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The Benefits and Risks of Oral Antiplatelet Therapy in Patients With Acute Coronary Syndrome
The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today.
The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today.
The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today.
Ibalizumab suppressed HIV-1 in multidrug-resistant patients
Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.
The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.
Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).
“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log10 reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log10 reduction, compared with 0% during the monitoring period (P less than .0001).
The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.
The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log10, compared with baseline – 55% of patients had a decrease of at least 1 log10, and 48% had a reduction of at least 2 log10; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.
Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.
“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.
She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”
The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.
The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.
Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).
“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log10 reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log10 reduction, compared with 0% during the monitoring period (P less than .0001).
The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.
The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log10, compared with baseline – 55% of patients had a decrease of at least 1 log10, and 48% had a reduction of at least 2 log10; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.
Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.
“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.
She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”
The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
Seattle – The antibody ibalizumab combined with an optimized background regimen maintained viral suppression out to 24 weeks, in an open-label extension study of patients with multidrug-resistant HIV-1 infections.
The researchers had previously shown that the drug achieved viral suppression after 7 days in many patients.
Ibalizumab works by blocking an epitope on the second extracellular domain of the CD4 receptor, preventing the HIV virus from entering the cell. The 40 patients in the study had failed on at least one drug in three different classes, though they had to have sensitivity to at least one antiretroviral drug, which was used to construct the optimized background regimen (OBR).
“These patients are the most vulnerable and most at risk in terms of needing a new class of drugs. This is the first new class of drug that will go for approval in a decade,” said Brinda Emu, MD, of the deparment of internal medicine at Yale University, New Haven, Conn., who presented the study in a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The average duration of HIV infection among patients was 21 years. Forty-three percent had to take the investigational agent fostemsavir as part of their OBR. After a 7-day monitoring period, patients received a 2,000-mg IV dose of ibalizumab. Seven days later, at day 14, 83% had achieved at least a 0.5 log10 reduction in viral load, compared with 3% during the monitoring period (P less than .0001); 60% achieved at least a 1 log10 reduction, compared with 0% during the monitoring period (P less than .0001).
The OBR was then started at week 14, and patients received an injection of 800 mg ibalizumab every 2 weeks beginning at day 21 and continuing until week 24.
The current research reports the results of the extension study. At week 24, the mean viral load had decreased 1.6 log10, compared with baseline – 55% of patients had a decrease of at least 1 log10, and 48% had a reduction of at least 2 log10; 43% of patients had undetectable levels of virus, and 50% had fewer than 200 copies/mL.
Nine patients reported a total of 17 serious adverse events, 1 of which led to drug discontinuation. Overall. there were nine discontinuations due to four deaths, three consent withdrawals, and two losses to follow-up.
“In an indication with very resistant virus and limited options, combining ibalizumab with at least one other active agent can provide a way to decrease viral load and increase CD4+ T cells. What I want to know is, What if we started this a little bit earlier as we do with many of our other drugs?” asked Dr. Emu.
She said that some providers had had concerns that adherence may be low with an injectable drug, but the results were reassuring. “I will say anecdotally that I’ve seen the complete opposite. One of the things we noticed is that seeing these patients every 2 weeks to give them their IV infusions has made them more adherent to the rest of their regimen. Perhaps it’s that ability to check in, and the relationship that builds up over time with your providers. Despite it being an infusional agent, or perhaps because of that, adherence has been pretty good.”
The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
Key clinical point: An extension study showed viral load suppression out to 24 weeks in multidrug-resistant HIV patients.
Major finding: 55% of patients with resistant HIV had viral reduction at week 24.
Data source: A single-arm, open-label study of 40 patients.
Disclosures: The study was funded by TaiMed Biologics. Dr. Emu has served on TaiMed’s advisory board.
Small study: Drug combo achieves negative bacterial culture in all TB patients
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
AT CROI
Key clinical point: An oral, three-drug combination led to undetectable bacteria levels.
Major finding: All of the patients in the study were culture negative at 4 months.
Data source: Open-label trial of 72 patients at two centers.
Disclosures: Dr. Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
Two-drug combo looks good for HIV maintenance therapy
SEATTLE – In HIV patients with suppressed virus and no history of virologic failure, a two-drug combination of dolutegravir and rilpivirine (DTG+RPV) proved noninferior to three- and four-drug regimens in maintaining viral RNA counts at less than 50 copies/mL.
The results come from an integrated analysis of two open-label, multicenter phase III clinical trials – SWORD 1 and SWORD 2 – the results of which were presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The combined studies included 1,024 HIV-1 infected adults who had successful viral suppression on a three- or four-drug current antiretroviral (CAR) therapy. They were randomized to continue CAR or switch to the two-drug regimen.
At week 48, a pooled analysis showed that the percentage of patients with HIV-1 RNA less than 50 copies/mL was 95% in CAR patients and 96% in DTG+RPV patients (difference, –0.6%; 95% confidence interval, –4.3% to 3.0%) in SWORD 1. In SWORD 2, 94% of patients achieved those levels in both arms (difference, –0.2%; 95% CI, –3.9% to 4.2%).
Adverse events were reported in 77% of patients in the DTG+RPV group and 71% of patients in the CAR group, with the most common being nasopharyngitis, headache, upper respiratory tract infection, diarrhea, and back pain. Five percent of patients in the DTG+RPV group had serious adverse events, compared with 4% in the CAR group.
The rate of adverse events leading to study withdrawal was higher in the DTG+RPV group (4%) than the CAR group (less than 1%).
The switch to DTG+RPV had no significant effect on lipid levels, but was associated with improvements in bone biomarkers, including bone-specific alkaline phosphatase (baseline 15.9 mcg/L to 12.9 mcg/L in DTG+RPV versus 16.2 to 17.1 in CAR; P less than .001), osteocalcin (23.8 mcg/L to 19.0 mcg/L in DTG+RPV versus 24.0 to 23.1 in CAR; P less than .001), and procollagen 1 N-terminal propeptide (53.0 mcg/L to 45.6 mcg/L in DTG+RPV versus 55.3 to 54.7 in CAR; P less than .001).
ViiV and Janssen, who sponsored the two studies, have formed a partnership to formulate the two drugs as a single pill, according to Kimberly Smith, MD, MPH, vice president and head of global research and medical strategy at ViiV. “We’re hoping to have the tablet available to people by this time next year,” she said.
The two drugs were chosen for their potency and safety. “Dolutegravir has shown itself to be the most potent integrase inhibitor, it’s well tolerated, and it has a high barrier to resistance. That’s why we thought it would be a good lead drug for a two-drug regimen. We added rilpivirine to it because it’s also a well-tolerated drug. The two have small doses, so we thought we could make a very small pill,” said Dr. Smith.
Joseph Eron, MD, director of Clinical Core at the University of North Carolina, Chapel Hill, who chaired a press conference that discussed the results, noted that the regimen has the potential to have fewer drug interactions. “There are potential distinct advantages to this particular combination.”
SEATTLE – In HIV patients with suppressed virus and no history of virologic failure, a two-drug combination of dolutegravir and rilpivirine (DTG+RPV) proved noninferior to three- and four-drug regimens in maintaining viral RNA counts at less than 50 copies/mL.
The results come from an integrated analysis of two open-label, multicenter phase III clinical trials – SWORD 1 and SWORD 2 – the results of which were presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The combined studies included 1,024 HIV-1 infected adults who had successful viral suppression on a three- or four-drug current antiretroviral (CAR) therapy. They were randomized to continue CAR or switch to the two-drug regimen.
At week 48, a pooled analysis showed that the percentage of patients with HIV-1 RNA less than 50 copies/mL was 95% in CAR patients and 96% in DTG+RPV patients (difference, –0.6%; 95% confidence interval, –4.3% to 3.0%) in SWORD 1. In SWORD 2, 94% of patients achieved those levels in both arms (difference, –0.2%; 95% CI, –3.9% to 4.2%).
Adverse events were reported in 77% of patients in the DTG+RPV group and 71% of patients in the CAR group, with the most common being nasopharyngitis, headache, upper respiratory tract infection, diarrhea, and back pain. Five percent of patients in the DTG+RPV group had serious adverse events, compared with 4% in the CAR group.
The rate of adverse events leading to study withdrawal was higher in the DTG+RPV group (4%) than the CAR group (less than 1%).
The switch to DTG+RPV had no significant effect on lipid levels, but was associated with improvements in bone biomarkers, including bone-specific alkaline phosphatase (baseline 15.9 mcg/L to 12.9 mcg/L in DTG+RPV versus 16.2 to 17.1 in CAR; P less than .001), osteocalcin (23.8 mcg/L to 19.0 mcg/L in DTG+RPV versus 24.0 to 23.1 in CAR; P less than .001), and procollagen 1 N-terminal propeptide (53.0 mcg/L to 45.6 mcg/L in DTG+RPV versus 55.3 to 54.7 in CAR; P less than .001).
ViiV and Janssen, who sponsored the two studies, have formed a partnership to formulate the two drugs as a single pill, according to Kimberly Smith, MD, MPH, vice president and head of global research and medical strategy at ViiV. “We’re hoping to have the tablet available to people by this time next year,” she said.
The two drugs were chosen for their potency and safety. “Dolutegravir has shown itself to be the most potent integrase inhibitor, it’s well tolerated, and it has a high barrier to resistance. That’s why we thought it would be a good lead drug for a two-drug regimen. We added rilpivirine to it because it’s also a well-tolerated drug. The two have small doses, so we thought we could make a very small pill,” said Dr. Smith.
Joseph Eron, MD, director of Clinical Core at the University of North Carolina, Chapel Hill, who chaired a press conference that discussed the results, noted that the regimen has the potential to have fewer drug interactions. “There are potential distinct advantages to this particular combination.”
SEATTLE – In HIV patients with suppressed virus and no history of virologic failure, a two-drug combination of dolutegravir and rilpivirine (DTG+RPV) proved noninferior to three- and four-drug regimens in maintaining viral RNA counts at less than 50 copies/mL.
The results come from an integrated analysis of two open-label, multicenter phase III clinical trials – SWORD 1 and SWORD 2 – the results of which were presented at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
The combined studies included 1,024 HIV-1 infected adults who had successful viral suppression on a three- or four-drug current antiretroviral (CAR) therapy. They were randomized to continue CAR or switch to the two-drug regimen.
At week 48, a pooled analysis showed that the percentage of patients with HIV-1 RNA less than 50 copies/mL was 95% in CAR patients and 96% in DTG+RPV patients (difference, –0.6%; 95% confidence interval, –4.3% to 3.0%) in SWORD 1. In SWORD 2, 94% of patients achieved those levels in both arms (difference, –0.2%; 95% CI, –3.9% to 4.2%).
Adverse events were reported in 77% of patients in the DTG+RPV group and 71% of patients in the CAR group, with the most common being nasopharyngitis, headache, upper respiratory tract infection, diarrhea, and back pain. Five percent of patients in the DTG+RPV group had serious adverse events, compared with 4% in the CAR group.
The rate of adverse events leading to study withdrawal was higher in the DTG+RPV group (4%) than the CAR group (less than 1%).
The switch to DTG+RPV had no significant effect on lipid levels, but was associated with improvements in bone biomarkers, including bone-specific alkaline phosphatase (baseline 15.9 mcg/L to 12.9 mcg/L in DTG+RPV versus 16.2 to 17.1 in CAR; P less than .001), osteocalcin (23.8 mcg/L to 19.0 mcg/L in DTG+RPV versus 24.0 to 23.1 in CAR; P less than .001), and procollagen 1 N-terminal propeptide (53.0 mcg/L to 45.6 mcg/L in DTG+RPV versus 55.3 to 54.7 in CAR; P less than .001).
ViiV and Janssen, who sponsored the two studies, have formed a partnership to formulate the two drugs as a single pill, according to Kimberly Smith, MD, MPH, vice president and head of global research and medical strategy at ViiV. “We’re hoping to have the tablet available to people by this time next year,” she said.
The two drugs were chosen for their potency and safety. “Dolutegravir has shown itself to be the most potent integrase inhibitor, it’s well tolerated, and it has a high barrier to resistance. That’s why we thought it would be a good lead drug for a two-drug regimen. We added rilpivirine to it because it’s also a well-tolerated drug. The two have small doses, so we thought we could make a very small pill,” said Dr. Smith.
Joseph Eron, MD, director of Clinical Core at the University of North Carolina, Chapel Hill, who chaired a press conference that discussed the results, noted that the regimen has the potential to have fewer drug interactions. “There are potential distinct advantages to this particular combination.”
Key clinical point: A two-drug combination could reduce cumulative drug exposure in HIV maintenance.
Major finding: Both two-drug and CAR regimens achieved viral suppression in about 95% of patients at week 48.
Data source: An integrated analysis of two open-label, multicenter phase III clinical trials, SWORD 1 and SWORD 2.
Disclosures: The study was sponsored by ViiV Healthcare and Janssen. Dr. Smith is an employee of Viiv. Dr. Llibre has consulted for ViiV and Janssen. Dr. Eron has received consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Merck, Tibotec/Janssen, and Tobira.
Most lung recipients gain 2-year survival benefit
Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.
In a study published in the February issue of the Annals of the American Thoracic Society, researchers used data from 13,040 adults listed for lung transplantation between May 2005 and September 2011 to develop a structural nested accelerated failure time model of the survival benefit of lung transplantation over time.
“A ‘structural nested model’ is [used to] compare the distribution of counterfactual residual survival if a patient were to receive a transplanted organ with the survival distribution if the patient did not receive that organ and never received one subsequently,” wrote David M. Vock, PhD, from the University of Minnesota, and coauthors.
Using this approach, they calculated that 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with transplantation. At 1 year posttransplantation, the relative survival benefit was 1.59, at 2 years it was 1.93, and at 3 years it was 2.23 (Ann Am Thorac Soc. 2017;14:172-81. doi: 10.1513/AnnalsATS.201606-507OC).
Patients’ lung allocation score at transplantation (LAS-T) – the score used to prioritize donated lungs for transplantation – had a significant impact on the survival benefit from transplantation. The relative survival benefit of transplantation increased by 59.4% as the lung allocation score increased from 30 to 35, and increased by 45.1% as the lung allocation score increased from 50 to 55.
However patients with a lung allocation score of 32.5 or less were more likely to die with a transplant than without, even over the long term, while patients with a score of 35 or more always gained a survival advantage from transplantation, even if their scores were as high as 50-100. The authors said this showed there should be no upper limit for the lung allocation score.
“It has been suggested that the LAS system may encourage patients who have clinically deteriorated to undergo transplantation even though it would be futile,” they wrote. “Our results reinforce the notion that lung transplantation should be considered an appropriate treatment option for patients with most advanced lung diseases and is expected to confer survival benefit in appropriately selected patients.”
Researchers also observed an interesting, borderline significant association between disease group and survival benefit, with individuals with obstructive lung disease showing the lowest relative survival gains and those with cystic fibrosis showing the highest. Head to head, the relative survival benefit of transplantation for those with cystic fibrosis was 54.4% greater than for those with obstructive lung disease.
Other factors such as transplant type, age, smoking, and center volume also influenced relative survival benefit. Bilateral transplants were associated with a 13.4% greater relative survival benefit, lungs from donors aged under 55 years showed a 17.9% relative survival benefit, and lungs from donors without a history of smoking showed a 10.5% increase in relative survival benefit.
However the researchers noted that their modeling focused on only the survival benefit of transplantation and did not take into account improvements in quality of life. This was likely to be particularly relevant in conditions such as chronic obstructive pulmonary disease where the quality of life benefits might justify transplantation even in the absence of a clear survival benefit.
“A comprehensive understanding of the survival benefit of lung transplantation and how that benefit varies by recipient characteristics is imperative to inform recipient selection, to justify the intensive health care resources allocated to this treatment, and to achieve an equitable allocation of donor lungs,” the researchers said.
The study was supported by the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute of Allergy and Infectious Diseases. One author declared grants and personal fees from private industry for consultation on lung transplantation. No other conflicts of interest were declared.
Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.
It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.
Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.
It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.
Lung transplantation is the only option available for patients with treatment-resistant end-stage lung disease. However, the ability of this intervention to extend survival is still actively debated. The authors demonstrate that most adults undergoing lung transplantation experience a survival benefit that is mainly driven by the value of the lung allocation score at the time of transplantation and by the underlying lung disease.
It is reassuring to see that the two studies published so far that accounted for the course of patient disease after placement on a wait list reached essentially the same conclusions: Most of the patients experienced a survival benefit from lung transplantation.
Dr. Gabriel Thabut is from the service de pneumologie B and transplantation pulmonaire at the University of Paris. These comments are taken from an accompanying editorial (Ann Am Thorac Soc. 2017;14:163-4. doi: 10.1513/AnnalsATS.201611-853ED). No conflicts of interest were declared.
Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.
In a study published in the February issue of the Annals of the American Thoracic Society, researchers used data from 13,040 adults listed for lung transplantation between May 2005 and September 2011 to develop a structural nested accelerated failure time model of the survival benefit of lung transplantation over time.
“A ‘structural nested model’ is [used to] compare the distribution of counterfactual residual survival if a patient were to receive a transplanted organ with the survival distribution if the patient did not receive that organ and never received one subsequently,” wrote David M. Vock, PhD, from the University of Minnesota, and coauthors.
Using this approach, they calculated that 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with transplantation. At 1 year posttransplantation, the relative survival benefit was 1.59, at 2 years it was 1.93, and at 3 years it was 2.23 (Ann Am Thorac Soc. 2017;14:172-81. doi: 10.1513/AnnalsATS.201606-507OC).
Patients’ lung allocation score at transplantation (LAS-T) – the score used to prioritize donated lungs for transplantation – had a significant impact on the survival benefit from transplantation. The relative survival benefit of transplantation increased by 59.4% as the lung allocation score increased from 30 to 35, and increased by 45.1% as the lung allocation score increased from 50 to 55.
However patients with a lung allocation score of 32.5 or less were more likely to die with a transplant than without, even over the long term, while patients with a score of 35 or more always gained a survival advantage from transplantation, even if their scores were as high as 50-100. The authors said this showed there should be no upper limit for the lung allocation score.
“It has been suggested that the LAS system may encourage patients who have clinically deteriorated to undergo transplantation even though it would be futile,” they wrote. “Our results reinforce the notion that lung transplantation should be considered an appropriate treatment option for patients with most advanced lung diseases and is expected to confer survival benefit in appropriately selected patients.”
Researchers also observed an interesting, borderline significant association between disease group and survival benefit, with individuals with obstructive lung disease showing the lowest relative survival gains and those with cystic fibrosis showing the highest. Head to head, the relative survival benefit of transplantation for those with cystic fibrosis was 54.4% greater than for those with obstructive lung disease.
Other factors such as transplant type, age, smoking, and center volume also influenced relative survival benefit. Bilateral transplants were associated with a 13.4% greater relative survival benefit, lungs from donors aged under 55 years showed a 17.9% relative survival benefit, and lungs from donors without a history of smoking showed a 10.5% increase in relative survival benefit.
However the researchers noted that their modeling focused on only the survival benefit of transplantation and did not take into account improvements in quality of life. This was likely to be particularly relevant in conditions such as chronic obstructive pulmonary disease where the quality of life benefits might justify transplantation even in the absence of a clear survival benefit.
“A comprehensive understanding of the survival benefit of lung transplantation and how that benefit varies by recipient characteristics is imperative to inform recipient selection, to justify the intensive health care resources allocated to this treatment, and to achieve an equitable allocation of donor lungs,” the researchers said.
The study was supported by the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute of Allergy and Infectious Diseases. One author declared grants and personal fees from private industry for consultation on lung transplantation. No other conflicts of interest were declared.
Nearly three-quarters of lung transplant recipients are likely to gain at least 2 years of survival, according to new research.
In a study published in the February issue of the Annals of the American Thoracic Society, researchers used data from 13,040 adults listed for lung transplantation between May 2005 and September 2011 to develop a structural nested accelerated failure time model of the survival benefit of lung transplantation over time.
“A ‘structural nested model’ is [used to] compare the distribution of counterfactual residual survival if a patient were to receive a transplanted organ with the survival distribution if the patient did not receive that organ and never received one subsequently,” wrote David M. Vock, PhD, from the University of Minnesota, and coauthors.
Using this approach, they calculated that 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with transplantation. At 1 year posttransplantation, the relative survival benefit was 1.59, at 2 years it was 1.93, and at 3 years it was 2.23 (Ann Am Thorac Soc. 2017;14:172-81. doi: 10.1513/AnnalsATS.201606-507OC).
Patients’ lung allocation score at transplantation (LAS-T) – the score used to prioritize donated lungs for transplantation – had a significant impact on the survival benefit from transplantation. The relative survival benefit of transplantation increased by 59.4% as the lung allocation score increased from 30 to 35, and increased by 45.1% as the lung allocation score increased from 50 to 55.
However patients with a lung allocation score of 32.5 or less were more likely to die with a transplant than without, even over the long term, while patients with a score of 35 or more always gained a survival advantage from transplantation, even if their scores were as high as 50-100. The authors said this showed there should be no upper limit for the lung allocation score.
“It has been suggested that the LAS system may encourage patients who have clinically deteriorated to undergo transplantation even though it would be futile,” they wrote. “Our results reinforce the notion that lung transplantation should be considered an appropriate treatment option for patients with most advanced lung diseases and is expected to confer survival benefit in appropriately selected patients.”
Researchers also observed an interesting, borderline significant association between disease group and survival benefit, with individuals with obstructive lung disease showing the lowest relative survival gains and those with cystic fibrosis showing the highest. Head to head, the relative survival benefit of transplantation for those with cystic fibrosis was 54.4% greater than for those with obstructive lung disease.
Other factors such as transplant type, age, smoking, and center volume also influenced relative survival benefit. Bilateral transplants were associated with a 13.4% greater relative survival benefit, lungs from donors aged under 55 years showed a 17.9% relative survival benefit, and lungs from donors without a history of smoking showed a 10.5% increase in relative survival benefit.
However the researchers noted that their modeling focused on only the survival benefit of transplantation and did not take into account improvements in quality of life. This was likely to be particularly relevant in conditions such as chronic obstructive pulmonary disease where the quality of life benefits might justify transplantation even in the absence of a clear survival benefit.
“A comprehensive understanding of the survival benefit of lung transplantation and how that benefit varies by recipient characteristics is imperative to inform recipient selection, to justify the intensive health care resources allocated to this treatment, and to achieve an equitable allocation of donor lungs,” the researchers said.
The study was supported by the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute of Allergy and Infectious Diseases. One author declared grants and personal fees from private industry for consultation on lung transplantation. No other conflicts of interest were declared.
FROM ANNALS OF THE AMERICAN THORACIC SOCIETY
Key clinical point: Nearly three-quarters of lung transplant recipients are predicted to achieve a 2-year survival benefit with transplantation.
Major finding: Research suggests 73.8% of transplant recipients are likely to achieve a 2-year survival benefit with transplantation.
Data source: A structural nested accelerated failure time model of the survival benefit of lung transplantation using data from 13,040 adults listed for lung transplantation.
Disclosures: The study was supported by the National Heart, Lung, and Blood Institute; the National Cancer Institute; and the National Institute of Allergy and Infectious Diseases. One author declared grants and personal fees from private industry for consultation on lung transplantation. No other conflicts of interest were declared.
Factors may flag kids at high risk for C. difficile recurrence
The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.
In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.
Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.
This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.
The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.
In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.
Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.
This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.
The identification of risk factors associated with recurrent Clostridium difficile infection (rCDI) might allow early recognition of those children at highest risk, said Dr. Maribeth Nicholson of Vanderbilt University, Nashville, Tenn., and her associates.
In a small study, results showed that fecal lactoferrin, calprotectin, and interleukin-8 (IL-8) should be further studied to determine their value in predicting the risk of rCDI in children.
Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. There were higher initial median fecal lactoferrin, calprotectin, and IL-8 values in those with recurrent disease, although there was a notably wide range of results in these patients. These values were lower in children with malignancy, the investigators said.
This study was partially supported by the Thrasher Early Career Award and two National Institutes of Health grants. The investigators had no relevant financial disclosures.
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
Adverse childhood experiences
Adverse childhood experiences (ACEs) are the traumatic experiences in a person’s life occurring before the age of 18 years that the person remembers as an adult and that have consequences on a diverse set of outcomes. ACEs include physical abuse, sexual abuse, emotional abuse, mental illness of a household member, problematic drinking or alcoholism of a household member, illegal street or prescription drug use by a household member, divorce or separation of a parent, domestic violence toward a parent, and incarceration of a household member. Each of these experiences before the age of 18 years increases the likelihood of not only adulthood depression, suicide, and substance use disorders, but also a range of nonpsychiatric outcomes such as heart disease and chronic lung disease.
Case summary
Ellie is a 16-year-old girl with a past history of ADHD and oppositionality who arrives on her own in a walk-in clinic to be seen for a sports physical. Ellie has been generally healthy and was previously on a stable medical regimen of methylphenidate but has not been taking it for about 1 year. The oppositionality that she previously experienced in her early school-age years has slowly decreased. She generally does well in school and is in several clubs. In the course of the history, Ellie reveals that her mother’s depression has been worse lately to the point where her mother has resumed her drinking and illegal opiate use. You discuss safety with Ellie, and she reveals that, while she has never been threatened or injured, there has been domestic violence in the home that Ellie felt responsible to try to stop by calling the police. This led to the one and only time that Ellie was physically struck. Her father is now incarcerated, and Ellie feels guilty. After a discussion with Ellie, you report this situation to social services, who already has the case on file. Ellie’s mental status exam, including a thorough examination of symptoms of mood disorders, anxiety, substance use, and PTSD, is within normal limits.
Case discussion
Ellie has suffered a set of ACEs. Specifically, her mother has a mental illness, has a drinking problem, and uses illegal drugs; Ellie has witnessed domestic violence toward her mother, has a family member who is incarcerated, and has suffered from physical abuse. This ACEs score of 6 puts her at markedly increased risk for multiple psychiatric and nonpsychiatric medical outcomes. Individuals with scores of 4 or above on the simple ACEs questionnaire have demonstrated a 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempts. Further, studies have shown a twofold to fourfold increase in smoking, poor self-rated health, increased numbers of sexual partners and sexually transmitted disease, and 1.4- to 1.6-fold increase in physical inactivity and severe obesity (Am J Prev Med. 1998 May;14[4]:245-58). In Ellie’s case, her history of ADHD and family history of substance use puts her at even further increased risk for later substance use disorders.
While there is no pharmacotherapy or psychotherapy specific to the treatment of having suffered adversity, it is critical for the clinician to note her increased risk. Ellie would be an individual for whom health promotion and prevention would be critical. It is excellent that she is exercising and participating in sports, which appear to be protective. Careful counseling and follow-up with regard to her increased risk for psychiatric and nonpsychiatric disorders is paramount.
Dr. Althoff is associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Email him at [email protected].
Adverse childhood experiences (ACEs) are the traumatic experiences in a person’s life occurring before the age of 18 years that the person remembers as an adult and that have consequences on a diverse set of outcomes. ACEs include physical abuse, sexual abuse, emotional abuse, mental illness of a household member, problematic drinking or alcoholism of a household member, illegal street or prescription drug use by a household member, divorce or separation of a parent, domestic violence toward a parent, and incarceration of a household member. Each of these experiences before the age of 18 years increases the likelihood of not only adulthood depression, suicide, and substance use disorders, but also a range of nonpsychiatric outcomes such as heart disease and chronic lung disease.
Case summary
Ellie is a 16-year-old girl with a past history of ADHD and oppositionality who arrives on her own in a walk-in clinic to be seen for a sports physical. Ellie has been generally healthy and was previously on a stable medical regimen of methylphenidate but has not been taking it for about 1 year. The oppositionality that she previously experienced in her early school-age years has slowly decreased. She generally does well in school and is in several clubs. In the course of the history, Ellie reveals that her mother’s depression has been worse lately to the point where her mother has resumed her drinking and illegal opiate use. You discuss safety with Ellie, and she reveals that, while she has never been threatened or injured, there has been domestic violence in the home that Ellie felt responsible to try to stop by calling the police. This led to the one and only time that Ellie was physically struck. Her father is now incarcerated, and Ellie feels guilty. After a discussion with Ellie, you report this situation to social services, who already has the case on file. Ellie’s mental status exam, including a thorough examination of symptoms of mood disorders, anxiety, substance use, and PTSD, is within normal limits.
Case discussion
Ellie has suffered a set of ACEs. Specifically, her mother has a mental illness, has a drinking problem, and uses illegal drugs; Ellie has witnessed domestic violence toward her mother, has a family member who is incarcerated, and has suffered from physical abuse. This ACEs score of 6 puts her at markedly increased risk for multiple psychiatric and nonpsychiatric medical outcomes. Individuals with scores of 4 or above on the simple ACEs questionnaire have demonstrated a 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempts. Further, studies have shown a twofold to fourfold increase in smoking, poor self-rated health, increased numbers of sexual partners and sexually transmitted disease, and 1.4- to 1.6-fold increase in physical inactivity and severe obesity (Am J Prev Med. 1998 May;14[4]:245-58). In Ellie’s case, her history of ADHD and family history of substance use puts her at even further increased risk for later substance use disorders.
While there is no pharmacotherapy or psychotherapy specific to the treatment of having suffered adversity, it is critical for the clinician to note her increased risk. Ellie would be an individual for whom health promotion and prevention would be critical. It is excellent that she is exercising and participating in sports, which appear to be protective. Careful counseling and follow-up with regard to her increased risk for psychiatric and nonpsychiatric disorders is paramount.
Dr. Althoff is associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Email him at [email protected].
Adverse childhood experiences (ACEs) are the traumatic experiences in a person’s life occurring before the age of 18 years that the person remembers as an adult and that have consequences on a diverse set of outcomes. ACEs include physical abuse, sexual abuse, emotional abuse, mental illness of a household member, problematic drinking or alcoholism of a household member, illegal street or prescription drug use by a household member, divorce or separation of a parent, domestic violence toward a parent, and incarceration of a household member. Each of these experiences before the age of 18 years increases the likelihood of not only adulthood depression, suicide, and substance use disorders, but also a range of nonpsychiatric outcomes such as heart disease and chronic lung disease.
Case summary
Ellie is a 16-year-old girl with a past history of ADHD and oppositionality who arrives on her own in a walk-in clinic to be seen for a sports physical. Ellie has been generally healthy and was previously on a stable medical regimen of methylphenidate but has not been taking it for about 1 year. The oppositionality that she previously experienced in her early school-age years has slowly decreased. She generally does well in school and is in several clubs. In the course of the history, Ellie reveals that her mother’s depression has been worse lately to the point where her mother has resumed her drinking and illegal opiate use. You discuss safety with Ellie, and she reveals that, while she has never been threatened or injured, there has been domestic violence in the home that Ellie felt responsible to try to stop by calling the police. This led to the one and only time that Ellie was physically struck. Her father is now incarcerated, and Ellie feels guilty. After a discussion with Ellie, you report this situation to social services, who already has the case on file. Ellie’s mental status exam, including a thorough examination of symptoms of mood disorders, anxiety, substance use, and PTSD, is within normal limits.
Case discussion
Ellie has suffered a set of ACEs. Specifically, her mother has a mental illness, has a drinking problem, and uses illegal drugs; Ellie has witnessed domestic violence toward her mother, has a family member who is incarcerated, and has suffered from physical abuse. This ACEs score of 6 puts her at markedly increased risk for multiple psychiatric and nonpsychiatric medical outcomes. Individuals with scores of 4 or above on the simple ACEs questionnaire have demonstrated a 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempts. Further, studies have shown a twofold to fourfold increase in smoking, poor self-rated health, increased numbers of sexual partners and sexually transmitted disease, and 1.4- to 1.6-fold increase in physical inactivity and severe obesity (Am J Prev Med. 1998 May;14[4]:245-58). In Ellie’s case, her history of ADHD and family history of substance use puts her at even further increased risk for later substance use disorders.
While there is no pharmacotherapy or psychotherapy specific to the treatment of having suffered adversity, it is critical for the clinician to note her increased risk. Ellie would be an individual for whom health promotion and prevention would be critical. It is excellent that she is exercising and participating in sports, which appear to be protective. Careful counseling and follow-up with regard to her increased risk for psychiatric and nonpsychiatric disorders is paramount.
Dr. Althoff is associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Email him at [email protected].
Prednisone reduces TB-IRIS risk
SEATTLE – In patients coinfected with HIV and tuberculosis, addition of prednisone to an antiretroviral therapy (ART)/TB regimen significantly reduced the incidence of tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS).
The study showed a reduction of incidence of TB-IRIS – a worsening of the inflammatory elements of tuberculosis that often occurs within a few weeks of starting ART – in the prednisone group, with no sign of adverse events associated with immunosuppression. That safety profile “gives us the reassurance that this is something that could be scaled up. It’s effective but it’s also safe,” said Graeme Meintjes, MD, PhD, professor of medicine at the University of Cape Town, South Africa.
TB-IRIS occurs in 18% of patients undergoing ART/TB regimens, and 25% of these patients wind up in the hospital (Future Microbiol. 2015;10[6]:1077-99).
Ironically, TB-IRIS is of increasing concern because of improved treatment strategies. Clinical trials have shown that, in patients with low CD4 counts, TB mortality is decreased by about 20% if ART is started within 2 weeks of initiation of TB treatment. But when ART is started so soon after TB therapy, patients with low CD4 counts are at about a twofold increased risk of TB-IRIS (Ann Intern Med. 2015;163[1]:32-9).
“That brought into focus the need for an intervention to prevent this complication,” said Dr. Meintjes, who presented the study at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
There were concerns that prednisone could put HIV patients at greater risk of opportunistic infections such as Kaposi’s sarcoma, although Dr. Meintjes noted that those risks were seen in a context of patients who were not taking ART. His team also showed in a previous study (AIDS. 2010;24:2381-90) that prednisone reduced duration of symptoms and hospitalization in TB-IRIS, with no increase in serious infections.
The researchers randomized 240 patients to receive prednisone (40 mg/day for 2 weeks, then 20 mg/day for 2 weeks) within 48 hours of starting ART. All patients started ART within 30 days of starting TB treatment, and had a CD4 count of 100 or fewer cells/microL.
Excluded patients included those with rifampicin resistance, neurobiological tuberculosis, Kaposi’s sarcoma, or hepatitis B, and those who weren’t on the standard first line TB treatment because they couldn’t tolerate it. Patients were also excluded if they had a poor clinical response to TB treatment.
Most endpoints were followed for 12 weeks, but HIV-related cancers were monitored out to 1 year.
Forty-seven percent of patients in the placebo group experienced TB-IRIS within 12 weeks, compared with 33% of patients in the prednisone group (risk ratio, 0.70; 95% confidence interval 0.51-0.96). In an open-label extension study, the researchers noted that 28% of patients who started out in the placebo arm eventually received corticosteroids to treat TB-IRIS, compared with 13% of those who started out in the prednisone arm (RR 0.47, 95% CI 0.27-0.83).
Subjects in the prednisone arm had a lower rate of grade 3 adverse events (29% vs. 45%, P = .01).
There was a similar mortality rate in both arms, and no difference in the incidence of Kaposi’s sarcoma or new-onset AIDS-defining infections.
Dr. Meintjes pointed out that patient selection is important. The trial patients were seen in the clinical setting, not sicker, hospitalized patients, and they had to be improving with TB treatment; significant comorbidities were excluded. “In those patients, prednisone was safe.”
Dr. Meintjes reported having no relevant financial disclosures.
SEATTLE – In patients coinfected with HIV and tuberculosis, addition of prednisone to an antiretroviral therapy (ART)/TB regimen significantly reduced the incidence of tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS).
The study showed a reduction of incidence of TB-IRIS – a worsening of the inflammatory elements of tuberculosis that often occurs within a few weeks of starting ART – in the prednisone group, with no sign of adverse events associated with immunosuppression. That safety profile “gives us the reassurance that this is something that could be scaled up. It’s effective but it’s also safe,” said Graeme Meintjes, MD, PhD, professor of medicine at the University of Cape Town, South Africa.
TB-IRIS occurs in 18% of patients undergoing ART/TB regimens, and 25% of these patients wind up in the hospital (Future Microbiol. 2015;10[6]:1077-99).
Ironically, TB-IRIS is of increasing concern because of improved treatment strategies. Clinical trials have shown that, in patients with low CD4 counts, TB mortality is decreased by about 20% if ART is started within 2 weeks of initiation of TB treatment. But when ART is started so soon after TB therapy, patients with low CD4 counts are at about a twofold increased risk of TB-IRIS (Ann Intern Med. 2015;163[1]:32-9).
“That brought into focus the need for an intervention to prevent this complication,” said Dr. Meintjes, who presented the study at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
There were concerns that prednisone could put HIV patients at greater risk of opportunistic infections such as Kaposi’s sarcoma, although Dr. Meintjes noted that those risks were seen in a context of patients who were not taking ART. His team also showed in a previous study (AIDS. 2010;24:2381-90) that prednisone reduced duration of symptoms and hospitalization in TB-IRIS, with no increase in serious infections.
The researchers randomized 240 patients to receive prednisone (40 mg/day for 2 weeks, then 20 mg/day for 2 weeks) within 48 hours of starting ART. All patients started ART within 30 days of starting TB treatment, and had a CD4 count of 100 or fewer cells/microL.
Excluded patients included those with rifampicin resistance, neurobiological tuberculosis, Kaposi’s sarcoma, or hepatitis B, and those who weren’t on the standard first line TB treatment because they couldn’t tolerate it. Patients were also excluded if they had a poor clinical response to TB treatment.
Most endpoints were followed for 12 weeks, but HIV-related cancers were monitored out to 1 year.
Forty-seven percent of patients in the placebo group experienced TB-IRIS within 12 weeks, compared with 33% of patients in the prednisone group (risk ratio, 0.70; 95% confidence interval 0.51-0.96). In an open-label extension study, the researchers noted that 28% of patients who started out in the placebo arm eventually received corticosteroids to treat TB-IRIS, compared with 13% of those who started out in the prednisone arm (RR 0.47, 95% CI 0.27-0.83).
Subjects in the prednisone arm had a lower rate of grade 3 adverse events (29% vs. 45%, P = .01).
There was a similar mortality rate in both arms, and no difference in the incidence of Kaposi’s sarcoma or new-onset AIDS-defining infections.
Dr. Meintjes pointed out that patient selection is important. The trial patients were seen in the clinical setting, not sicker, hospitalized patients, and they had to be improving with TB treatment; significant comorbidities were excluded. “In those patients, prednisone was safe.”
Dr. Meintjes reported having no relevant financial disclosures.
SEATTLE – In patients coinfected with HIV and tuberculosis, addition of prednisone to an antiretroviral therapy (ART)/TB regimen significantly reduced the incidence of tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS).
The study showed a reduction of incidence of TB-IRIS – a worsening of the inflammatory elements of tuberculosis that often occurs within a few weeks of starting ART – in the prednisone group, with no sign of adverse events associated with immunosuppression. That safety profile “gives us the reassurance that this is something that could be scaled up. It’s effective but it’s also safe,” said Graeme Meintjes, MD, PhD, professor of medicine at the University of Cape Town, South Africa.
TB-IRIS occurs in 18% of patients undergoing ART/TB regimens, and 25% of these patients wind up in the hospital (Future Microbiol. 2015;10[6]:1077-99).
Ironically, TB-IRIS is of increasing concern because of improved treatment strategies. Clinical trials have shown that, in patients with low CD4 counts, TB mortality is decreased by about 20% if ART is started within 2 weeks of initiation of TB treatment. But when ART is started so soon after TB therapy, patients with low CD4 counts are at about a twofold increased risk of TB-IRIS (Ann Intern Med. 2015;163[1]:32-9).
“That brought into focus the need for an intervention to prevent this complication,” said Dr. Meintjes, who presented the study at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
There were concerns that prednisone could put HIV patients at greater risk of opportunistic infections such as Kaposi’s sarcoma, although Dr. Meintjes noted that those risks were seen in a context of patients who were not taking ART. His team also showed in a previous study (AIDS. 2010;24:2381-90) that prednisone reduced duration of symptoms and hospitalization in TB-IRIS, with no increase in serious infections.
The researchers randomized 240 patients to receive prednisone (40 mg/day for 2 weeks, then 20 mg/day for 2 weeks) within 48 hours of starting ART. All patients started ART within 30 days of starting TB treatment, and had a CD4 count of 100 or fewer cells/microL.
Excluded patients included those with rifampicin resistance, neurobiological tuberculosis, Kaposi’s sarcoma, or hepatitis B, and those who weren’t on the standard first line TB treatment because they couldn’t tolerate it. Patients were also excluded if they had a poor clinical response to TB treatment.
Most endpoints were followed for 12 weeks, but HIV-related cancers were monitored out to 1 year.
Forty-seven percent of patients in the placebo group experienced TB-IRIS within 12 weeks, compared with 33% of patients in the prednisone group (risk ratio, 0.70; 95% confidence interval 0.51-0.96). In an open-label extension study, the researchers noted that 28% of patients who started out in the placebo arm eventually received corticosteroids to treat TB-IRIS, compared with 13% of those who started out in the prednisone arm (RR 0.47, 95% CI 0.27-0.83).
Subjects in the prednisone arm had a lower rate of grade 3 adverse events (29% vs. 45%, P = .01).
There was a similar mortality rate in both arms, and no difference in the incidence of Kaposi’s sarcoma or new-onset AIDS-defining infections.
Dr. Meintjes pointed out that patient selection is important. The trial patients were seen in the clinical setting, not sicker, hospitalized patients, and they had to be improving with TB treatment; significant comorbidities were excluded. “In those patients, prednisone was safe.”
Dr. Meintjes reported having no relevant financial disclosures.
AT CROI
Key clinical point:
Major finding: Forty-seven percent of placebo patients experienced TB-IRIS within 12 weeks, compared with 33% of patients in the prednisone group.
Data source: Randomized, placebo-controlled trial of 240 patients.
Disclosures: Dr. Meintjes reported having no relevant financial disclosures.
Costs prompt changes in drug use for cancer survivors
A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.
The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.
However, this was only true for non-elderly individuals.
There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.
Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.
The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.
The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.
Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).
“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.
On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.
The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.
The researchers said these results could be explained by uniform healthcare coverage through Medicare.
The team also said their findings may have significant policy implications.
“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.
“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.” 
A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.
The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.
However, this was only true for non-elderly individuals.
There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.
Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.
The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.
The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.
Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).
“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.
On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.
The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.
The researchers said these results could be explained by uniform healthcare coverage through Medicare.
The team also said their findings may have significant policy implications.
“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.
“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”
A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.
The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.
However, this was only true for non-elderly individuals.
There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.
Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.
The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.
The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.
Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).
“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.
On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.
The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.
The researchers said these results could be explained by uniform healthcare coverage through Medicare.
The team also said their findings may have significant policy implications.
“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.
“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”
FDA grants priority review to ALL drug
The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
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’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.
The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.
About inotuzumab ozogamicin
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy. 
The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
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’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.
The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.
About inotuzumab ozogamicin
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.
The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
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’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.
The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.
About inotuzumab ozogamicin
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.
The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.
The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.
The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.
The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).
Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).
The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).
The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).
Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).
Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.
There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.