, MD, cofounder of DocBot. “As the endoscopist is performing the upper endoscopy, a lag-free video overlay will display boxes over suspicious lesions that the endoscopist should draw their attention to. When the area is more closely examined, the algorithm will deliver a prediction as to the likelihood that this tissue harbors dysplasia.”



3. Pheno Test: Know your obesity subtype

The Pheno Test aims to unveil obesity biomarkers which “are supported by a diagnostic algorithm... which has already been validated to predict weight response to obesity pharmacotherapy,” said Phenomix Sciences CEO Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic.

According to Dr. Acosta, a separate trial tracked patients with obesity, including some who were treated differently based on their phenotype. Those patients lost more than double their body weight compared with those who received standard of care and had fewer adverse effects linked to treatment.
 

4. Oshi: Meet the “all in one” IBD app

The Oshi app, which is now available for Apple iOS and Android, allows patients with IBD to track their symptoms and “uncover hidden patterns affecting wellness,” said Dan Weinstein, MBA, CEO of Oshi Health.

Patients can also read about IBD news, hear from other patients about their experiences, and ask questions of health professionals. “We are expanding to include proven digital tools to enhance IBD care such as medication adherence, treatment history logs, at-home fecal calprotectin testing, and more,” Mr. Weinstein said.
 

5. Atmo Gas Capsule: Swallow your way to GI insights

An ingestible electronic capsule the size of a large vitamin tablet gathers “digital health data in the form of gas concentrations as it passes through the gut for the screening and diagnosis of gastrointestinal disorders and for assessing effects of dietary treatments on the gut,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences.

The capsule transmits data to a small receiver and on to a smartphone, Mr. Hebblewhite said. “The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud.”

An ingestible electronic capsule that measures intestinal gas. A talented toilet. Obesity subtype biomarkers, improved endoscopies, and an IBD wellness app. Could any of these five innovations transform medicine and lead to gastrointestinal glory?

Five companies will present their innovations to a panel of experts at this week's AGA Tech Summit Shark Tank event, brought to you by the AGA Center for GI Innovation and Technology. Stay tuned to GI & Hepatology News for the AGA Tech Summit Report, where we will provide more information on each product and announce the winner as decided by a panel of judges and the AGA Tech Summit audience. But first, check out the contestants and their products:

1. TrueLoo: Excreta-examining toilet

“TrueLoo is a replacement for a conventional toilet seat,” said Vikram Kashyap, CEO of Toi Labs. “The device acquires time-lapse images of a bowel movement or urination event automatically and under controlled conditions. These images are transmitted to a remote cloud server and analyzed to measure various properties related to the toilet event.”

According to Mr. Kashyap, the firm is developing a way to conduct fecal occult blood tests on the platform without requiring contact or direct sample handling.

2. Ultivision: Video endoscopy booster

“The Ultivision technology will be integrated seamlessly into the endoscopy workflow and provide feedback in real-time,” said University of California at Irvine gastroenterologist Jason B. Samarasena, MD, cofounder of DocBot. “As the endoscopist is performing the upper endoscopy, a lag-free video overlay will display boxes over suspicious lesions that the endoscopist should draw their attention to. When the area is more closely examined, the algorithm will deliver a prediction as to the likelihood that this tissue harbors dysplasia.”



3. Pheno Test: Know your obesity subtype

The Pheno Test aims to unveil obesity biomarkers which “are supported by a diagnostic algorithm... which has already been validated to predict weight response to obesity pharmacotherapy,” said Phenomix Sciences CEO Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic.

According to Dr. Acosta, a separate trial tracked patients with obesity, including some who were treated differently based on their phenotype. Those patients lost more than double their body weight compared with those who received standard of care and had fewer adverse effects linked to treatment.
 

4. Oshi: Meet the “all in one” IBD app

The Oshi app, which is now available for Apple iOS and Android, allows patients with IBD to track their symptoms and “uncover hidden patterns affecting wellness,” said Dan Weinstein, MBA, CEO of Oshi Health.

Patients can also read about IBD news, hear from other patients about their experiences, and ask questions of health professionals. “We are expanding to include proven digital tools to enhance IBD care such as medication adherence, treatment history logs, at-home fecal calprotectin testing, and more,” Mr. Weinstein said.
 

5. Atmo Gas Capsule: Swallow your way to GI insights

An ingestible electronic capsule the size of a large vitamin tablet gathers “digital health data in the form of gas concentrations as it passes through the gut for the screening and diagnosis of gastrointestinal disorders and for assessing effects of dietary treatments on the gut,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences.

The capsule transmits data to a small receiver and on to a smartphone, Mr. Hebblewhite said. “The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud.”

SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.

M. Alexander Otto/MDedge News

The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.

PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.

The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.

The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.

To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.

Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.

Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.

PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.

Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.

Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.

PrEP use was most common among white men who have sex with men and among people under 30 years old.

There was no external funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Misra K et al. 2019 CROI, Abstract 107.

SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.

M. Alexander Otto/MDedge News

The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.

PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.

The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.

The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.

To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.

Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.

Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.

PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.

Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.

Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.

PrEP use was most common among white men who have sex with men and among people under 30 years old.

There was no external funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Misra K et al. 2019 CROI, Abstract 107.

SEATTLE – Almost a third of patients who developed HIV while on pre-exposure prophylaxis (PrEP) had strains that were resistant to emtricitabine – a component of the PrEP medication Truvada along with tenofovir – at time of diagnosis, compared with just 2% of those not on PrEP, in a review of more than 3,500 newly diagnosed HIV cases in New York.

M. Alexander Otto/MDedge News

The finding points to a growing concern as use of PrEP becomes more common: the induction of resistance to HIV treatments.

PrEP is highly effective, so it’s likely that the PrEP patients already had HIV when they started treatment. Nucleic acid amplification testing (NAAT) is the only way to rule it out definitively, but only 5% of PrEP users in the study were screened with NAAT within 2 days of initiation.

The usual test – HIV antibody screening – returns a false negative in the window between HIV exposure and active infection, when antibodies turn positive, which can take months. NAAT, on the other hand, looks for evidence of the virus directly.

The findings led the investigators to urge routine NAAT screening before PrEP, something that New York State guidelines currently recommend only if patients present with symptoms of acute HIV infection or report condomless sex in the previous 4 weeks.

To prevent drug resistance, “rigorous screening that includes NAAT is critical.” It reduces “the likelihood of PrEP start during undetected HIV infection,” said lead investigator Kavita Misra, PhD, MPH, a senior epidemiologist at the New York City Department of Health and Mental Hygiene.

Her team reviewed 3,685 people in New York who were diagnosed with HIV from November 2015 to August 2017; 91 had been on PrEP beforehand for a median of 106 days.

Postdiagnosis genotyping was available for 75% of PrEP users and 63% in the no-PrEP group. Resistance mutations to emtricitabine were significantly more prevalent with PrEP than without (29% versus 2%, respectively; P less than .0001). None of the PrEP users, but four in the no-PrEP group, had resistance to the other component of Truvada, tenofovir.

PrEP users were more likely to be diagnosed with HIV in the acute phase of infection than were those not using PrEP (33% versus 9%; P less than .0001), probably because they were also more likely to have regular office visits while on PrEP.

Skeptics at the Conference on Retroviruses and Opportunistic Infections, where the study was presented, wondered whether emtricitabine resistance would have been more common in the no-PrEP group if the infection had been picked up earlier because resistance fades as the infection progresses.

Dr. Misra said it was a good question and that her team will look into it. However, she stood by her conclusions.

PrEP use was most common among white men who have sex with men and among people under 30 years old.

There was no external funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Misra K et al. 2019 CROI, Abstract 107.

Although the gastroenterology specialty relies heavily on technology, only incremental advances have been made in this space in the last several decades. “While the potential for innovation is huge, we need to overcome structural and conceptual barriers to realize its true potential,” said Pankaj Jay Pasricha, MD, vice chair of the department of medicine at Johns Hopkins University, Baltimore. Dr. Pasricha will discuss what barriers exist and how to overcome them in his keynote presentation at 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Some barriers are risk aversion, reimbursement challenges, and failure to understand true unmet needs. “We need to find practical solutions that are technologically innovative that can get to market,” he said. The general concepts that Dr. Pasricha talks about will be discussed in detail with specific examples during the summit’s sessions.

When looking to bring innovative ideas to market, Dr. Pasricha recommends learning from individuals who have already done this successfully and from those who have tried and failed. One way to do this is to connect with inventors, entrepreneurs, investors, health care providers and institutions, and regulatory and reimbursement stakeholders through the AGA Center for GI Innovation & Technology (CGIT), which he helped found 10 years ago and served as the center's first chair.

The center supports innovation and developing new technology in gastroenterology, hepatology, nutrition, and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process, according to CGIT’s website. It serves as a key resource for industry and physician innovators developing new technology in gastroenterology, and provides guidance to the Food and Drug Administration and other regulatory groups to expedite the device development process.

“CGIT’s purpose is to provide education on how to identify needs, find solutions, and provide roadmaps for connecting ideas and bringing them to the real world,” Dr. Pasricha said. “We need to create disruptive technologies that will address unmet needs at every level from the average gastroenterologist in practice, to advanced endoscopists, and even advanced surgeons who perform gastroenterology procedures.”

CGIT also provides guidance for bringing new technologies into clinical trials through the creation of registries and other means. You can learn more about the center at www.gastro.org/CGIT. 

Regarding recent advances in technologies, Dr. Pasricha said there are now better ways to ablate tissue, do tissue anastomosis, prevent reflux, promote weight loss, and resect locally advanced cancer. “Platform” technologies such as new ways to deliver energy, flexible robotics, and artificial intelligence are also beginning to emerge in our specialty.

Dr. Pasricha is quite experienced in bringing new technologies to market. He holds more than 50 patents that have either been issued or are in process by The United States Patent and Trademark Office and has cofounded several companies within both the medtech/endoscopy and biotech gastroenterology spaces.

His contributions to endoscopy include the use of botulinum toxin for gastroenterology disorders, cryotherapy, novel stents, and the POEM procedure. He is currently working with Galvani Bioelectronics to develop a novel neuromodulation therapy for type 2 diabetes, which has become a worldwide scourge.

Dr. Pasricha discloses being a consultant for several pharmaceutical companies.

Although the gastroenterology specialty relies heavily on technology, only incremental advances have been made in this space in the last several decades. “While the potential for innovation is huge, we need to overcome structural and conceptual barriers to realize its true potential,” said Pankaj Jay Pasricha, MD, vice chair of the department of medicine at Johns Hopkins University, Baltimore. Dr. Pasricha will discuss what barriers exist and how to overcome them in his keynote presentation at 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Some barriers are risk aversion, reimbursement challenges, and failure to understand true unmet needs. “We need to find practical solutions that are technologically innovative that can get to market,” he said. The general concepts that Dr. Pasricha talks about will be discussed in detail with specific examples during the summit’s sessions.

When looking to bring innovative ideas to market, Dr. Pasricha recommends learning from individuals who have already done this successfully and from those who have tried and failed. One way to do this is to connect with inventors, entrepreneurs, investors, health care providers and institutions, and regulatory and reimbursement stakeholders through the AGA Center for GI Innovation & Technology (CGIT), which he helped found 10 years ago and served as the center's first chair.

The center supports innovation and developing new technology in gastroenterology, hepatology, nutrition, and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process, according to CGIT’s website. It serves as a key resource for industry and physician innovators developing new technology in gastroenterology, and provides guidance to the Food and Drug Administration and other regulatory groups to expedite the device development process.

“CGIT’s purpose is to provide education on how to identify needs, find solutions, and provide roadmaps for connecting ideas and bringing them to the real world,” Dr. Pasricha said. “We need to create disruptive technologies that will address unmet needs at every level from the average gastroenterologist in practice, to advanced endoscopists, and even advanced surgeons who perform gastroenterology procedures.”

CGIT also provides guidance for bringing new technologies into clinical trials through the creation of registries and other means. You can learn more about the center at www.gastro.org/CGIT. 

Regarding recent advances in technologies, Dr. Pasricha said there are now better ways to ablate tissue, do tissue anastomosis, prevent reflux, promote weight loss, and resect locally advanced cancer. “Platform” technologies such as new ways to deliver energy, flexible robotics, and artificial intelligence are also beginning to emerge in our specialty.

Dr. Pasricha is quite experienced in bringing new technologies to market. He holds more than 50 patents that have either been issued or are in process by The United States Patent and Trademark Office and has cofounded several companies within both the medtech/endoscopy and biotech gastroenterology spaces.

His contributions to endoscopy include the use of botulinum toxin for gastroenterology disorders, cryotherapy, novel stents, and the POEM procedure. He is currently working with Galvani Bioelectronics to develop a novel neuromodulation therapy for type 2 diabetes, which has become a worldwide scourge.

Dr. Pasricha discloses being a consultant for several pharmaceutical companies.

Although the gastroenterology specialty relies heavily on technology, only incremental advances have been made in this space in the last several decades. “While the potential for innovation is huge, we need to overcome structural and conceptual barriers to realize its true potential,” said Pankaj Jay Pasricha, MD, vice chair of the department of medicine at Johns Hopkins University, Baltimore. Dr. Pasricha will discuss what barriers exist and how to overcome them in his keynote presentation at 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Some barriers are risk aversion, reimbursement challenges, and failure to understand true unmet needs. “We need to find practical solutions that are technologically innovative that can get to market,” he said. The general concepts that Dr. Pasricha talks about will be discussed in detail with specific examples during the summit’s sessions.

When looking to bring innovative ideas to market, Dr. Pasricha recommends learning from individuals who have already done this successfully and from those who have tried and failed. One way to do this is to connect with inventors, entrepreneurs, investors, health care providers and institutions, and regulatory and reimbursement stakeholders through the AGA Center for GI Innovation & Technology (CGIT), which he helped found 10 years ago and served as the center's first chair.

The center supports innovation and developing new technology in gastroenterology, hepatology, nutrition, and obesity by guiding medical device and therapeutics innovators through the technology development and adoption process, according to CGIT’s website. It serves as a key resource for industry and physician innovators developing new technology in gastroenterology, and provides guidance to the Food and Drug Administration and other regulatory groups to expedite the device development process.

“CGIT’s purpose is to provide education on how to identify needs, find solutions, and provide roadmaps for connecting ideas and bringing them to the real world,” Dr. Pasricha said. “We need to create disruptive technologies that will address unmet needs at every level from the average gastroenterologist in practice, to advanced endoscopists, and even advanced surgeons who perform gastroenterology procedures.”

CGIT also provides guidance for bringing new technologies into clinical trials through the creation of registries and other means. You can learn more about the center at www.gastro.org/CGIT. 

Regarding recent advances in technologies, Dr. Pasricha said there are now better ways to ablate tissue, do tissue anastomosis, prevent reflux, promote weight loss, and resect locally advanced cancer. “Platform” technologies such as new ways to deliver energy, flexible robotics, and artificial intelligence are also beginning to emerge in our specialty.

Dr. Pasricha is quite experienced in bringing new technologies to market. He holds more than 50 patents that have either been issued or are in process by The United States Patent and Trademark Office and has cofounded several companies within both the medtech/endoscopy and biotech gastroenterology spaces.

His contributions to endoscopy include the use of botulinum toxin for gastroenterology disorders, cryotherapy, novel stents, and the POEM procedure. He is currently working with Galvani Bioelectronics to develop a novel neuromodulation therapy for type 2 diabetes, which has become a worldwide scourge.

Dr. Pasricha discloses being a consultant for several pharmaceutical companies.

The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.

This marks the first time the FDA has released a list of nitrosamine-free ARBs since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.

Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.

Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.

“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.

The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.

The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.

More information, including the full statement, is available on the FDA’s website.

cpalmer@mdedge.com

The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.

This marks the first time the FDA has released a list of nitrosamine-free ARBs since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.

Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.

Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.

“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.

The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.

The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.

More information, including the full statement, is available on the FDA’s website.

cpalmer@mdedge.com

The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.

This marks the first time the FDA has released a list of nitrosamine-free ARBs since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.

Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.

Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.

“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.

The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.

The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.

More information, including the full statement, is available on the FDA’s website.

cpalmer@mdedge.com

GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.

Will Pass/MDedge News

Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.

This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.

Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.

Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.

All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m² or 500 mg) on day 1, bendamustine 70 mg/m² on days 1 and 2, and cytarabine 500 mg/m² on days 1 through 3, given in a 28-day cycle.

Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.

Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.

Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.

For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).

The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.

The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.

Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”

During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.

“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”

The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.

In an interview, Dr. Rule added perspective to these findings.

“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”

However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.

Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.

He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”

With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.

The investigators reported having no conflicts of interest.
 

GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.

Will Pass/MDedge News

Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.

This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.

Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.

Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.

All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m² or 500 mg) on day 1, bendamustine 70 mg/m² on days 1 and 2, and cytarabine 500 mg/m² on days 1 through 3, given in a 28-day cycle.

Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.

Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.

Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.

For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).

The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.

The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.

Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”

During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.

“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”

The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.

In an interview, Dr. Rule added perspective to these findings.

“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”

However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.

Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.

He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”

With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.

The investigators reported having no conflicts of interest.
 

GLASGOW – Patients with relapsed or refractory mantle cell lymphoma (MCL) who experience disease progression on a Bruton’s tyrosine kinase inhibitor (BTKi) may respond best to a combination of rituximab, bendamustine, and cytarabine (R-BAC), based on early results from an ongoing retrospective study.

Will Pass/MDedge News

Findings from the study, which were presented at the annual meeting of the British Society for Haematology, showed that R-BAC after BTKi failure had an overall response rate (ORR) of 90.5%.

This is a “remarkable response rate” according to the investigators, who cited previously reported response rates for other treatments ranging from 29% to 53%.

Treatment of relapsed/refractory MCL patients in the post-BTKi setting is an area of unmet clinical need, said senior author Simon Rule, MD, of the University of Plymouth, England. He noted that there is currently no consensus regarding best treatment strategy for this patient population.

Dr. Rule said that he and his colleagues have collected data on 30 patients so far, of which 22 were included in this early data release.

All patients received R-BAC between 2016 and 2018 at treatment centers in Italy and the United Kingdom. Treatment consisted of rituximab (375 mg/m² or 500 mg) on day 1, bendamustine 70 mg/m² on days 1 and 2, and cytarabine 500 mg/m² on days 1 through 3, given in a 28-day cycle.

Patients received R-BAC immediately after BTKi failure. Data were drawn from hospital records.

Analysis showed that the median patient age was 65 years, with a range from 43 to 79 years. Most patients were men (81.8%), 55.0% were high risk based on the Mantle Cell Lymphoma International Prognostic Index, and 22.7% had blastoid morphology.

Patients had a median of two prior systemic therapies, with a range from one to six lines. First-line therapies included rituximab in combination with HDAC (high-dose cytarabine containing regimen), CHOP, CVP, or ibrutinib. Nine patients (42.9%) had allogeneic stem cell transplantation (ASCT) after induction treatment.

For BTKi therapy, most patients received ibrutinib (n = 18), while the remainder received acalabrutinib, tirabrutinib or M7583. Most patients discontinued BTKi therapy because of disease progression (90.9%); two patients stopped because of a lack of response (9.1%).

The median number of R-BAC cycles received was four. Two patients started with attenuated doses and seven patients reduced doses after the first cycle. More than 70% of patients completed R-BAC treatment.

The estimated median progression-free survival was 7.3 months and estimated median overall survival was 11.2 months.

Although the investigators reported a complete response rate of 57.1%, they noted that this figure “may be exaggerated” because of a lack of bone marrow biopsy; however, they suggested that the overall response rate (90.5%) “should be accurate.”

During the course of treatment, 31.8% of patients required inpatient admission, 22.7% developed neutropenic fever, and 77.8% required transfusion support. No treatment-related deaths occurred.

“This population, enriched for patients with high risk features, showed remarkable response rates to R-BAC,” the investigators wrote. “The treatment had acceptable toxicity, maintained efficacy at attenuated doses, and was used successfully as a bridge to ASCT in over 20% of patients.”

The investigators suggested that R-BAC should be considered a new standard of care in the United Kingdom for bendamustine-naive patients who are unable to be enrolled in clinical trials. “The high response rate makes it particularly appealing for patients considered candidates for consolidation ASCT,” they wrote.

In an interview, Dr. Rule added perspective to these findings.

“There’s been an obsession with venetoclax, that that’s the answer, but it really isn’t,” Dr. Rule said. “So people are looking for a new drug. I guess what I do differently to most people is I use CHOP frontline rather than bendamustine. To me, that’s the best way of sequencing the therapies, whereas if you use [bendamustine and rituximab] up front, which a lot of people do, particularly in the [United] States, your R-BAC might not be so effective.”

However, Dr. Rule said that first-line therapies appear to have minimal impact on R-BAC efficacy. “Even if you’ve had bendamustine, even if you’ve had high-dose cytarabine, even if you’ve had an allogeneic stem cell transplant, [R-BAC] still works,” he said.

Where patients have issues with tolerability, Dr. Rule noted that dose reductions are possible without sacrificing efficacy.

He offered an example of such a scenario. “My oldest patient was about 80 with blastoid disease, relapsing,” Dr. Rule said. “After ibrutinib, I gave him just a single dose of bendamustine at 70 mg, a single dose of cytarabine at 500 mg, just 1 day, and he had that six times, probably 3 weeks apart. He’s been in complete remission for over a year.”

With data on 30 patients collected, Dr. Rule said that he and his colleagues plan to present more extensive findings at the European Hematology Association Congress, held June 13-16 in Amsterdam.

The investigators reported having no conflicts of interest.
 

Concerns about abatacept (Orencia)-related lung disease in patients with rheumatoid arthritis appear to be unfounded, a large U.S. database review has determined.

designer491/Thinkstock

Safety signals seen in a small subset of patients in the 2006 ASSURE study likely arose from chance, Samy Suissa, PhD, and his colleagues wrote in Seminars in Arthritis & Rheumatism. Patients in that study with preexisting chronic obstructive pulmonary disease (COPD) were 84% more likely to develop an exacerbation or other lung disorder than were those taking a placebo comparator.

The new database study contradicted that finding.

“Our study suggests that these numerical differences in ASSURE are expected results of random variation and thus compatible with chance,” Dr. Suissa of Jewish General Hospital and McGill University, both in Montreal, and his coauthors wrote. “Moreover, our findings are consistent with two studies of the safety of abatacept in the context of interstitial lung disease, albeit a different respiratory disease than COPD.”

The year-long ASSURE trial reported on the safety of abatacept in 959 patients versus 482 assigned to placebo. The safety signal arose in a subgroup of 54 patients with COPD, 37 of whom were assigned to abatacept and 17 to placebo. Among these were four serious respiratory adverse events (COPD exacerbation, worsening of COPD, bronchitis, and pneumonia) in four patients taking abatacept and none in the placebo arm.

“It is useful to note that this difference of 11% versus 0% rate is compatible with chance [exact P = .31], while the exact 95% confidence interval for the odds ratio is wide and includes unity ... The trial also reported more mild-moderate respiratory events with abatacept than with placebo [43.2% vs. 23.5%], including cough, rhonchi, COPD exacerbation, COPD, dyspnea, and nasal congestion. This difference resulted in an odds ration of 1.84,” with a wide confidence interval that included unity (0.48-8.63).

Nevertheless, these findings led to the addition of a warning in the prescribing insert: “Adult COPD patients treated with Orencia developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. Use of Orencia in patients with RA and COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.”

Dr. Suissa’s team used the U.S. MarketScan prescribing database to asses the risk of respiratory adverse events associated with abatacept, compared with other biologic disease-modifying antirheumatic drugs (DMARDs) in a real-world setting.

The cohort comprised 1,807 patients with rheumatoid arthritis and COPD who started a new prescription for abatacept, matched in time to 3,547 who initiated another biologic DMARD. The primary endpoint was the combined risk of hospitalization for COPD exacerbation, bronchitis, and hospitalized pneumonia or influenza.

The most common comparator biologic DMARDs were etanercept, adalimumab, rituximab, and infliximab.

For patients with COPD and comparator patients, the incidence rates for COPD exacerbation were 1.2 per 100 person-years with abatacept and 2.1 per 100 person-years with a different biologic DMARD; for bronchitis, the respective rates were 4.2 and 5.3; for hospitalized pneumonia or influenza, 3.6 and 2.6; and for outpatient pneumonia or flu, 14.7 and 14.4. For the combined endpoint, the incidence rate was 8.7 per 100 person-years with abatacept and 9.9 per 100 person-years with other biologic DMARDs.

The adjusted hazard ratio of the combined endpoint with abatacept versus that with other biologic DMARDs was a nonsignificant risk of 0.87. The hazard ratio with abatacept was 0.60 for hospitalized COPD; 0.80 for bronchitis; 1.39 for hospitalized pneumonia and flu; and 1.05 for outpatient pneumonia and flu. None of these associations was statistically significant.

“One exception was the risk of hospitalization for pneumonia or influenza, which was higher with abatacept among patients with more severe COPD,” at 6.99, than it was with other biologic DMARDs, the authors noted.

Dr. Suissa disclosed relationships with AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Novartis.

msullivan@mdedge.com

SOURCE: Suissa S et al. Semin Arthritis Rheum. 2019 Mar 16. doi: 10.1016j.semarthrit.2019.03.007.
 

Concerns about abatacept (Orencia)-related lung disease in patients with rheumatoid arthritis appear to be unfounded, a large U.S. database review has determined.

designer491/Thinkstock

Safety signals seen in a small subset of patients in the 2006 ASSURE study likely arose from chance, Samy Suissa, PhD, and his colleagues wrote in Seminars in Arthritis & Rheumatism. Patients in that study with preexisting chronic obstructive pulmonary disease (COPD) were 84% more likely to develop an exacerbation or other lung disorder than were those taking a placebo comparator.

The new database study contradicted that finding.

“Our study suggests that these numerical differences in ASSURE are expected results of random variation and thus compatible with chance,” Dr. Suissa of Jewish General Hospital and McGill University, both in Montreal, and his coauthors wrote. “Moreover, our findings are consistent with two studies of the safety of abatacept in the context of interstitial lung disease, albeit a different respiratory disease than COPD.”

The year-long ASSURE trial reported on the safety of abatacept in 959 patients versus 482 assigned to placebo. The safety signal arose in a subgroup of 54 patients with COPD, 37 of whom were assigned to abatacept and 17 to placebo. Among these were four serious respiratory adverse events (COPD exacerbation, worsening of COPD, bronchitis, and pneumonia) in four patients taking abatacept and none in the placebo arm.

“It is useful to note that this difference of 11% versus 0% rate is compatible with chance [exact P = .31], while the exact 95% confidence interval for the odds ratio is wide and includes unity ... The trial also reported more mild-moderate respiratory events with abatacept than with placebo [43.2% vs. 23.5%], including cough, rhonchi, COPD exacerbation, COPD, dyspnea, and nasal congestion. This difference resulted in an odds ration of 1.84,” with a wide confidence interval that included unity (0.48-8.63).

Nevertheless, these findings led to the addition of a warning in the prescribing insert: “Adult COPD patients treated with Orencia developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. Use of Orencia in patients with RA and COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.”

Dr. Suissa’s team used the U.S. MarketScan prescribing database to asses the risk of respiratory adverse events associated with abatacept, compared with other biologic disease-modifying antirheumatic drugs (DMARDs) in a real-world setting.

The cohort comprised 1,807 patients with rheumatoid arthritis and COPD who started a new prescription for abatacept, matched in time to 3,547 who initiated another biologic DMARD. The primary endpoint was the combined risk of hospitalization for COPD exacerbation, bronchitis, and hospitalized pneumonia or influenza.

The most common comparator biologic DMARDs were etanercept, adalimumab, rituximab, and infliximab.

For patients with COPD and comparator patients, the incidence rates for COPD exacerbation were 1.2 per 100 person-years with abatacept and 2.1 per 100 person-years with a different biologic DMARD; for bronchitis, the respective rates were 4.2 and 5.3; for hospitalized pneumonia or influenza, 3.6 and 2.6; and for outpatient pneumonia or flu, 14.7 and 14.4. For the combined endpoint, the incidence rate was 8.7 per 100 person-years with abatacept and 9.9 per 100 person-years with other biologic DMARDs.

The adjusted hazard ratio of the combined endpoint with abatacept versus that with other biologic DMARDs was a nonsignificant risk of 0.87. The hazard ratio with abatacept was 0.60 for hospitalized COPD; 0.80 for bronchitis; 1.39 for hospitalized pneumonia and flu; and 1.05 for outpatient pneumonia and flu. None of these associations was statistically significant.

“One exception was the risk of hospitalization for pneumonia or influenza, which was higher with abatacept among patients with more severe COPD,” at 6.99, than it was with other biologic DMARDs, the authors noted.

Dr. Suissa disclosed relationships with AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Novartis.

msullivan@mdedge.com

SOURCE: Suissa S et al. Semin Arthritis Rheum. 2019 Mar 16. doi: 10.1016j.semarthrit.2019.03.007.
 

Concerns about abatacept (Orencia)-related lung disease in patients with rheumatoid arthritis appear to be unfounded, a large U.S. database review has determined.

designer491/Thinkstock

Safety signals seen in a small subset of patients in the 2006 ASSURE study likely arose from chance, Samy Suissa, PhD, and his colleagues wrote in Seminars in Arthritis & Rheumatism. Patients in that study with preexisting chronic obstructive pulmonary disease (COPD) were 84% more likely to develop an exacerbation or other lung disorder than were those taking a placebo comparator.

The new database study contradicted that finding.

“Our study suggests that these numerical differences in ASSURE are expected results of random variation and thus compatible with chance,” Dr. Suissa of Jewish General Hospital and McGill University, both in Montreal, and his coauthors wrote. “Moreover, our findings are consistent with two studies of the safety of abatacept in the context of interstitial lung disease, albeit a different respiratory disease than COPD.”

The year-long ASSURE trial reported on the safety of abatacept in 959 patients versus 482 assigned to placebo. The safety signal arose in a subgroup of 54 patients with COPD, 37 of whom were assigned to abatacept and 17 to placebo. Among these were four serious respiratory adverse events (COPD exacerbation, worsening of COPD, bronchitis, and pneumonia) in four patients taking abatacept and none in the placebo arm.

“It is useful to note that this difference of 11% versus 0% rate is compatible with chance [exact P = .31], while the exact 95% confidence interval for the odds ratio is wide and includes unity ... The trial also reported more mild-moderate respiratory events with abatacept than with placebo [43.2% vs. 23.5%], including cough, rhonchi, COPD exacerbation, COPD, dyspnea, and nasal congestion. This difference resulted in an odds ration of 1.84,” with a wide confidence interval that included unity (0.48-8.63).

Nevertheless, these findings led to the addition of a warning in the prescribing insert: “Adult COPD patients treated with Orencia developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. Use of Orencia in patients with RA and COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.”

Dr. Suissa’s team used the U.S. MarketScan prescribing database to asses the risk of respiratory adverse events associated with abatacept, compared with other biologic disease-modifying antirheumatic drugs (DMARDs) in a real-world setting.

The cohort comprised 1,807 patients with rheumatoid arthritis and COPD who started a new prescription for abatacept, matched in time to 3,547 who initiated another biologic DMARD. The primary endpoint was the combined risk of hospitalization for COPD exacerbation, bronchitis, and hospitalized pneumonia or influenza.

The most common comparator biologic DMARDs were etanercept, adalimumab, rituximab, and infliximab.

For patients with COPD and comparator patients, the incidence rates for COPD exacerbation were 1.2 per 100 person-years with abatacept and 2.1 per 100 person-years with a different biologic DMARD; for bronchitis, the respective rates were 4.2 and 5.3; for hospitalized pneumonia or influenza, 3.6 and 2.6; and for outpatient pneumonia or flu, 14.7 and 14.4. For the combined endpoint, the incidence rate was 8.7 per 100 person-years with abatacept and 9.9 per 100 person-years with other biologic DMARDs.

The adjusted hazard ratio of the combined endpoint with abatacept versus that with other biologic DMARDs was a nonsignificant risk of 0.87. The hazard ratio with abatacept was 0.60 for hospitalized COPD; 0.80 for bronchitis; 1.39 for hospitalized pneumonia and flu; and 1.05 for outpatient pneumonia and flu. None of these associations was statistically significant.

“One exception was the risk of hospitalization for pneumonia or influenza, which was higher with abatacept among patients with more severe COPD,” at 6.99, than it was with other biologic DMARDs, the authors noted.

Dr. Suissa disclosed relationships with AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Novartis.

msullivan@mdedge.com

SOURCE: Suissa S et al. Semin Arthritis Rheum. 2019 Mar 16. doi: 10.1016j.semarthrit.2019.03.007.