Photo courtesy of Janssen

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®).

With this sNDA, Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc., are seeking approval for ibrutinib in combination with obinutuzumab (Gazyva®) in previously untreated adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

Ibrutinib is already FDA-approved as monotherapy for adults with CLL/SLL (previously treated or untreated), with and without 17p deletion. Ibrutinib is also approved in combination with bendamustine and rituximab for adults with previously treated CLL/SLL.

Obinutuzumab is FDA-approved for use in combination with chlorambucil to treat previously untreated CLL.

The sNDA for ibrutinib in combination with obinutuzumab is based on results from the phase 3 iLLUMINATE trial (NCT02264574).

The trial is a comparison of ibrutinib plus obinutuzumab and chlorambucil plus obinutuzumab in patients with previously untreated CLL/SLL.

In May, AbbVie announced that the trial’s primary endpoint was met. Specifically, ibrutinib plus obinutuzumab was associated with significantly longer progression-free survival than chlorambucil plus obinutuzumab.

Data from the trial have not been released. Pharmacyclics and Janssen said they plan to present the data in a future publication or at a medical congress.

Photo courtesy of Janssen

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®).

With this sNDA, Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc., are seeking approval for ibrutinib in combination with obinutuzumab (Gazyva®) in previously untreated adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

Ibrutinib is already FDA-approved as monotherapy for adults with CLL/SLL (previously treated or untreated), with and without 17p deletion. Ibrutinib is also approved in combination with bendamustine and rituximab for adults with previously treated CLL/SLL.

Obinutuzumab is FDA-approved for use in combination with chlorambucil to treat previously untreated CLL.

The sNDA for ibrutinib in combination with obinutuzumab is based on results from the phase 3 iLLUMINATE trial (NCT02264574).

The trial is a comparison of ibrutinib plus obinutuzumab and chlorambucil plus obinutuzumab in patients with previously untreated CLL/SLL.

In May, AbbVie announced that the trial’s primary endpoint was met. Specifically, ibrutinib plus obinutuzumab was associated with significantly longer progression-free survival than chlorambucil plus obinutuzumab.

Data from the trial have not been released. Pharmacyclics and Janssen said they plan to present the data in a future publication or at a medical congress.

Photo courtesy of Janssen

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica®).

With this sNDA, Pharmacyclics LLC (an AbbVie company) and Janssen Biotech, Inc., are seeking approval for ibrutinib in combination with obinutuzumab (Gazyva®) in previously untreated adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

Ibrutinib is already FDA-approved as monotherapy for adults with CLL/SLL (previously treated or untreated), with and without 17p deletion. Ibrutinib is also approved in combination with bendamustine and rituximab for adults with previously treated CLL/SLL.

Obinutuzumab is FDA-approved for use in combination with chlorambucil to treat previously untreated CLL.

The sNDA for ibrutinib in combination with obinutuzumab is based on results from the phase 3 iLLUMINATE trial (NCT02264574).

The trial is a comparison of ibrutinib plus obinutuzumab and chlorambucil plus obinutuzumab in patients with previously untreated CLL/SLL.

In May, AbbVie announced that the trial’s primary endpoint was met. Specifically, ibrutinib plus obinutuzumab was associated with significantly longer progression-free survival than chlorambucil plus obinutuzumab.

Data from the trial have not been released. Pharmacyclics and Janssen said they plan to present the data in a future publication or at a medical congress.

The FP was concerned about a possible melanoma due to the dark pigmentation and the positive “ABDCE criteria” of melanoma. The FP used his dermatoscope to determine whether this was a melanoma or a pigmented basal cell carcinoma (BCC).

The multiple leaf-like structures and blue-gray ovoid nests seen with dermoscopy suggested that this was a pigmented BCC. (The ulceration could be seen in either melanoma or BCC.) The FP told the patient that this was most certainly a skin cancer and she needed a biopsy that day. The patient consented and anesthesia was obtained with 1% lidocaine and epinephrine. The physician used a DermaBlade to perform a deep shave (saucerization) under the pigmentation. (See the Watch & Learn video on “Shave biopsy.”)

The pathology confirmed pigmented BCC. The physician recommended an elliptical excision and scheduled it for the following week.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP was concerned about a possible melanoma due to the dark pigmentation and the positive “ABDCE criteria” of melanoma. The FP used his dermatoscope to determine whether this was a melanoma or a pigmented basal cell carcinoma (BCC).

The multiple leaf-like structures and blue-gray ovoid nests seen with dermoscopy suggested that this was a pigmented BCC. (The ulceration could be seen in either melanoma or BCC.) The FP told the patient that this was most certainly a skin cancer and she needed a biopsy that day. The patient consented and anesthesia was obtained with 1% lidocaine and epinephrine. The physician used a DermaBlade to perform a deep shave (saucerization) under the pigmentation. (See the Watch & Learn video on “Shave biopsy.”)

The pathology confirmed pigmented BCC. The physician recommended an elliptical excision and scheduled it for the following week.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP was concerned about a possible melanoma due to the dark pigmentation and the positive “ABDCE criteria” of melanoma. The FP used his dermatoscope to determine whether this was a melanoma or a pigmented basal cell carcinoma (BCC).

The multiple leaf-like structures and blue-gray ovoid nests seen with dermoscopy suggested that this was a pigmented BCC. (The ulceration could be seen in either melanoma or BCC.) The FP told the patient that this was most certainly a skin cancer and she needed a biopsy that day. The patient consented and anesthesia was obtained with 1% lidocaine and epinephrine. The physician used a DermaBlade to perform a deep shave (saucerization) under the pigmentation. (See the Watch & Learn video on “Shave biopsy.”)

The pathology confirmed pigmented BCC. The physician recommended an elliptical excision and scheduled it for the following week.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.

The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.

“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.

The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.

Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.

New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).

Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.

The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.

According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.

The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.

Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.

Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.

“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.

“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.

They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.

None of the authors declared any financial or other conflicts of interest.

SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.

Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.

The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.

“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.

The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.

Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.

New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).

Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.

The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.

According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.

The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.

Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.

Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.

“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.

“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.

They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.

None of the authors declared any financial or other conflicts of interest.

SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.

Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.

The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.

“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.

The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.

Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.

New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).

Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.

The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.

According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.

The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.

Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.

Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.

“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.

“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.

They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.

None of the authors declared any financial or other conflicts of interest.

SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.

BERLIN—MD1003, a high-dose pharmaceutical grade biotin, is effective in the treatment of patients with progressive multiple sclerosis (MS), according to a report presented at ECTRIMS 2018. “This real-world study supports the growing body of evidence that MD1003 is an effective and safe treatment for progressive MS,” said lead author Jonathan Ciron, MD, of the Department of Neurology, CHU Toulouse, France, and colleagues.

In the 2016 MS-SPI study, MD1003 treatment was shown to be effective and well tolerated in patients with progressive MS. Notably, MD1003 reversed MS-related disease disability in 13% of patients with progressive MS. Based on these findings, MD1003 is currently being prescribed to patients with progressive MS in France under an expanded access program.

In the present study, Dr. Ciron and colleagues sought to determine the benefits, in terms of effectiveness and safety, of MD1003 in patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) in a clinical center.

MD1003 300 mg/day (100 mg tid) was prescribed to patients with PPMS or SPMS receiving care at a single center in France (CHU Toulouse) starting in January 2016. The following measures of effectiveness and safety were administered: Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25W), nine-hole peg test (9-HPT), number of relapses, and gadolinium-enhancing lesions on T1-weighted images.

As of May 2018, a total of 220 patients received MD1003. The research team presented the results of the first 91 patients to complete one year of follow-up. At baseline, mean age was 59.5, 61.5% were female, 70.3% had SPMS, mean EDSS was 5.9, mean T25W was 50.7 seconds, 9-HPT in the dominant hand was 35.1 seconds, and the mean number of previous relapses was 5.1. After one year of treatment with MD1003, 19 (23%; n = 83 with data) patients experienced improvement in EDSS and 15 (23%; n = 66 with data) patients experienced 20% or greater improvement in T25W. Active disease, a clinically-defined relapse, or a gadolinium-enhancing T1 lesion was observed in nine (11%; n = 79 with data) patients. MD1003 was also well tolerated, the researchers noted.

BERLIN—MD1003, a high-dose pharmaceutical grade biotin, is effective in the treatment of patients with progressive multiple sclerosis (MS), according to a report presented at ECTRIMS 2018. “This real-world study supports the growing body of evidence that MD1003 is an effective and safe treatment for progressive MS,” said lead author Jonathan Ciron, MD, of the Department of Neurology, CHU Toulouse, France, and colleagues.

In the 2016 MS-SPI study, MD1003 treatment was shown to be effective and well tolerated in patients with progressive MS. Notably, MD1003 reversed MS-related disease disability in 13% of patients with progressive MS. Based on these findings, MD1003 is currently being prescribed to patients with progressive MS in France under an expanded access program.

In the present study, Dr. Ciron and colleagues sought to determine the benefits, in terms of effectiveness and safety, of MD1003 in patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) in a clinical center.

MD1003 300 mg/day (100 mg tid) was prescribed to patients with PPMS or SPMS receiving care at a single center in France (CHU Toulouse) starting in January 2016. The following measures of effectiveness and safety were administered: Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25W), nine-hole peg test (9-HPT), number of relapses, and gadolinium-enhancing lesions on T1-weighted images.

As of May 2018, a total of 220 patients received MD1003. The research team presented the results of the first 91 patients to complete one year of follow-up. At baseline, mean age was 59.5, 61.5% were female, 70.3% had SPMS, mean EDSS was 5.9, mean T25W was 50.7 seconds, 9-HPT in the dominant hand was 35.1 seconds, and the mean number of previous relapses was 5.1. After one year of treatment with MD1003, 19 (23%; n = 83 with data) patients experienced improvement in EDSS and 15 (23%; n = 66 with data) patients experienced 20% or greater improvement in T25W. Active disease, a clinically-defined relapse, or a gadolinium-enhancing T1 lesion was observed in nine (11%; n = 79 with data) patients. MD1003 was also well tolerated, the researchers noted.

BERLIN—MD1003, a high-dose pharmaceutical grade biotin, is effective in the treatment of patients with progressive multiple sclerosis (MS), according to a report presented at ECTRIMS 2018. “This real-world study supports the growing body of evidence that MD1003 is an effective and safe treatment for progressive MS,” said lead author Jonathan Ciron, MD, of the Department of Neurology, CHU Toulouse, France, and colleagues.

In the 2016 MS-SPI study, MD1003 treatment was shown to be effective and well tolerated in patients with progressive MS. Notably, MD1003 reversed MS-related disease disability in 13% of patients with progressive MS. Based on these findings, MD1003 is currently being prescribed to patients with progressive MS in France under an expanded access program.

In the present study, Dr. Ciron and colleagues sought to determine the benefits, in terms of effectiveness and safety, of MD1003 in patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) in a clinical center.

MD1003 300 mg/day (100 mg tid) was prescribed to patients with PPMS or SPMS receiving care at a single center in France (CHU Toulouse) starting in January 2016. The following measures of effectiveness and safety were administered: Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25W), nine-hole peg test (9-HPT), number of relapses, and gadolinium-enhancing lesions on T1-weighted images.

As of May 2018, a total of 220 patients received MD1003. The research team presented the results of the first 91 patients to complete one year of follow-up. At baseline, mean age was 59.5, 61.5% were female, 70.3% had SPMS, mean EDSS was 5.9, mean T25W was 50.7 seconds, 9-HPT in the dominant hand was 35.1 seconds, and the mean number of previous relapses was 5.1. After one year of treatment with MD1003, 19 (23%; n = 83 with data) patients experienced improvement in EDSS and 15 (23%; n = 66 with data) patients experienced 20% or greater improvement in T25W. Active disease, a clinically-defined relapse, or a gadolinium-enhancing T1 lesion was observed in nine (11%; n = 79 with data) patients. MD1003 was also well tolerated, the researchers noted.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

utah778/Thinkstock

A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

utah778/Thinkstock

A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.

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A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.

Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.

In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.

While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.

In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.

Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.

In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.

“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.

The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.

“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”

The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.

“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”

The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.

SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.

Life (and mice) find a way

anyaivanova/iStock/Getty Images Plus

Apparently we have learned nothing from “Jurassic Park.” This time, though, we might get a world overrun by ... mice? Researchers in China have utilized the complex science of gene editing to help same-sex mice couples bear offspring. This is the first time both female-female and male-male pairs have produced pups (previously, only the female pairs were able to carry to full term) using CRISPR-Cas9. The experiment also served as a study in the relative uselessness of males: All the pups born of male pairs died shortly after birth. Researchers are hopeful to move on to bigger mammals including monkeys, which could eventually turn this “Jurassic Park” adventure into a full-on “Planet of the Apes” nightmare. Best of luck to them!

Hold me closer, tiny robot

Gentleman, we’ve all been put on notice. A team from the University of Exeter in England has taken the next step toward redundancy for the male of the species: robot sperm. Now that we’ve got your attention, take a deep breath and relax. It’s not that bad. The idea is for the robot sperm, or “torque-driven ferromagnetic swimmers,” to be used to deliver drugs, not DNA, the investigators explained. Each millimeter-long device consists “of a magnetic head and flexible tail that allows them to ‘swim’ to a specific location when activated by a magnetic field,” they said. “Developing this technology could radically change the way we do medicine. The swimmers could one day be used to direct drugs to the right areas of the body by swimming through blood vessels,” senior investigator Feodor Ogrin said. So, it looks like it’s going to be okay for men after all. Still, we have to wonder, how long will it be before Siri and Alexa try to make a withdrawal from the robot sperm bank?

Eavesdropping on the brain

Talaj/iStock/Getty Images Plus

Does this count as mind reading? A team of scientists and clinicians from the University of Cambridge has created a new method of testing brain function after tumor removal. The current method of running through cognitive tests while a patient is awake and the brain is exposed is painless (albeit objectively horrifying) but can be risky, and the current cognitive tests can be limited. This new approach is much safer – everyone wears protective gloves and gently massages the brain while singing “Kumbaya” ... Just kidding. Clinicians actually use MRI to examine the brain before surgery and determine how different regions of that ball of gray matter communicate with each other. A 3D-printed model of the patient’s brain is also provided, both as a handy 3D map and a fun souvenir! Because that’s what the world of medicine is missing: a gift shop.

Cannabinoids. Period.

Jedraszak/iStock/Getty Images Plus

When other medical news columns go high, we go low. How anatomically low? “Cannabis-infused vaginal suppositories.” Those of you about to be made reproductively moot by robot sperm and CRISPR-Cas9 should stop with the junior-high smirking. Because our more mature readers may be interested in an upcoming study. Foria Wellness is ready to put its cannabinoid-infused menstrual pain relief product, Foria Relief, to the test this fall in an observational study of 400 women. The suppositories deliver 60 mg of tetrahydrocannabinol and 10 mg of cannabidiol to their target. The company claims it’s a natural, side-effect–free analgesic alternative to hormonal birth control, ibuprofen, and opioids. And unlike unsuppositoried cannabinoid pain products that waft from place to place around a user’s system, Foria Relief promises sustained focus on its specific task. A quality that smirking junior-high types often lack.

Life (and mice) find a way

anyaivanova/iStock/Getty Images Plus

Apparently we have learned nothing from “Jurassic Park.” This time, though, we might get a world overrun by ... mice? Researchers in China have utilized the complex science of gene editing to help same-sex mice couples bear offspring. This is the first time both female-female and male-male pairs have produced pups (previously, only the female pairs were able to carry to full term) using CRISPR-Cas9. The experiment also served as a study in the relative uselessness of males: All the pups born of male pairs died shortly after birth. Researchers are hopeful to move on to bigger mammals including monkeys, which could eventually turn this “Jurassic Park” adventure into a full-on “Planet of the Apes” nightmare. Best of luck to them!

Hold me closer, tiny robot

Gentleman, we’ve all been put on notice. A team from the University of Exeter in England has taken the next step toward redundancy for the male of the species: robot sperm. Now that we’ve got your attention, take a deep breath and relax. It’s not that bad. The idea is for the robot sperm, or “torque-driven ferromagnetic swimmers,” to be used to deliver drugs, not DNA, the investigators explained. Each millimeter-long device consists “of a magnetic head and flexible tail that allows them to ‘swim’ to a specific location when activated by a magnetic field,” they said. “Developing this technology could radically change the way we do medicine. The swimmers could one day be used to direct drugs to the right areas of the body by swimming through blood vessels,” senior investigator Feodor Ogrin said. So, it looks like it’s going to be okay for men after all. Still, we have to wonder, how long will it be before Siri and Alexa try to make a withdrawal from the robot sperm bank?

Eavesdropping on the brain

Talaj/iStock/Getty Images Plus

Does this count as mind reading? A team of scientists and clinicians from the University of Cambridge has created a new method of testing brain function after tumor removal. The current method of running through cognitive tests while a patient is awake and the brain is exposed is painless (albeit objectively horrifying) but can be risky, and the current cognitive tests can be limited. This new approach is much safer – everyone wears protective gloves and gently massages the brain while singing “Kumbaya” ... Just kidding. Clinicians actually use MRI to examine the brain before surgery and determine how different regions of that ball of gray matter communicate with each other. A 3D-printed model of the patient’s brain is also provided, both as a handy 3D map and a fun souvenir! Because that’s what the world of medicine is missing: a gift shop.

Cannabinoids. Period.

Jedraszak/iStock/Getty Images Plus

When other medical news columns go high, we go low. How anatomically low? “Cannabis-infused vaginal suppositories.” Those of you about to be made reproductively moot by robot sperm and CRISPR-Cas9 should stop with the junior-high smirking. Because our more mature readers may be interested in an upcoming study. Foria Wellness is ready to put its cannabinoid-infused menstrual pain relief product, Foria Relief, to the test this fall in an observational study of 400 women. The suppositories deliver 60 mg of tetrahydrocannabinol and 10 mg of cannabidiol to their target. The company claims it’s a natural, side-effect–free analgesic alternative to hormonal birth control, ibuprofen, and opioids. And unlike unsuppositoried cannabinoid pain products that waft from place to place around a user’s system, Foria Relief promises sustained focus on its specific task. A quality that smirking junior-high types often lack.

Life (and mice) find a way

anyaivanova/iStock/Getty Images Plus

Apparently we have learned nothing from “Jurassic Park.” This time, though, we might get a world overrun by ... mice? Researchers in China have utilized the complex science of gene editing to help same-sex mice couples bear offspring. This is the first time both female-female and male-male pairs have produced pups (previously, only the female pairs were able to carry to full term) using CRISPR-Cas9. The experiment also served as a study in the relative uselessness of males: All the pups born of male pairs died shortly after birth. Researchers are hopeful to move on to bigger mammals including monkeys, which could eventually turn this “Jurassic Park” adventure into a full-on “Planet of the Apes” nightmare. Best of luck to them!

Hold me closer, tiny robot

Gentleman, we’ve all been put on notice. A team from the University of Exeter in England has taken the next step toward redundancy for the male of the species: robot sperm. Now that we’ve got your attention, take a deep breath and relax. It’s not that bad. The idea is for the robot sperm, or “torque-driven ferromagnetic swimmers,” to be used to deliver drugs, not DNA, the investigators explained. Each millimeter-long device consists “of a magnetic head and flexible tail that allows them to ‘swim’ to a specific location when activated by a magnetic field,” they said. “Developing this technology could radically change the way we do medicine. The swimmers could one day be used to direct drugs to the right areas of the body by swimming through blood vessels,” senior investigator Feodor Ogrin said. So, it looks like it’s going to be okay for men after all. Still, we have to wonder, how long will it be before Siri and Alexa try to make a withdrawal from the robot sperm bank?

Eavesdropping on the brain

Talaj/iStock/Getty Images Plus

Does this count as mind reading? A team of scientists and clinicians from the University of Cambridge has created a new method of testing brain function after tumor removal. The current method of running through cognitive tests while a patient is awake and the brain is exposed is painless (albeit objectively horrifying) but can be risky, and the current cognitive tests can be limited. This new approach is much safer – everyone wears protective gloves and gently massages the brain while singing “Kumbaya” ... Just kidding. Clinicians actually use MRI to examine the brain before surgery and determine how different regions of that ball of gray matter communicate with each other. A 3D-printed model of the patient’s brain is also provided, both as a handy 3D map and a fun souvenir! Because that’s what the world of medicine is missing: a gift shop.

Cannabinoids. Period.

Jedraszak/iStock/Getty Images Plus

When other medical news columns go high, we go low. How anatomically low? “Cannabis-infused vaginal suppositories.” Those of you about to be made reproductively moot by robot sperm and CRISPR-Cas9 should stop with the junior-high smirking. Because our more mature readers may be interested in an upcoming study. Foria Wellness is ready to put its cannabinoid-infused menstrual pain relief product, Foria Relief, to the test this fall in an observational study of 400 women. The suppositories deliver 60 mg of tetrahydrocannabinol and 10 mg of cannabidiol to their target. The company claims it’s a natural, side-effect–free analgesic alternative to hormonal birth control, ibuprofen, and opioids. And unlike unsuppositoried cannabinoid pain products that waft from place to place around a user’s system, Foria Relief promises sustained focus on its specific task. A quality that smirking junior-high types often lack.

BARCELONA – Individuals who regularly consume alcohol in quantities defined by the World Health Organization as “very high risk” face a daunting and yet widely underappreciated health burden, Rainer Spanagel, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

He cited a recent study led by Jürgen Rehm, PhD, of the Centre for Addiction and Mental Health in Toronto in which the investigators estimated the prevalence of what the WHO has defined as a “very-high-risk drinking level” among people aged 15-65 years in 13 E.U. countries. The researchers then went on to determine the associated annual risk of disease and injury, as well as the effects on life expectancy.

“The numbers are so shocking that you have to take it seriously,” said Dr. Spanagel, chair of the department of psychopharmacology at the Central Institute of Mental Health in Mannheim, Germany.

Nearly 2 decades ago, the WHO defined very-high-risk level of alcohol consumption as more than 100 g/day of ethanol for men and more than 60 g/day for women. That translates to a threshold of 7.1 and 4.3 standard drinks – a 12-ounce beer, 5-ounce glass of wine, or 1.5-ounce serving of liquor – on a daily basis.

“This WHO categorization of drinking risk levels has been pretty much ignored in clinical trials and epidemiologic studies until 3 or 4 years ago,” according to Dr. Spanagel.

The study by Dr. Rehm and his colleagues suggests this has been a serious mistake. By using data from the WHO’s Global Information System on Alcohol and Health, as well as from clinical trials, the investigators determined that the prevalence of this level of alcohol consumption was less than 1% overall across 13 European countries. However, rates varied markedly: in excess of 4% in Ireland and more than 3.5% in the United Kingdom, compared with less than 0.5% in Germany, Sweden, Denmark, Finland, Hungary, and the Netherlands. The Czech Republic came in at about 3%, while Italy, Spain, France, and Austria had rates of more than 0.5% but less than 1%.

The investigators estimated that the risk of disease or injury associated with this very-high-risk drinking level was 13.5% per year. Based on data from nine E.U. countries, Dr. Rehm and his colleagues found that a very-high-risk level of alcohol consumption caused nearly 54% of all cases of hepatic cirrhosis in those countries, 41% of esophageal and oral cancers, and 44% of pancreatitis.

Life expectancy in the European Union stands at 80.6 years. The investigators calculated on the basis of comprehensive French national mortality data that very-high-risk level alcohol intake resulted in a 22-year reduction in life expectancy, compared with the general population. By comparison, all cancers considered together resulted in 10 years of life lost.

Dr. Spanagel is editor in chief of the journal Addiction Biology, in which this study appeared (Addict Biol. 2018 Jul;23[4]:961-8).

[email protected]

BARCELONA – Individuals who regularly consume alcohol in quantities defined by the World Health Organization as “very high risk” face a daunting and yet widely underappreciated health burden, Rainer Spanagel, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

He cited a recent study led by Jürgen Rehm, PhD, of the Centre for Addiction and Mental Health in Toronto in which the investigators estimated the prevalence of what the WHO has defined as a “very-high-risk drinking level” among people aged 15-65 years in 13 E.U. countries. The researchers then went on to determine the associated annual risk of disease and injury, as well as the effects on life expectancy.

“The numbers are so shocking that you have to take it seriously,” said Dr. Spanagel, chair of the department of psychopharmacology at the Central Institute of Mental Health in Mannheim, Germany.

Nearly 2 decades ago, the WHO defined very-high-risk level of alcohol consumption as more than 100 g/day of ethanol for men and more than 60 g/day for women. That translates to a threshold of 7.1 and 4.3 standard drinks – a 12-ounce beer, 5-ounce glass of wine, or 1.5-ounce serving of liquor – on a daily basis.

“This WHO categorization of drinking risk levels has been pretty much ignored in clinical trials and epidemiologic studies until 3 or 4 years ago,” according to Dr. Spanagel.

The study by Dr. Rehm and his colleagues suggests this has been a serious mistake. By using data from the WHO’s Global Information System on Alcohol and Health, as well as from clinical trials, the investigators determined that the prevalence of this level of alcohol consumption was less than 1% overall across 13 European countries. However, rates varied markedly: in excess of 4% in Ireland and more than 3.5% in the United Kingdom, compared with less than 0.5% in Germany, Sweden, Denmark, Finland, Hungary, and the Netherlands. The Czech Republic came in at about 3%, while Italy, Spain, France, and Austria had rates of more than 0.5% but less than 1%.

The investigators estimated that the risk of disease or injury associated with this very-high-risk drinking level was 13.5% per year. Based on data from nine E.U. countries, Dr. Rehm and his colleagues found that a very-high-risk level of alcohol consumption caused nearly 54% of all cases of hepatic cirrhosis in those countries, 41% of esophageal and oral cancers, and 44% of pancreatitis.

Life expectancy in the European Union stands at 80.6 years. The investigators calculated on the basis of comprehensive French national mortality data that very-high-risk level alcohol intake resulted in a 22-year reduction in life expectancy, compared with the general population. By comparison, all cancers considered together resulted in 10 years of life lost.

Dr. Spanagel is editor in chief of the journal Addiction Biology, in which this study appeared (Addict Biol. 2018 Jul;23[4]:961-8).

[email protected]

BARCELONA – Individuals who regularly consume alcohol in quantities defined by the World Health Organization as “very high risk” face a daunting and yet widely underappreciated health burden, Rainer Spanagel, MD, observed at the annual congress of the European College of Neuropsychopharmacology.

He cited a recent study led by Jürgen Rehm, PhD, of the Centre for Addiction and Mental Health in Toronto in which the investigators estimated the prevalence of what the WHO has defined as a “very-high-risk drinking level” among people aged 15-65 years in 13 E.U. countries. The researchers then went on to determine the associated annual risk of disease and injury, as well as the effects on life expectancy.

“The numbers are so shocking that you have to take it seriously,” said Dr. Spanagel, chair of the department of psychopharmacology at the Central Institute of Mental Health in Mannheim, Germany.

Nearly 2 decades ago, the WHO defined very-high-risk level of alcohol consumption as more than 100 g/day of ethanol for men and more than 60 g/day for women. That translates to a threshold of 7.1 and 4.3 standard drinks – a 12-ounce beer, 5-ounce glass of wine, or 1.5-ounce serving of liquor – on a daily basis.

“This WHO categorization of drinking risk levels has been pretty much ignored in clinical trials and epidemiologic studies until 3 or 4 years ago,” according to Dr. Spanagel.

The study by Dr. Rehm and his colleagues suggests this has been a serious mistake. By using data from the WHO’s Global Information System on Alcohol and Health, as well as from clinical trials, the investigators determined that the prevalence of this level of alcohol consumption was less than 1% overall across 13 European countries. However, rates varied markedly: in excess of 4% in Ireland and more than 3.5% in the United Kingdom, compared with less than 0.5% in Germany, Sweden, Denmark, Finland, Hungary, and the Netherlands. The Czech Republic came in at about 3%, while Italy, Spain, France, and Austria had rates of more than 0.5% but less than 1%.

The investigators estimated that the risk of disease or injury associated with this very-high-risk drinking level was 13.5% per year. Based on data from nine E.U. countries, Dr. Rehm and his colleagues found that a very-high-risk level of alcohol consumption caused nearly 54% of all cases of hepatic cirrhosis in those countries, 41% of esophageal and oral cancers, and 44% of pancreatitis.

Life expectancy in the European Union stands at 80.6 years. The investigators calculated on the basis of comprehensive French national mortality data that very-high-risk level alcohol intake resulted in a 22-year reduction in life expectancy, compared with the general population. By comparison, all cancers considered together resulted in 10 years of life lost.

Dr. Spanagel is editor in chief of the journal Addiction Biology, in which this study appeared (Addict Biol. 2018 Jul;23[4]:961-8).

[email protected]

BARCELONA – Among the handful of top publications on mood disorders during the first three-quarters of 2018 was a landmark comparison of the efficacy and acceptability of 21 antidepressants for acute treatment of major depressive disorder, Íria Grande, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Dr. Grande, a psychiatrist at the bipolar disorders clinic of the University of Barcelona, shared her personal top picks.
 

‘Antidepressants work’

This epic systematic review and network meta-analysis (Lancet. 2018 Apr 7;391[10128]:1357-66) encompassed 522 randomized double-blind trials with 116,477 participants with major depressive disorder assigned to 21 antidepressants or placebo, in some instances with an additional active comparator antidepressant arm. The report is a major extension of previous work by the same multinational group of investigators (Lancet. 2009 Feb 28;373[9665]:746-58), who initially scrutinized 12 older antidepressants in a total population only one-quarter the size of the updated analysis.

Based upon this vast randomized trial evidence, some of which came from unpublished studies tracked down by the investigators, the 21 antidepressants were rank-ordered in terms of effectiveness and acceptability. But in Dr. Grande’s view, the most important study finding wasn’t which antidepressant donned the crown of most effective or patient acceptable, it was the fact that all 21 drugs proved significantly more effective than placebo, with odds ratios ranging from 2.13 at the top end to 1.37 for reboxetine.

“The results showed antidepressants work. All of the antipsychiatry system is trying to show us that antidepressants do not work in major depression. Well, in this study, it has been proven that all antidepressants are more effective than placebo in major depressive disorder. I think social media should be made aware of that. (Lead investigator) Dr. Andrea Cipriani talked on the BBC about this article, and it had a high impact,” according to Dr. Grande.

All but three of the 21 antidepressants were deemed to be as acceptable as placebo, based upon study dropout rates. The exceptions were agomelatine and fluoxetine, which were 12%-14% more acceptable than placebo. “That’s strange, I think, but that’s what the clinical trial results showed,” she noted. The findings on clomipramine, which was 30% less acceptable than placebo, make sense, Dr. Grande said, “due to its muscarinic effects.”

She took issue with some of the specific study findings. For example, the two top-rated antidepressants in terms of efficacy were amitriptyline and mirtazapine, with odds ratios of 2.13 and 1.89, respectively.

“As a clinician, I don’t consider mirtazapine to be one of the best antidepressants, especially in major depression,” she said. “But these are the results, and as always, we have to adapt the evidence-based medicine and consider it from our clinical point of view.”

The investigators conducted a subanalysis restricted to placebo-controlled head-to-head studies with a comparator antidepressant which Dr. Grande found more interesting and informative than the overall analysis. In the head-to-head analysis, vortioxetine emerged as the top-rated antidepressant, both in efficacy, with an odds ratio of 2.0, as well as in acceptability.
 

Lithium vs. quetiapine

Finnish investigators used prospective national databases to examine the rates of psychiatric and all-cause hospitalization during a mean 7.2 years of follow-up in all 18,018 Finns hospitalized for bipolar disorder. The purpose was to assess the impact of various mood stabilizers on overall health outcomes in a real-world setting.

The big winner was lithium. In an analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, and intervals of drug exposure and nonexposure, lithium was associated with the lowest risks of psychiatric rehospitalization and all-cause hospitalization, with relative risk reductions of 33% and 29%, respectively. In contrast, quetiapine, the most widely used antipsychotic agent, paled by comparison, achieving only an 8% reduction in the risk of psychiatric rehospitalization and a 7% decrease in all-cause hospitalization (JAMA Psychiatry. 2018 Apr 1;75[4]:347-55).

In addition, long-acting injectable antipsychotics were significantly more effective for prevention of hospitalization than oral antipsychotics.

“That is kind of shocking, because in some countries, long-acting injectables are not authorized and cannot be used. But I think after this article some regulatory changes are going to take place as a result,” Dr. Grande predicted.

“Another issue I thought was interesting, although it was not the main aim of the study, involved benzodiazepines. They increased the risk of hospitalizations, both for psychiatric illness and all other causes. So apart from giving lithium and long-acting injectable antipsychotics to our bipolar patients, we should also be really careful about the use of benzodiazepines,” she commented.
 

Intranasal esketamine for suicidality?

Esketamine nasal spray, a fast-acting N-methyl-D-aspartate antagonist whose application for marketing approval in combination with a standard oral antidepressant in treatment-resistant depression is now under Food and Drug Administration review, also is being developed for another indication: reduction of suicidality in patients at imminent suicide risk. In a proof-of-concept study, intranasal esketamine resulted in a significant reduction in suicidal thoughts 4 hours after administration, compared with usual care – but not at 24 hours (Am J Psychiatry. 2018 Jul 1;175[7]:620-30).

Phase 3 trials of intranasal esketamine for reduction of suicidality are ongoing. New and effective medications for this indication are sorely needed. The only drug approved for the indication of suicide prevention is clozapine.
 

‘Latest thinking’ on bipolar disorders

Dr. Grande coauthored a comprehensive review article on bipolar disorders that she recommended as worthwhile reading (Nat Rev Dis Primers. 2018 Mar 8;4:18008. doi: 10.1038/nrdp.2018.8).

“It covers all the latest thinking. It focuses on the early stages of the disorder, how epigenetic factors are essential, and many other topics, including the bipolarity index being developed at the University of Barcelona to classify drugs in terms of their capacity to prevent episodes of mania or depression in terms of number needed to treat and number needed to harm. It emphasizes the importance of intervening early and focusing on cognitive dysfunction,” Dr Grande said.
 

Psychedelics making a comeback

German and Swiss investigators used a facial expression discrimination task to demonstrate that psilocybin, a 5-hydroxytryptamine_2A–receptor agonist, decreases connectivity between the amygdala and regions of the brain important in emotion processing, including the striatum and frontal pole. The investigators theorized that this might be the mechanism for the psychedelic’s apparent antidepressant effects (Eur Neuropsychopharmacol. 2018 Jun;28[6]:691-700).

Dr. Grande included this study in her top publications list because it reflects the rapidly growing rebirth of interest in psychedelics research among European psychiatrists.

Indeed, elsewhere at the ECNP congress David J. Nutt, DM, declared, “We now have the beginnings of some swinging of the pendulum back in a modern direction. Over the last 10 years there have been a small number of open studies, all done with psilocybin, which is somewhat easier to use than LSD. There are studies in OCD [obsessive-compulsive disorder], tobacco dependence, alcoholism, resistant depression, end-of-life mood changes with cancer and other terminal diseases, and at least two ongoing randomized trials in resistant depression.”

Dr. Nutt, professor of neuropsychopharmacology at Imperial College London, was senior author of the first proof-of-concept study of psilocybin accompanied by psychologic support as a novel therapy for moderate to severe treatment-resistant major depression (Lancet Psychiatry. 2016 Jul;3[7]:619-27).
 

Methylphenidate ineffective for treatment of acute mania

The MEMAP study was a randomized, double-blind, placebo-controlled multicenter clinical trial testing what has been called the vigilance regulation model of mania. This model hypothesized that unstable regulation of wakefulness figures prominently in the pathogenesis of both mania and attention-deficit/hyperactivity disorder. If true, investigators reasoned, then 2.5 days of methylphenidate at 20-40 mg/day should have a rapid antimanic effect similar to the drug’s benefits in ADHD. Dr. Grande had been a skeptic, and indeed, the trial was halted early for futility (Eur Neuropsychopharmacol. 2018 Jan;28[1]:185-94).

She reported serving as a paid speaker for Lunbeck, Ferrer, GlaxoSmithKline, and Janssen. Her own research is funded by the Spanish Ministry of Economy and Competitiveness.

[email protected]

BARCELONA – Among the handful of top publications on mood disorders during the first three-quarters of 2018 was a landmark comparison of the efficacy and acceptability of 21 antidepressants for acute treatment of major depressive disorder, Íria Grande, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Dr. Grande, a psychiatrist at the bipolar disorders clinic of the University of Barcelona, shared her personal top picks.
 

‘Antidepressants work’

This epic systematic review and network meta-analysis (Lancet. 2018 Apr 7;391[10128]:1357-66) encompassed 522 randomized double-blind trials with 116,477 participants with major depressive disorder assigned to 21 antidepressants or placebo, in some instances with an additional active comparator antidepressant arm. The report is a major extension of previous work by the same multinational group of investigators (Lancet. 2009 Feb 28;373[9665]:746-58), who initially scrutinized 12 older antidepressants in a total population only one-quarter the size of the updated analysis.

Based upon this vast randomized trial evidence, some of which came from unpublished studies tracked down by the investigators, the 21 antidepressants were rank-ordered in terms of effectiveness and acceptability. But in Dr. Grande’s view, the most important study finding wasn’t which antidepressant donned the crown of most effective or patient acceptable, it was the fact that all 21 drugs proved significantly more effective than placebo, with odds ratios ranging from 2.13 at the top end to 1.37 for reboxetine.

“The results showed antidepressants work. All of the antipsychiatry system is trying to show us that antidepressants do not work in major depression. Well, in this study, it has been proven that all antidepressants are more effective than placebo in major depressive disorder. I think social media should be made aware of that. (Lead investigator) Dr. Andrea Cipriani talked on the BBC about this article, and it had a high impact,” according to Dr. Grande.

All but three of the 21 antidepressants were deemed to be as acceptable as placebo, based upon study dropout rates. The exceptions were agomelatine and fluoxetine, which were 12%-14% more acceptable than placebo. “That’s strange, I think, but that’s what the clinical trial results showed,” she noted. The findings on clomipramine, which was 30% less acceptable than placebo, make sense, Dr. Grande said, “due to its muscarinic effects.”

She took issue with some of the specific study findings. For example, the two top-rated antidepressants in terms of efficacy were amitriptyline and mirtazapine, with odds ratios of 2.13 and 1.89, respectively.

“As a clinician, I don’t consider mirtazapine to be one of the best antidepressants, especially in major depression,” she said. “But these are the results, and as always, we have to adapt the evidence-based medicine and consider it from our clinical point of view.”

The investigators conducted a subanalysis restricted to placebo-controlled head-to-head studies with a comparator antidepressant which Dr. Grande found more interesting and informative than the overall analysis. In the head-to-head analysis, vortioxetine emerged as the top-rated antidepressant, both in efficacy, with an odds ratio of 2.0, as well as in acceptability.
 

Lithium vs. quetiapine

Finnish investigators used prospective national databases to examine the rates of psychiatric and all-cause hospitalization during a mean 7.2 years of follow-up in all 18,018 Finns hospitalized for bipolar disorder. The purpose was to assess the impact of various mood stabilizers on overall health outcomes in a real-world setting.

The big winner was lithium. In an analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, and intervals of drug exposure and nonexposure, lithium was associated with the lowest risks of psychiatric rehospitalization and all-cause hospitalization, with relative risk reductions of 33% and 29%, respectively. In contrast, quetiapine, the most widely used antipsychotic agent, paled by comparison, achieving only an 8% reduction in the risk of psychiatric rehospitalization and a 7% decrease in all-cause hospitalization (JAMA Psychiatry. 2018 Apr 1;75[4]:347-55).

In addition, long-acting injectable antipsychotics were significantly more effective for prevention of hospitalization than oral antipsychotics.

“That is kind of shocking, because in some countries, long-acting injectables are not authorized and cannot be used. But I think after this article some regulatory changes are going to take place as a result,” Dr. Grande predicted.

“Another issue I thought was interesting, although it was not the main aim of the study, involved benzodiazepines. They increased the risk of hospitalizations, both for psychiatric illness and all other causes. So apart from giving lithium and long-acting injectable antipsychotics to our bipolar patients, we should also be really careful about the use of benzodiazepines,” she commented.
 

Intranasal esketamine for suicidality?

Esketamine nasal spray, a fast-acting N-methyl-D-aspartate antagonist whose application for marketing approval in combination with a standard oral antidepressant in treatment-resistant depression is now under Food and Drug Administration review, also is being developed for another indication: reduction of suicidality in patients at imminent suicide risk. In a proof-of-concept study, intranasal esketamine resulted in a significant reduction in suicidal thoughts 4 hours after administration, compared with usual care – but not at 24 hours (Am J Psychiatry. 2018 Jul 1;175[7]:620-30).

Phase 3 trials of intranasal esketamine for reduction of suicidality are ongoing. New and effective medications for this indication are sorely needed. The only drug approved for the indication of suicide prevention is clozapine.
 

‘Latest thinking’ on bipolar disorders

Dr. Grande coauthored a comprehensive review article on bipolar disorders that she recommended as worthwhile reading (Nat Rev Dis Primers. 2018 Mar 8;4:18008. doi: 10.1038/nrdp.2018.8).

“It covers all the latest thinking. It focuses on the early stages of the disorder, how epigenetic factors are essential, and many other topics, including the bipolarity index being developed at the University of Barcelona to classify drugs in terms of their capacity to prevent episodes of mania or depression in terms of number needed to treat and number needed to harm. It emphasizes the importance of intervening early and focusing on cognitive dysfunction,” Dr Grande said.
 

Psychedelics making a comeback

German and Swiss investigators used a facial expression discrimination task to demonstrate that psilocybin, a 5-hydroxytryptamine_2A–receptor agonist, decreases connectivity between the amygdala and regions of the brain important in emotion processing, including the striatum and frontal pole. The investigators theorized that this might be the mechanism for the psychedelic’s apparent antidepressant effects (Eur Neuropsychopharmacol. 2018 Jun;28[6]:691-700).

Dr. Grande included this study in her top publications list because it reflects the rapidly growing rebirth of interest in psychedelics research among European psychiatrists.

Indeed, elsewhere at the ECNP congress David J. Nutt, DM, declared, “We now have the beginnings of some swinging of the pendulum back in a modern direction. Over the last 10 years there have been a small number of open studies, all done with psilocybin, which is somewhat easier to use than LSD. There are studies in OCD [obsessive-compulsive disorder], tobacco dependence, alcoholism, resistant depression, end-of-life mood changes with cancer and other terminal diseases, and at least two ongoing randomized trials in resistant depression.”

Dr. Nutt, professor of neuropsychopharmacology at Imperial College London, was senior author of the first proof-of-concept study of psilocybin accompanied by psychologic support as a novel therapy for moderate to severe treatment-resistant major depression (Lancet Psychiatry. 2016 Jul;3[7]:619-27).
 

Methylphenidate ineffective for treatment of acute mania

The MEMAP study was a randomized, double-blind, placebo-controlled multicenter clinical trial testing what has been called the vigilance regulation model of mania. This model hypothesized that unstable regulation of wakefulness figures prominently in the pathogenesis of both mania and attention-deficit/hyperactivity disorder. If true, investigators reasoned, then 2.5 days of methylphenidate at 20-40 mg/day should have a rapid antimanic effect similar to the drug’s benefits in ADHD. Dr. Grande had been a skeptic, and indeed, the trial was halted early for futility (Eur Neuropsychopharmacol. 2018 Jan;28[1]:185-94).

She reported serving as a paid speaker for Lunbeck, Ferrer, GlaxoSmithKline, and Janssen. Her own research is funded by the Spanish Ministry of Economy and Competitiveness.

[email protected]

BARCELONA – Among the handful of top publications on mood disorders during the first three-quarters of 2018 was a landmark comparison of the efficacy and acceptability of 21 antidepressants for acute treatment of major depressive disorder, Íria Grande, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Dr. Grande, a psychiatrist at the bipolar disorders clinic of the University of Barcelona, shared her personal top picks.
 

‘Antidepressants work’

This epic systematic review and network meta-analysis (Lancet. 2018 Apr 7;391[10128]:1357-66) encompassed 522 randomized double-blind trials with 116,477 participants with major depressive disorder assigned to 21 antidepressants or placebo, in some instances with an additional active comparator antidepressant arm. The report is a major extension of previous work by the same multinational group of investigators (Lancet. 2009 Feb 28;373[9665]:746-58), who initially scrutinized 12 older antidepressants in a total population only one-quarter the size of the updated analysis.

Based upon this vast randomized trial evidence, some of which came from unpublished studies tracked down by the investigators, the 21 antidepressants were rank-ordered in terms of effectiveness and acceptability. But in Dr. Grande’s view, the most important study finding wasn’t which antidepressant donned the crown of most effective or patient acceptable, it was the fact that all 21 drugs proved significantly more effective than placebo, with odds ratios ranging from 2.13 at the top end to 1.37 for reboxetine.

“The results showed antidepressants work. All of the antipsychiatry system is trying to show us that antidepressants do not work in major depression. Well, in this study, it has been proven that all antidepressants are more effective than placebo in major depressive disorder. I think social media should be made aware of that. (Lead investigator) Dr. Andrea Cipriani talked on the BBC about this article, and it had a high impact,” according to Dr. Grande.

All but three of the 21 antidepressants were deemed to be as acceptable as placebo, based upon study dropout rates. The exceptions were agomelatine and fluoxetine, which were 12%-14% more acceptable than placebo. “That’s strange, I think, but that’s what the clinical trial results showed,” she noted. The findings on clomipramine, which was 30% less acceptable than placebo, make sense, Dr. Grande said, “due to its muscarinic effects.”

She took issue with some of the specific study findings. For example, the two top-rated antidepressants in terms of efficacy were amitriptyline and mirtazapine, with odds ratios of 2.13 and 1.89, respectively.

“As a clinician, I don’t consider mirtazapine to be one of the best antidepressants, especially in major depression,” she said. “But these are the results, and as always, we have to adapt the evidence-based medicine and consider it from our clinical point of view.”

The investigators conducted a subanalysis restricted to placebo-controlled head-to-head studies with a comparator antidepressant which Dr. Grande found more interesting and informative than the overall analysis. In the head-to-head analysis, vortioxetine emerged as the top-rated antidepressant, both in efficacy, with an odds ratio of 2.0, as well as in acceptability.
 

Lithium vs. quetiapine

Finnish investigators used prospective national databases to examine the rates of psychiatric and all-cause hospitalization during a mean 7.2 years of follow-up in all 18,018 Finns hospitalized for bipolar disorder. The purpose was to assess the impact of various mood stabilizers on overall health outcomes in a real-world setting.

The big winner was lithium. In an analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, and intervals of drug exposure and nonexposure, lithium was associated with the lowest risks of psychiatric rehospitalization and all-cause hospitalization, with relative risk reductions of 33% and 29%, respectively. In contrast, quetiapine, the most widely used antipsychotic agent, paled by comparison, achieving only an 8% reduction in the risk of psychiatric rehospitalization and a 7% decrease in all-cause hospitalization (JAMA Psychiatry. 2018 Apr 1;75[4]:347-55).

In addition, long-acting injectable antipsychotics were significantly more effective for prevention of hospitalization than oral antipsychotics.

“That is kind of shocking, because in some countries, long-acting injectables are not authorized and cannot be used. But I think after this article some regulatory changes are going to take place as a result,” Dr. Grande predicted.

“Another issue I thought was interesting, although it was not the main aim of the study, involved benzodiazepines. They increased the risk of hospitalizations, both for psychiatric illness and all other causes. So apart from giving lithium and long-acting injectable antipsychotics to our bipolar patients, we should also be really careful about the use of benzodiazepines,” she commented.
 

Intranasal esketamine for suicidality?

Esketamine nasal spray, a fast-acting N-methyl-D-aspartate antagonist whose application for marketing approval in combination with a standard oral antidepressant in treatment-resistant depression is now under Food and Drug Administration review, also is being developed for another indication: reduction of suicidality in patients at imminent suicide risk. In a proof-of-concept study, intranasal esketamine resulted in a significant reduction in suicidal thoughts 4 hours after administration, compared with usual care – but not at 24 hours (Am J Psychiatry. 2018 Jul 1;175[7]:620-30).

Phase 3 trials of intranasal esketamine for reduction of suicidality are ongoing. New and effective medications for this indication are sorely needed. The only drug approved for the indication of suicide prevention is clozapine.
 

‘Latest thinking’ on bipolar disorders

Dr. Grande coauthored a comprehensive review article on bipolar disorders that she recommended as worthwhile reading (Nat Rev Dis Primers. 2018 Mar 8;4:18008. doi: 10.1038/nrdp.2018.8).

“It covers all the latest thinking. It focuses on the early stages of the disorder, how epigenetic factors are essential, and many other topics, including the bipolarity index being developed at the University of Barcelona to classify drugs in terms of their capacity to prevent episodes of mania or depression in terms of number needed to treat and number needed to harm. It emphasizes the importance of intervening early and focusing on cognitive dysfunction,” Dr Grande said.
 

Psychedelics making a comeback

German and Swiss investigators used a facial expression discrimination task to demonstrate that psilocybin, a 5-hydroxytryptamine_2A–receptor agonist, decreases connectivity between the amygdala and regions of the brain important in emotion processing, including the striatum and frontal pole. The investigators theorized that this might be the mechanism for the psychedelic’s apparent antidepressant effects (Eur Neuropsychopharmacol. 2018 Jun;28[6]:691-700).

Dr. Grande included this study in her top publications list because it reflects the rapidly growing rebirth of interest in psychedelics research among European psychiatrists.

Indeed, elsewhere at the ECNP congress David J. Nutt, DM, declared, “We now have the beginnings of some swinging of the pendulum back in a modern direction. Over the last 10 years there have been a small number of open studies, all done with psilocybin, which is somewhat easier to use than LSD. There are studies in OCD [obsessive-compulsive disorder], tobacco dependence, alcoholism, resistant depression, end-of-life mood changes with cancer and other terminal diseases, and at least two ongoing randomized trials in resistant depression.”

Dr. Nutt, professor of neuropsychopharmacology at Imperial College London, was senior author of the first proof-of-concept study of psilocybin accompanied by psychologic support as a novel therapy for moderate to severe treatment-resistant major depression (Lancet Psychiatry. 2016 Jul;3[7]:619-27).
 

Methylphenidate ineffective for treatment of acute mania

The MEMAP study was a randomized, double-blind, placebo-controlled multicenter clinical trial testing what has been called the vigilance regulation model of mania. This model hypothesized that unstable regulation of wakefulness figures prominently in the pathogenesis of both mania and attention-deficit/hyperactivity disorder. If true, investigators reasoned, then 2.5 days of methylphenidate at 20-40 mg/day should have a rapid antimanic effect similar to the drug’s benefits in ADHD. Dr. Grande had been a skeptic, and indeed, the trial was halted early for futility (Eur Neuropsychopharmacol. 2018 Jan;28[1]:185-94).

She reported serving as a paid speaker for Lunbeck, Ferrer, GlaxoSmithKline, and Janssen. Her own research is funded by the Spanish Ministry of Economy and Competitiveness.

[email protected]

PHILADELPHIA – A novel score accurately predicted the size and presence of esophageal varices in a noninvasive manner, which may help clinicians avoid unnecessary esophagogastroduodenoscopy in patients with cirrhosis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although there are two validated scores for predicting esophageal varices (EV), platelet count to spleen diameter ratio and Baveno VI criteria, they have drawbacks, Tien Dong, MD, from the University of California, Los Angeles said.

“The limitations to these existing scores and criteria are both of them require imaging to do, so because of that, they oftentimes are limited in national clinical use,” Dr. Dong said in his presentation of his team’s abstract, which won the ACG Governors Award for Excellence in Clinical Research. “The other thing is that, even though it’s recommended, sometimes spleen diameter on a normal ultrasound is not reported. Furthermore, elastography – even though it’s becoming more and more common – is still not yet readily available across the country.”

Dr. Dong and his colleagues sought to identify noninvasive clinical predictors of EV to create a predictive score to identify EV to overcome these drawbacks. They gathered endoscopy data from the Olive View–UCLA and West Los Angeles Veterans Affairs Hospital to create a discovery cohort (165 patients) and tested the score on patients from Ronald Reagan UCLA Medical Center in a validation cohort (73 patients).

They used a random forest classifier machine learning algorithm “to create a forest of decision trees so that it can tell us which variables it believes to be the most predictive of our outcomes of interest,” Dr. Dong said.

The algorithm identified several variables that appeared to be predictive of EV presence, such as international normalized ratio, aminotransferase, platelet mean, hemoglobin, albumin and blood urea nitrogen less than or equal to 3, which the researchers used to create an EV-endoscopy (EV-Endo) score.

In the discovery cohort, area under the curve (AUC) for the presence of EV was 0.81, compared with an AUC of 0.82 in the validation cohort, while there was an AUC of 0.77 in the discovery cohort and an AUC of 0.79 for small/absent vs. medium/large EV. Patients with Child-Pugh class A cirrhosis had an AUC of 0.81 for EV presence and an AUC of 0.77 for EV size. The researchers then created a cutoff score of 3.48 or less and 7.70 or more for EV presence, which had a sensitivity and specificity of 93.9% and 97.5%, respectively. EV-Endo score EV size cutoff scores were also 3.48 or less and 7.70 or more, with a sensitivity of 95.8% and specificity of 95.0%.

Dr. Dong reports no conflicts of interest.

SOURCE: Hauer M et al. ACG 2018. Presentation 31.

PHILADELPHIA – A novel score accurately predicted the size and presence of esophageal varices in a noninvasive manner, which may help clinicians avoid unnecessary esophagogastroduodenoscopy in patients with cirrhosis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although there are two validated scores for predicting esophageal varices (EV), platelet count to spleen diameter ratio and Baveno VI criteria, they have drawbacks, Tien Dong, MD, from the University of California, Los Angeles said.

“The limitations to these existing scores and criteria are both of them require imaging to do, so because of that, they oftentimes are limited in national clinical use,” Dr. Dong said in his presentation of his team’s abstract, which won the ACG Governors Award for Excellence in Clinical Research. “The other thing is that, even though it’s recommended, sometimes spleen diameter on a normal ultrasound is not reported. Furthermore, elastography – even though it’s becoming more and more common – is still not yet readily available across the country.”

Dr. Dong and his colleagues sought to identify noninvasive clinical predictors of EV to create a predictive score to identify EV to overcome these drawbacks. They gathered endoscopy data from the Olive View–UCLA and West Los Angeles Veterans Affairs Hospital to create a discovery cohort (165 patients) and tested the score on patients from Ronald Reagan UCLA Medical Center in a validation cohort (73 patients).

They used a random forest classifier machine learning algorithm “to create a forest of decision trees so that it can tell us which variables it believes to be the most predictive of our outcomes of interest,” Dr. Dong said.

The algorithm identified several variables that appeared to be predictive of EV presence, such as international normalized ratio, aminotransferase, platelet mean, hemoglobin, albumin and blood urea nitrogen less than or equal to 3, which the researchers used to create an EV-endoscopy (EV-Endo) score.

In the discovery cohort, area under the curve (AUC) for the presence of EV was 0.81, compared with an AUC of 0.82 in the validation cohort, while there was an AUC of 0.77 in the discovery cohort and an AUC of 0.79 for small/absent vs. medium/large EV. Patients with Child-Pugh class A cirrhosis had an AUC of 0.81 for EV presence and an AUC of 0.77 for EV size. The researchers then created a cutoff score of 3.48 or less and 7.70 or more for EV presence, which had a sensitivity and specificity of 93.9% and 97.5%, respectively. EV-Endo score EV size cutoff scores were also 3.48 or less and 7.70 or more, with a sensitivity of 95.8% and specificity of 95.0%.

Dr. Dong reports no conflicts of interest.

SOURCE: Hauer M et al. ACG 2018. Presentation 31.

PHILADELPHIA – A novel score accurately predicted the size and presence of esophageal varices in a noninvasive manner, which may help clinicians avoid unnecessary esophagogastroduodenoscopy in patients with cirrhosis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

Although there are two validated scores for predicting esophageal varices (EV), platelet count to spleen diameter ratio and Baveno VI criteria, they have drawbacks, Tien Dong, MD, from the University of California, Los Angeles said.

“The limitations to these existing scores and criteria are both of them require imaging to do, so because of that, they oftentimes are limited in national clinical use,” Dr. Dong said in his presentation of his team’s abstract, which won the ACG Governors Award for Excellence in Clinical Research. “The other thing is that, even though it’s recommended, sometimes spleen diameter on a normal ultrasound is not reported. Furthermore, elastography – even though it’s becoming more and more common – is still not yet readily available across the country.”

Dr. Dong and his colleagues sought to identify noninvasive clinical predictors of EV to create a predictive score to identify EV to overcome these drawbacks. They gathered endoscopy data from the Olive View–UCLA and West Los Angeles Veterans Affairs Hospital to create a discovery cohort (165 patients) and tested the score on patients from Ronald Reagan UCLA Medical Center in a validation cohort (73 patients).

They used a random forest classifier machine learning algorithm “to create a forest of decision trees so that it can tell us which variables it believes to be the most predictive of our outcomes of interest,” Dr. Dong said.

The algorithm identified several variables that appeared to be predictive of EV presence, such as international normalized ratio, aminotransferase, platelet mean, hemoglobin, albumin and blood urea nitrogen less than or equal to 3, which the researchers used to create an EV-endoscopy (EV-Endo) score.

In the discovery cohort, area under the curve (AUC) for the presence of EV was 0.81, compared with an AUC of 0.82 in the validation cohort, while there was an AUC of 0.77 in the discovery cohort and an AUC of 0.79 for small/absent vs. medium/large EV. Patients with Child-Pugh class A cirrhosis had an AUC of 0.81 for EV presence and an AUC of 0.77 for EV size. The researchers then created a cutoff score of 3.48 or less and 7.70 or more for EV presence, which had a sensitivity and specificity of 93.9% and 97.5%, respectively. EV-Endo score EV size cutoff scores were also 3.48 or less and 7.70 or more, with a sensitivity of 95.8% and specificity of 95.0%.

Dr. Dong reports no conflicts of interest.

SOURCE: Hauer M et al. ACG 2018. Presentation 31.

Gastroenterology

How and when to consider genetic testing for colon cancer? Ballester V; Cruz-Correa M. 2018 Oct;155(4):955-9. doi: 10.1053/j.gastro.2018.08.031.

How to approach a patient with eosinophilic esophagitis. Hirano I. 2018 Sept;155(3):601-6. doi: 10.1053/j.gastro.2018.08.001.

How to ensure patient adherence to colorectal cancer screening and surveillance in your practice. Hassan C; Kaminski MF; Repici A. 2018 Aug;155(2):252-7. doi: 10.1053/j.gastro.2018.06.051.

How to approach difficult patient encounters: ROAR. McCarthy JG; Cheatham JG; Singla M. 2018 Aug;155(2):258-61. doi: 10.1053/j.gastro.2018.06.052.

An inside view: AGA advocacy priorities. Jain R. 2018 Aug;155(2):572-3. doi: 10.1053/j.gastro.2018.06.028.

Clin Gastro Hepatol

Adding value to the conversation about colorectal cancer screening: Practical pearls for gastroenterologists. Maratt JK; Naylor K; Saini SD. 2018 Oct;16(10):1545–8. doi: 10.1016/j.cgh.2018.07.002.

Credentialing for endoscopic practice: The Mayo Clinic model. Kane SV; Chandrasekhara V; Sedlack RE; Buttar NS. 2018 Sept;16(9):1370–3.e1 doi: 10.1016/j.cgh.2018.06.020.

Gastroenterology

How and when to consider genetic testing for colon cancer? Ballester V; Cruz-Correa M. 2018 Oct;155(4):955-9. doi: 10.1053/j.gastro.2018.08.031.

How to approach a patient with eosinophilic esophagitis. Hirano I. 2018 Sept;155(3):601-6. doi: 10.1053/j.gastro.2018.08.001.

How to ensure patient adherence to colorectal cancer screening and surveillance in your practice. Hassan C; Kaminski MF; Repici A. 2018 Aug;155(2):252-7. doi: 10.1053/j.gastro.2018.06.051.

How to approach difficult patient encounters: ROAR. McCarthy JG; Cheatham JG; Singla M. 2018 Aug;155(2):258-61. doi: 10.1053/j.gastro.2018.06.052.

An inside view: AGA advocacy priorities. Jain R. 2018 Aug;155(2):572-3. doi: 10.1053/j.gastro.2018.06.028.

Clin Gastro Hepatol

Adding value to the conversation about colorectal cancer screening: Practical pearls for gastroenterologists. Maratt JK; Naylor K; Saini SD. 2018 Oct;16(10):1545–8. doi: 10.1016/j.cgh.2018.07.002.

Credentialing for endoscopic practice: The Mayo Clinic model. Kane SV; Chandrasekhara V; Sedlack RE; Buttar NS. 2018 Sept;16(9):1370–3.e1 doi: 10.1016/j.cgh.2018.06.020.

Gastroenterology

How and when to consider genetic testing for colon cancer? Ballester V; Cruz-Correa M. 2018 Oct;155(4):955-9. doi: 10.1053/j.gastro.2018.08.031.

How to approach a patient with eosinophilic esophagitis. Hirano I. 2018 Sept;155(3):601-6. doi: 10.1053/j.gastro.2018.08.001.

How to ensure patient adherence to colorectal cancer screening and surveillance in your practice. Hassan C; Kaminski MF; Repici A. 2018 Aug;155(2):252-7. doi: 10.1053/j.gastro.2018.06.051.

How to approach difficult patient encounters: ROAR. McCarthy JG; Cheatham JG; Singla M. 2018 Aug;155(2):258-61. doi: 10.1053/j.gastro.2018.06.052.

An inside view: AGA advocacy priorities. Jain R. 2018 Aug;155(2):572-3. doi: 10.1053/j.gastro.2018.06.028.

Clin Gastro Hepatol

Adding value to the conversation about colorectal cancer screening: Practical pearls for gastroenterologists. Maratt JK; Naylor K; Saini SD. 2018 Oct;16(10):1545–8. doi: 10.1016/j.cgh.2018.07.002.

Credentialing for endoscopic practice: The Mayo Clinic model. Kane SV; Chandrasekhara V; Sedlack RE; Buttar NS. 2018 Sept;16(9):1370–3.e1 doi: 10.1016/j.cgh.2018.06.020.