Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

 

 

Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

 

 

Micrograph showing DLBCL

 

The chimeric antigen receptor (CAR) T-cell therapy JCAR017 has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and access to the European Medicines Agency’s (EMA) Priority Medicines (PRIME) program.

JCAR017 has gained access to the PRIME program as a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The breakthrough designation is for JCAR017 in the treatment of patients with relapsed/refractory, aggressive, large B-cell non-Hodgkin lymphoma, including DLBCL not otherwise specified (de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.

JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain. The product is being developed by Juno Therapeutics, Inc. and Celgene Corporation.

The breakthrough therapy designation and PRIME eligibility for JCAR017 were granted by the FDA and EMA, respectively, on the basis of early clinical results with JCAR017 in relapsed/refractory DLBCL.

Results from a phase 1 trial of JCAR017 in relapsed/refractory DLBCL and mantle cell lymphoma were recently presented at the 2016 ASH Annual Meeting (abstract 4192).

About the PRIME program

The goal of the EMA’s PRIME program is to accelerate the development of therapies that target unmet medical needs.

The program provides enhanced EMA support and increased interaction to developers, in order to optimize development plans and speed regulatory evaluations to potentially bring these therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

About breakthrough designation

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

Shridevi Subramaniam

Photo courtesy of ESMO

SINGAPORE—Cancer survivors in Malaysia may have impaired health-related quality of life (HRQOL) and high levels of psychological distress 1 year after diagnosis, according to research presented at the ESMO Asia 2016 Congress.*

Of all the patients studied, those with lymphoma had the lowest global health score (according to the EORTC QLQ C30 questionnaire) and the highest levels of psychological distress (anxiety and depression).

“We urgently need new ways of supporting cancer survivors and addressing wider aspects of wellbeing,” said study investigator Shridevi Subramaniam, of the Clinical Research Centre, Ministry of Health Malaysia, in Kuala Lumpur.

“Instead of just focusing on clinical outcome, doctors must focus equally on quality of life for cancer patients, especially psychologically, financially, and socially.”

Patient population

Subramaniam and her colleagues assessed HRQOL in 1376 cancer patients who had survived 12 months from diagnosis. The patients’ mean age was 52, and 64% were female.

Patients had breast cancer (n=403), lymphomas (n=349), colorectal cancer (n=160), mouth cancer (n=108), and female reproductive cancer (n=91).

Forty-one percent of patients had late-stage cancer, 30% had early stage, and 29% had hematologic cancer. Twenty-eight percent of patients had comorbidities.

Thirty-five percent of patients underwent surgery, 73% received chemotherapy, 43% received radiotherapy, and 13% received hormonal therapy.

Forty-six percent of patients were treated at public hospitals, 48% were treated at academic hospitals, and 6% were treated at private hospitals.

Nearly three-quarters of patients (73%) had no insurance, 20% had private insurance, 5% had insurance via their employers, and 4% had other insurance. Forty-one percent of patients had low income status, 30% middle income, and 20% high income.

Overall HRQOL

The patients reported their HRQOL using the EORTC QLQ C30, Hospital Anxiety and Depression Scale, and EQ-5D questionnaire.

For the entire patient cohort, EORTC QLQ-Q30 scores were as follows:

• Mean global health score—53.0
• Mean physical function score—72.6
• Mean emotional function score—63.0
• Mean fatigue score—32.3
• Mean pain score—26.5

The patients’ mean generic HRQOL index score (according to EQ-5D) was 0.7. And a majority of patients reported anxiety (83.5%, n=949) and depression (79.1%, n=899).

HRQOL by cancer type

Anxiety and depression was most common among patients with lymphoma. These patients also had the lowest global health score. Subramaniam said these findings might be explained by side effects from aggressive treatment.

Mean global health scores were 33.3 for lymphoma patients, 59.4 for female breast cancer patients, 59.6 for colorectal cancer patients, 59.8 for patients with mouth cancer, and 67.8 for patients with female reproductive cancers.

The generic HRQOL index scores were 0.69 (colorectal), 0.73 (lymphoma, breast, and mouth), and 0.80 (reproductive).

The proportion of patients with anxiety was 94% (lymphoma), 87.4% (colorectal), 80.5% (breast), 72.6% (mouth), and 51.7% (reproductive).

The proportion of patients with depression was 86.7% (lymphoma), 80.9% (colorectal), 75.8% (mouth), 74.4% (breast), and 50.5% (reproductive).

Predictors of HRQOL

Subramaniam and her colleagues found several significant predictors of HRQOL.

Older patients had decreased physical function and global health, as well as increased pain and fatigue. Married patients had increased fatigue. And patients without comorbidities had increased physical and emotional function as well as decreased fatigue.

Compared with those treated at private hospitals, patients treated at academic hospitals had decreased physical and emotional functions and increased fatigue. Subramaniam said this could be due to long wait times at academic hospitals, which lead to worsening conditions and more pain and discomfort.

Compared to patients with high income status, those from low income groups had increased global health and physical and emotional functions, as well as decreased pain and fatigue. Subramaniam said this could be due to higher expectations among patients with higher incomes.

Compared to patients with early stage cancers, patients with hematologic and late stage cancers had decreased global health and physical function, as well as increased pain and fatigue. Subramaniam said this could be attributed to side effects of treatment.

She added that treatment side effects might also explain why patients who did not receive chemotherapy had higher global health scores.

Patients who didn’t receive radiotherapy were twice as likely as those who did to report psychological distress. And Subramaniam attributed this to a loss of hope among patients who were not treated.

Patients treated in public and academic hospitals were less likely to be psychologically distressed than those treated in private centers. Subramaniam said this could be related to financial distress.

In closing, Subramaniam said this study indicates that cancer survivors in Malaysia have impaired HRQOL, and many experience psychological distress. Therefore, clinicians should focus on “supporting patients throughout their whole cancer ‘journey,’ especially in their lives after treatment.”

*Abstract 496O_PR—“Health-related quality of life and psychological distress among cancer survivors in a middle-income Asian country.” (Information in the abstract differs from the presentation.)

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com
 

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com
 

NEW ORLEANS – Performing bariatric surgery prior to total knee or hip replacement instead of vice versa resulted in significantly shorter orthopedic surgical operating time and length of stay in an observational study, Emanuel E. Nearing II, MD, reported at Obesity Week 2016.

“We propose that strong consideration be given to bariatric surgery as a means of weight loss and BMI [body mass index] reduction in patients with obesity prior to total joint replacement,” he said at the meeting presented by the Obesity Society of America and the American Society for Metabolic and Bariatric Surgery.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com
 

This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at pdnews@frontlinemedcom.com.

This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at pdnews@frontlinemedcom.com.

This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at pdnews@frontlinemedcom.com.

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

aotto@frontlinemedcom.com

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

aotto@frontlinemedcom.com

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

aotto@frontlinemedcom.com

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock