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State regulations for tattoo facilities increased blood donor pools
SAN DIEGO – Tattoos are rapidly moving into mainstream America, and as more states regulate tattoo facilities, persons with tattoos can be blood donors without compromising patient safety, Mary Townsend of Blood Systems Inc. reported at the annual meeting of the American Association of Blood Banks.
“Two big states – Arizona and California – were added to the list of approved states, and we had a gain of 2,216 donors in California during a 3-month period and a gain of 4,035 donors in Arizona over 4 months,” Ms. Townsend said.
Both the AABB and the Food and Drug Administration require a 12-month deferral of donors after they have received tattoos using nonsterile needles or reusable ink. The FDA’s current 2015 guidance also states that tattooed donors can give plasma as soon as the inked area has healed if they reside in a state with applied inspections and licenses for tattoo facilities, and if a sterile needle and ink were used.
Blood Systems monitors state regulations to see if they require tattoo establishments to be licensed and require the use of sterile needles and non-reusable ink. To be considered an approved state, the regulations have to be statewide, covering all jurisdictions.
In the study, Ms. Townsend and her colleagues compared the rates of donors who were deferred before and after Arizona and California were added to the list of approved states, to determine the potential gain in donors with changes in state tattoo licensing regulations.
They analyzed blood centers in California and Arizona before and after implementation of state tattoo regulations, and also screened individuals who had received tattoos in those states with the question: “In the past 12 months have you had a tattoo?” and if the answer was ‘yes,’ if the tattoo was applied by a state regulated facility.
For California, they compared two periods – 3 months before regulations were implemented (February to April of 2015) and 3 months after (February to April of 2016) regulations were implemented. For Arizona, they selected a 4-month period (December 2015 to March 2016) and 4 months afterward (December 2016 to March 2017).
A higher proportion of donors who came to centers to donate blood admitted to having gotten a tattoo within the last 12 months in the postregulatory period in both states. The increase in donors occurred immediately following the addition of both states to the Acceptable States List. Accepted donors increased 13-fold in California and 3-fold in Arizona. The absolute number of accepted donors with tattoos rose from 13 to 567 in California and from 151 to 1,496 in Arizona, which represented an annual potential gain of 2,216 and 4,035 additional blood donations.
For blood donors who received a tattoo in a regulated state, blood donations were reviewed for the presence of infectious disease markers including HIV, hepatitis B, and hepatitis C. All donors who had received a tattoo in a regulated state tested negative for HIV, HBV, and HCV.
“Roughly one in three people (in the United States) have a tattoo and, of those, about 70% have more than one tattoo. The bottom line is that 45 million Americans have at least one tattoo,” she said. As state regulations adhere to guidelines regarding tattoos and blood donation, the pool of donors increases.
SAN DIEGO – Tattoos are rapidly moving into mainstream America, and as more states regulate tattoo facilities, persons with tattoos can be blood donors without compromising patient safety, Mary Townsend of Blood Systems Inc. reported at the annual meeting of the American Association of Blood Banks.
“Two big states – Arizona and California – were added to the list of approved states, and we had a gain of 2,216 donors in California during a 3-month period and a gain of 4,035 donors in Arizona over 4 months,” Ms. Townsend said.
Both the AABB and the Food and Drug Administration require a 12-month deferral of donors after they have received tattoos using nonsterile needles or reusable ink. The FDA’s current 2015 guidance also states that tattooed donors can give plasma as soon as the inked area has healed if they reside in a state with applied inspections and licenses for tattoo facilities, and if a sterile needle and ink were used.
Blood Systems monitors state regulations to see if they require tattoo establishments to be licensed and require the use of sterile needles and non-reusable ink. To be considered an approved state, the regulations have to be statewide, covering all jurisdictions.
In the study, Ms. Townsend and her colleagues compared the rates of donors who were deferred before and after Arizona and California were added to the list of approved states, to determine the potential gain in donors with changes in state tattoo licensing regulations.
They analyzed blood centers in California and Arizona before and after implementation of state tattoo regulations, and also screened individuals who had received tattoos in those states with the question: “In the past 12 months have you had a tattoo?” and if the answer was ‘yes,’ if the tattoo was applied by a state regulated facility.
For California, they compared two periods – 3 months before regulations were implemented (February to April of 2015) and 3 months after (February to April of 2016) regulations were implemented. For Arizona, they selected a 4-month period (December 2015 to March 2016) and 4 months afterward (December 2016 to March 2017).
A higher proportion of donors who came to centers to donate blood admitted to having gotten a tattoo within the last 12 months in the postregulatory period in both states. The increase in donors occurred immediately following the addition of both states to the Acceptable States List. Accepted donors increased 13-fold in California and 3-fold in Arizona. The absolute number of accepted donors with tattoos rose from 13 to 567 in California and from 151 to 1,496 in Arizona, which represented an annual potential gain of 2,216 and 4,035 additional blood donations.
For blood donors who received a tattoo in a regulated state, blood donations were reviewed for the presence of infectious disease markers including HIV, hepatitis B, and hepatitis C. All donors who had received a tattoo in a regulated state tested negative for HIV, HBV, and HCV.
“Roughly one in three people (in the United States) have a tattoo and, of those, about 70% have more than one tattoo. The bottom line is that 45 million Americans have at least one tattoo,” she said. As state regulations adhere to guidelines regarding tattoos and blood donation, the pool of donors increases.
SAN DIEGO – Tattoos are rapidly moving into mainstream America, and as more states regulate tattoo facilities, persons with tattoos can be blood donors without compromising patient safety, Mary Townsend of Blood Systems Inc. reported at the annual meeting of the American Association of Blood Banks.
“Two big states – Arizona and California – were added to the list of approved states, and we had a gain of 2,216 donors in California during a 3-month period and a gain of 4,035 donors in Arizona over 4 months,” Ms. Townsend said.
Both the AABB and the Food and Drug Administration require a 12-month deferral of donors after they have received tattoos using nonsterile needles or reusable ink. The FDA’s current 2015 guidance also states that tattooed donors can give plasma as soon as the inked area has healed if they reside in a state with applied inspections and licenses for tattoo facilities, and if a sterile needle and ink were used.
Blood Systems monitors state regulations to see if they require tattoo establishments to be licensed and require the use of sterile needles and non-reusable ink. To be considered an approved state, the regulations have to be statewide, covering all jurisdictions.
In the study, Ms. Townsend and her colleagues compared the rates of donors who were deferred before and after Arizona and California were added to the list of approved states, to determine the potential gain in donors with changes in state tattoo licensing regulations.
They analyzed blood centers in California and Arizona before and after implementation of state tattoo regulations, and also screened individuals who had received tattoos in those states with the question: “In the past 12 months have you had a tattoo?” and if the answer was ‘yes,’ if the tattoo was applied by a state regulated facility.
For California, they compared two periods – 3 months before regulations were implemented (February to April of 2015) and 3 months after (February to April of 2016) regulations were implemented. For Arizona, they selected a 4-month period (December 2015 to March 2016) and 4 months afterward (December 2016 to March 2017).
A higher proportion of donors who came to centers to donate blood admitted to having gotten a tattoo within the last 12 months in the postregulatory period in both states. The increase in donors occurred immediately following the addition of both states to the Acceptable States List. Accepted donors increased 13-fold in California and 3-fold in Arizona. The absolute number of accepted donors with tattoos rose from 13 to 567 in California and from 151 to 1,496 in Arizona, which represented an annual potential gain of 2,216 and 4,035 additional blood donations.
For blood donors who received a tattoo in a regulated state, blood donations were reviewed for the presence of infectious disease markers including HIV, hepatitis B, and hepatitis C. All donors who had received a tattoo in a regulated state tested negative for HIV, HBV, and HCV.
“Roughly one in three people (in the United States) have a tattoo and, of those, about 70% have more than one tattoo. The bottom line is that 45 million Americans have at least one tattoo,” she said. As state regulations adhere to guidelines regarding tattoos and blood donation, the pool of donors increases.
AT AABB 2017
Key clinical point:
Major finding: The absolute number of accepted donors with tattoos rose from 13 to 567 in California and from 151 to 1,496 in Arizona, which represented an annual potential gain of 2,216 and 4,035 additional blood donations.
Data source: An analysis of blood centers in California and Arizona before and after state tattoo regulations were implemented.
Disclosures: Dr. Townsend has no disclosures.
Stroke cognitive outcomes found worse in Mexican Americans
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
SAN DIEGO – A new analysis shows that Mexican Americans (MAs) have worse cognitive outcomes a year after having a stroke than do non-Hispanic whites (NHWs).
The findings, which show that MAs had a mean score of 86 on the Modified Mini-Mental State Examination (3MSE; range: 0-100), compared with 92 for NHWs, come from a prospective study of MAs and NHWs in Corpus Christi, Texas, where both populations have long-established residencies.
After controlling for all factors, the researchers found a difference of –6.73 (95% confidence interval, –3.88 to –9.57; P less than .001).
“The Mexican-American population is growing quickly and aging. The cost of stroke-related cognitive impairment is high for patient, family, and society. Efforts to combat stroke-related cognitive decline are critical,” said Dr. Morgenstern, professor of neurology and epidemiology at the University of Michigan, Ann Arbor.
The study grew out of the Brain Attack Surveillance in Corpus Christi (BASIC) Project, which began in 1999 and is funded until 2019. It is the only ongoing stroke surveillance program that focuses on Mexican Americans, who comprise the largest segment of Hispanic Americans.
The researchers analyzed data encompassing all stroke patients in the BASIC Project from October 2014 through January 2016 (n = 227). They analyzed cognitive outcome data from 3 months, 6 months, and 12 months. MAs were younger on average than NHWs (median age 66 vs. 70; P = .018), and were more likely to have diabetes (54% vs. 36%; P less than .001). They were less likely to have atrial fibrillation (13% vs. 20%; P = .025).
At 12 months, MAs had a lower median 3MSE score of 86 (interquartile range, 73-93, compared with 92 in NHWs (IQR, 83-96; P less than .001). As the researchers adjusted for additional factors, the discrepancy became larger. Adjustment for age and sex revealed a difference of 6.88 (95% confidence interval, 4.15-9.60). Additional adjustment for prestroke condition showed a difference of 7.04. Additional adjustment for insurance led to the same differential of 7.04. Adjustment for diabetes and comorbidities pushed the difference to 7.11. Adjustment for stroke severity (National Institutes of Health Stroke Scale) revealed a difference of 6.73 (P less than .001).
Asked if the results were surprising, Dr. Morgenstern replied: “I think it’s always surprising to see one population of U.S. citizens who have more disease or a worse outcome than another when it’s not explained by the many possible factors we considered.” He also called for additional studies of cognitive dysfunction in Hispanic communities in other forms of dementia, such as Alzheimer’s disease and vascular dementia. “There’s very little of that,” he said.
The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
AT ANA 2017
Key clinical point: In an analysis, cognitive outcomes were worse in Mexican-American stroke survivors despite researchers’ controlling for many factors.
Major finding: At 12 months, Mexican Americans scored 6 points lower on the Modified Mini-Mental State Examination compared with non-Hispanic whites.
Data source: Prospective analysis of 227 stroke patients in Corpus Christi, Texas.
Disclosures: The National Institutes of Health funded the study. Dr. Morgenstern reported having no financial disclosures.
Patients prefer higher dose of levothyroxine despite lack of objective benefit
VICTORIA, B.C. – Patient perception plays a large role in subjective benefit of levothyroxine therapy for hypothyroidism, suggests a double-blind randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Mood, cognition, and quality of life (QoL) did not differ whether patients’ levothyroxine dose was adjusted to achieve thyroid-stimulating hormone (TSH) levels in the low-normal, high-normal, or mildly elevated range. But despite this lack of objective benefit, the large majority of patients preferred levothyroxine doses that they perceived to be higher – whether they actually were or not.
The study was not restricted to certain groups who might have a better response to higher levothyroxine dose, she acknowledged. Two such groups are patients with more symptoms (although volunteering for the study suggested dissatisfaction with symptom control) and patients with low tri-iodothyronine (T3) levels (although about half of patients had low baseline levels).
“We encourage further research in older subjects, men, and subjects with specific symptoms, low T3 levels, or functional polymorphisms in thyroid-relevant genes,” Dr. Samuels said. “These are really difficult, expensive studies to do, and if we are going to have any hope of getting them funded and doing them, I think that we have to be much more targeted.”
One of the session co-chairs, Catherine A. Dinauer, MD, a pediatric endocrinologist and clinician at the Yale Pediatric Thyroid Center, New Haven, Conn., commented, “I think these are really interesting data because there’s this sense among patients that their dose really affects how they feel, and this is essentially turning that on its head. It’s not really clear, then, why are these patients still maybe not feeling well.”
“It will be interesting to see more data on this and ... more about this business of checking T3 levels. Do we need to supplement with T3? I think we really don’t know that, especially in kids, but even in adults,” she added.
The other session co-chair, Yaron Tomer, MD, chair of the department of medicine and the Anita and Jack Saltz Chair in Diabetes Research at the Montefiore Medical Center, Bronx, N.Y., commented, “I think this study confirmed what a lot of us feel, that there is a lot of placebo effect when you treat in different ways to optimize the TSH or give T3.”
Other data reported in the session provide a possible explanation for the lack of benefit of adjusting pharmacologic therapy, suggesting that the volumes of various brain structures change with perturbations of thyroid function, he noted. “There might be true changes in the brain that affect how the patients feel. So these patients may truly not feel well. It’s just that we can’t fix it by adjusting the TSH level to very narrow margins or by adding T3,” he said.
Study details
“It is well known that overt hypothyroidism interferes with mood and a number of cognitive functions. However, neurocognitive effects of variations in thyroid function within the reference range and in mild or subclinical hypothyroidism are less clear,” Dr. Samuels noted, giving some background to the research.
“Observational studies of this question have tended to be negative but have often included less sensitive global screening tests of cognition. There are very few small-scale interventional studies,” she continued. “In the absence of conclusive data, many patients with mild hypothyroidism are started on levothyroxine to treat nonspecific quality of life, mood, or cognitive symptoms, and many additional treated patients request increased levothyroxine doses due to persistence of these symptoms.”
Dr. Samuels and her coinvestigators enrolled in the trial 138 hypothyroid but otherwise healthy patients who had been on a stable dose of levothyroxine (Synthroid and others) alone for at least 3 months and had normal TSH levels.
The patients were randomized to three groups in which clinicians adjusted levothyroxine dose every 6 weeks in blinded fashion to achieve different target TSH levels: low-normal TSH (0.34-2.50 mU/L), high-normal TSH (2.51-5.60 mU/L), or mildly elevated TSH (5.60-12.0 mU/L). Patients completed a battery of assessments at baseline and again at 6 months.
Main results confirmed that TSH targets were generally achieved, with significantly different mean TSH levels in the low-normal group (1.34 mU/L), high-normal group (3.74 mU/L), and mildly elevated group (9.74 mU/L) (P less than .05).
In crude analyses, results differed significantly across groups for only two of the dozens of measures of mood, cognition, and QoL assessed: bodily pain (26%, 11%, and 34% of patients reporting a high pain level in the low-normal, high-normal, and mildly elevated TSH groups, respectively; P = .03) and working memory on the N-Back test (86%, 58%, and 75% with a 1-back result; P = .002). However, there were no significant differences for any of the measures when analyses were repeated with statistical correction for multiple comparisons.
At the end of the study, patients were unable to say with any accuracy say whether they were receiving a dose of levothyroxine that was higher than, lower than, or unchanged from their baseline dose (P = .55 for actual vs. perceived).
However, patients preferred what they perceived to be a higher dose (P less than .001 for preferred vs. perceived). In the group perceiving their end-of-study dose was higher, the majority of patients (68%) preferred that dose, and in the group perceiving their end-of-study dose was lower, most (96%) preferred their baseline dose.
The sample size may not have been adequate to detect very small effects of changes in levothyroxine dose, acknowledged Dr. Samuels, who disclosed that she had no relevant conflicts of interest. Additionally, patients were predominantly female and younger, and heterogeneous with respect to thyroid diagnosis and length of levothyroxine therapy.
VICTORIA, B.C. – Patient perception plays a large role in subjective benefit of levothyroxine therapy for hypothyroidism, suggests a double-blind randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Mood, cognition, and quality of life (QoL) did not differ whether patients’ levothyroxine dose was adjusted to achieve thyroid-stimulating hormone (TSH) levels in the low-normal, high-normal, or mildly elevated range. But despite this lack of objective benefit, the large majority of patients preferred levothyroxine doses that they perceived to be higher – whether they actually were or not.
The study was not restricted to certain groups who might have a better response to higher levothyroxine dose, she acknowledged. Two such groups are patients with more symptoms (although volunteering for the study suggested dissatisfaction with symptom control) and patients with low tri-iodothyronine (T3) levels (although about half of patients had low baseline levels).
“We encourage further research in older subjects, men, and subjects with specific symptoms, low T3 levels, or functional polymorphisms in thyroid-relevant genes,” Dr. Samuels said. “These are really difficult, expensive studies to do, and if we are going to have any hope of getting them funded and doing them, I think that we have to be much more targeted.”
One of the session co-chairs, Catherine A. Dinauer, MD, a pediatric endocrinologist and clinician at the Yale Pediatric Thyroid Center, New Haven, Conn., commented, “I think these are really interesting data because there’s this sense among patients that their dose really affects how they feel, and this is essentially turning that on its head. It’s not really clear, then, why are these patients still maybe not feeling well.”
“It will be interesting to see more data on this and ... more about this business of checking T3 levels. Do we need to supplement with T3? I think we really don’t know that, especially in kids, but even in adults,” she added.
The other session co-chair, Yaron Tomer, MD, chair of the department of medicine and the Anita and Jack Saltz Chair in Diabetes Research at the Montefiore Medical Center, Bronx, N.Y., commented, “I think this study confirmed what a lot of us feel, that there is a lot of placebo effect when you treat in different ways to optimize the TSH or give T3.”
Other data reported in the session provide a possible explanation for the lack of benefit of adjusting pharmacologic therapy, suggesting that the volumes of various brain structures change with perturbations of thyroid function, he noted. “There might be true changes in the brain that affect how the patients feel. So these patients may truly not feel well. It’s just that we can’t fix it by adjusting the TSH level to very narrow margins or by adding T3,” he said.
Study details
“It is well known that overt hypothyroidism interferes with mood and a number of cognitive functions. However, neurocognitive effects of variations in thyroid function within the reference range and in mild or subclinical hypothyroidism are less clear,” Dr. Samuels noted, giving some background to the research.
“Observational studies of this question have tended to be negative but have often included less sensitive global screening tests of cognition. There are very few small-scale interventional studies,” she continued. “In the absence of conclusive data, many patients with mild hypothyroidism are started on levothyroxine to treat nonspecific quality of life, mood, or cognitive symptoms, and many additional treated patients request increased levothyroxine doses due to persistence of these symptoms.”
Dr. Samuels and her coinvestigators enrolled in the trial 138 hypothyroid but otherwise healthy patients who had been on a stable dose of levothyroxine (Synthroid and others) alone for at least 3 months and had normal TSH levels.
The patients were randomized to three groups in which clinicians adjusted levothyroxine dose every 6 weeks in blinded fashion to achieve different target TSH levels: low-normal TSH (0.34-2.50 mU/L), high-normal TSH (2.51-5.60 mU/L), or mildly elevated TSH (5.60-12.0 mU/L). Patients completed a battery of assessments at baseline and again at 6 months.
Main results confirmed that TSH targets were generally achieved, with significantly different mean TSH levels in the low-normal group (1.34 mU/L), high-normal group (3.74 mU/L), and mildly elevated group (9.74 mU/L) (P less than .05).
In crude analyses, results differed significantly across groups for only two of the dozens of measures of mood, cognition, and QoL assessed: bodily pain (26%, 11%, and 34% of patients reporting a high pain level in the low-normal, high-normal, and mildly elevated TSH groups, respectively; P = .03) and working memory on the N-Back test (86%, 58%, and 75% with a 1-back result; P = .002). However, there were no significant differences for any of the measures when analyses were repeated with statistical correction for multiple comparisons.
At the end of the study, patients were unable to say with any accuracy say whether they were receiving a dose of levothyroxine that was higher than, lower than, or unchanged from their baseline dose (P = .55 for actual vs. perceived).
However, patients preferred what they perceived to be a higher dose (P less than .001 for preferred vs. perceived). In the group perceiving their end-of-study dose was higher, the majority of patients (68%) preferred that dose, and in the group perceiving their end-of-study dose was lower, most (96%) preferred their baseline dose.
The sample size may not have been adequate to detect very small effects of changes in levothyroxine dose, acknowledged Dr. Samuels, who disclosed that she had no relevant conflicts of interest. Additionally, patients were predominantly female and younger, and heterogeneous with respect to thyroid diagnosis and length of levothyroxine therapy.
VICTORIA, B.C. – Patient perception plays a large role in subjective benefit of levothyroxine therapy for hypothyroidism, suggests a double-blind randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Mood, cognition, and quality of life (QoL) did not differ whether patients’ levothyroxine dose was adjusted to achieve thyroid-stimulating hormone (TSH) levels in the low-normal, high-normal, or mildly elevated range. But despite this lack of objective benefit, the large majority of patients preferred levothyroxine doses that they perceived to be higher – whether they actually were or not.
The study was not restricted to certain groups who might have a better response to higher levothyroxine dose, she acknowledged. Two such groups are patients with more symptoms (although volunteering for the study suggested dissatisfaction with symptom control) and patients with low tri-iodothyronine (T3) levels (although about half of patients had low baseline levels).
“We encourage further research in older subjects, men, and subjects with specific symptoms, low T3 levels, or functional polymorphisms in thyroid-relevant genes,” Dr. Samuels said. “These are really difficult, expensive studies to do, and if we are going to have any hope of getting them funded and doing them, I think that we have to be much more targeted.”
One of the session co-chairs, Catherine A. Dinauer, MD, a pediatric endocrinologist and clinician at the Yale Pediatric Thyroid Center, New Haven, Conn., commented, “I think these are really interesting data because there’s this sense among patients that their dose really affects how they feel, and this is essentially turning that on its head. It’s not really clear, then, why are these patients still maybe not feeling well.”
“It will be interesting to see more data on this and ... more about this business of checking T3 levels. Do we need to supplement with T3? I think we really don’t know that, especially in kids, but even in adults,” she added.
The other session co-chair, Yaron Tomer, MD, chair of the department of medicine and the Anita and Jack Saltz Chair in Diabetes Research at the Montefiore Medical Center, Bronx, N.Y., commented, “I think this study confirmed what a lot of us feel, that there is a lot of placebo effect when you treat in different ways to optimize the TSH or give T3.”
Other data reported in the session provide a possible explanation for the lack of benefit of adjusting pharmacologic therapy, suggesting that the volumes of various brain structures change with perturbations of thyroid function, he noted. “There might be true changes in the brain that affect how the patients feel. So these patients may truly not feel well. It’s just that we can’t fix it by adjusting the TSH level to very narrow margins or by adding T3,” he said.
Study details
“It is well known that overt hypothyroidism interferes with mood and a number of cognitive functions. However, neurocognitive effects of variations in thyroid function within the reference range and in mild or subclinical hypothyroidism are less clear,” Dr. Samuels noted, giving some background to the research.
“Observational studies of this question have tended to be negative but have often included less sensitive global screening tests of cognition. There are very few small-scale interventional studies,” she continued. “In the absence of conclusive data, many patients with mild hypothyroidism are started on levothyroxine to treat nonspecific quality of life, mood, or cognitive symptoms, and many additional treated patients request increased levothyroxine doses due to persistence of these symptoms.”
Dr. Samuels and her coinvestigators enrolled in the trial 138 hypothyroid but otherwise healthy patients who had been on a stable dose of levothyroxine (Synthroid and others) alone for at least 3 months and had normal TSH levels.
The patients were randomized to three groups in which clinicians adjusted levothyroxine dose every 6 weeks in blinded fashion to achieve different target TSH levels: low-normal TSH (0.34-2.50 mU/L), high-normal TSH (2.51-5.60 mU/L), or mildly elevated TSH (5.60-12.0 mU/L). Patients completed a battery of assessments at baseline and again at 6 months.
Main results confirmed that TSH targets were generally achieved, with significantly different mean TSH levels in the low-normal group (1.34 mU/L), high-normal group (3.74 mU/L), and mildly elevated group (9.74 mU/L) (P less than .05).
In crude analyses, results differed significantly across groups for only two of the dozens of measures of mood, cognition, and QoL assessed: bodily pain (26%, 11%, and 34% of patients reporting a high pain level in the low-normal, high-normal, and mildly elevated TSH groups, respectively; P = .03) and working memory on the N-Back test (86%, 58%, and 75% with a 1-back result; P = .002). However, there were no significant differences for any of the measures when analyses were repeated with statistical correction for multiple comparisons.
At the end of the study, patients were unable to say with any accuracy say whether they were receiving a dose of levothyroxine that was higher than, lower than, or unchanged from their baseline dose (P = .55 for actual vs. perceived).
However, patients preferred what they perceived to be a higher dose (P less than .001 for preferred vs. perceived). In the group perceiving their end-of-study dose was higher, the majority of patients (68%) preferred that dose, and in the group perceiving their end-of-study dose was lower, most (96%) preferred their baseline dose.
The sample size may not have been adequate to detect very small effects of changes in levothyroxine dose, acknowledged Dr. Samuels, who disclosed that she had no relevant conflicts of interest. Additionally, patients were predominantly female and younger, and heterogeneous with respect to thyroid diagnosis and length of levothyroxine therapy.
AT ATA 2017
Key clinical point:
Major finding: Mood, cognition, and QoL were similar across levothyroxine doses targeting various TSH levels, but patients preferred what they believed was a higher dose, even when it was not (P less than .001 for preferred vs. perceived).
Data source: A randomized trial of levothyroxine adjustment among 138 hypothyroid patients on a stable dose of the drug who had normal TSH levels.
Disclosures: Dr. Samuels disclosed that she had no relevant conflicts of interest.
Conjugate typhoid vaccine safe and effective in phase 2 trials
A new conjugate typhoid vaccine suitable for administration to infants and young children was efficacious, highly immunogenic, and well tolerated, compared with placebo, in a phase 2 study that tested the vaccine using a human typhoid infection model.
In a study that compared two formulations of typhoid vaccine to a control meningococcal vaccine, the new Vi-conjugate (Vi-TT) vaccine had an efficacy of 54.6% (95% confidence interval, 26.8-71.8) and a 100% seroconversion rate.
The study was not powered for a direct comparison of the efficacy of the Vi-TT with the efficacy of the Vi-polysaccharide (Vi-PS), the other vaccine used in the study. The Vi-PS vaccine had an efficacy of 52.0% (95% CI, 23.2-70.0), and 88.6% of the Vi-PS recipients had seroconversion.
However, “clinical manifestations of typhoid fever seemed less severe among diagnosed participants following Vi-TT vaccination,” Celina Jin, MD, and her colleagues wrote (Lancet. 2017 Sep 28: doi: 10.1016/S0140-6736[17]32149-9). Fever, defined as an oral temperature of 38° C or higher, was seen in 6 of 37 (16%) Vi-TT recipients, 17 of 31 (55%) receiving control, and 11 of 35 (31%) receiving Vi-PS.
Geometric mean titers also were significantly higher in the Vi-TT group than in the Vi-PS group, with an adjusted geometric mean titer of 562.9 EU/mL for Vi-TT and 140.5 EU/mL for Vi-PS (P less than .0001).
The study enrolled 112 healthy adult volunteers who were randomized 1:1:1 to receive Vi-PS, Vi-TT, or control meningococcal vaccine. A total of 103 of the participants eventually received one of the two study vaccines or the control vaccines, and that group was included in the per-protocol analysis.
After vaccination (recipients and investigators were masked as to which formulation participants received), study participants kept an online diary to report any vaccination-related symptoms for 7 days, and also had clinic visits scheduled at days 1, 3, 7, and 10.
Participants received one oral dose of wild-type Salmonella enterica serovar Typhi Quailes strain bacteria about 1 month after vaccination. The dose was 1-5x104 colony forming units, and was administered immediately following a 120-mL oral bolus of sodium bicarbonate (to neutralize stomach acid).
Participants then were seen daily in an outpatient clinic for 2 weeks. At each visit, investigators monitored vital signs, performed a general assessment, and drew blood to assess for typhoid bacteremia. Participants also kept an online diary for 21 days, reporting twice-daily self-measured temperatures as well. No antipyretics were allowed before typhoid diagnosis.
Participants who met the study’s criteria for typhoid diagnosis were treated with a 2-week course of ciprofloxacin or azithromycin; patients who did not become ill were treated 14 days after the oral typhoid challenge. None of the four serious adverse events reported during the study was deemed to be related to vaccination.
That broad definition of typhoid infection was used to determine attack rates for the study’s primary outcome measure. However, Dr. Jin and her colleagues also looked at a less stringent – and perhaps more clinically pertinent – definition of 12 hours of fever of 38° C or higher followed by S. Typhi bacteremia. Using those criteria, the Vi-TT vaccine prevented up to 87% of infections.
Salmonella Typhi is the world’s leading cause of enteric fever, said Dr. Jin, of the Oxford Vaccine Group at the University of Oxford (England). Up to 20.6 million people per year are affected, with children most commonly infected and low-resource populations in Asia and Africa hardest hit.
Both prescription and over-the-counter antibiotics are used worldwide to combat typhoid fever, and S. Typhi strains are becoming increasingly antibiotic resistant in South Asia and Africa, Dr. Jin and her coauthors said.
The typhoid vaccines that are currently licensed are either not suitable for administration to infants and young children, or are insufficiently immunogenic in younger populations.
The typhoid conjugate vaccine used in the study combines the Vi-polysaccharide capsule with a protein carrier, increasing host immunologic response and making the vaccine effective in infancy.
“This human challenge study provides further evidence to support the deployment of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever, because those individuals living in endemic regions should not be made to wait another 60 years,” wrote Dr. Jin and her coauthors.
The study was funded by the Bill & Melinda Gates Foundation and the European commission FP7 grant, Advanced Immunization Technologies.
The Oxford Vaccine Group has developed a typhoid challenge model that provides an important bridge in clinical testing and affords the possibility of significant acceleration of the vaccine development process. Despite the controversy human challenge models sometimes engender, previous human typhoid challenge studies contributed to the development of the live attenuated typhoid vaccine Ty21a.
The conjugate vaccine tested by Dr. Jin and her colleagues is a much-needed weapon in the public health armamentarium of typhoid control. Treatment options are limited in regions of South Asia and Africa where endemic typhoid shows increasing antibiotic resistance.
This human challenge study provides the first evidence that the conjugate vaccine reduces the attack rate of typhoid fever, though its use in India has shown it to be safe and immunogenic, even in children as young as 6 months of age.
The stringent definition of typhoid fever attack used in this study may result in a finding of lower efficacy than would be seen in a field trial, and a National Institutes of Health–sponsored study of another conjugate vaccine found efficacy rates of 89% among Vietnamese preschoolers followed for nearly 4 years after vaccination. When the present study’s data were reanalyzed with use of the less stringent case definition of fever followed by typhoid bacteremia, a similar efficacy of 87.1% was seen for the conjugate vaccine. A larger sample size would be needed in a challenge study that included the less stringent definition as a coprimary endpoint, but results might better correlate with real-world field trials.
Phase 3 and 4 trials for the typhoid conjugate vaccine are forthcoming, but final results will not be tallied for many years. The typhoid challenge study reported by Dr. Jin and her colleagues bolsters hopes that the candidate vaccine will help with typhoid control where it’s most needed.
Nicholas A. Feasey, MD , is at the Liverpool (England) School of Tropical Medicine. Myron M. Levine, MD , is at the University of Maryland, Baltimore. Their comments were drawn from an editorial accompanying the study (Lancet. 2017 Sep 28. doi: 10.1016/S0140-6736[17]32407-8 ).
The Oxford Vaccine Group has developed a typhoid challenge model that provides an important bridge in clinical testing and affords the possibility of significant acceleration of the vaccine development process. Despite the controversy human challenge models sometimes engender, previous human typhoid challenge studies contributed to the development of the live attenuated typhoid vaccine Ty21a.
The conjugate vaccine tested by Dr. Jin and her colleagues is a much-needed weapon in the public health armamentarium of typhoid control. Treatment options are limited in regions of South Asia and Africa where endemic typhoid shows increasing antibiotic resistance.
This human challenge study provides the first evidence that the conjugate vaccine reduces the attack rate of typhoid fever, though its use in India has shown it to be safe and immunogenic, even in children as young as 6 months of age.
The stringent definition of typhoid fever attack used in this study may result in a finding of lower efficacy than would be seen in a field trial, and a National Institutes of Health–sponsored study of another conjugate vaccine found efficacy rates of 89% among Vietnamese preschoolers followed for nearly 4 years after vaccination. When the present study’s data were reanalyzed with use of the less stringent case definition of fever followed by typhoid bacteremia, a similar efficacy of 87.1% was seen for the conjugate vaccine. A larger sample size would be needed in a challenge study that included the less stringent definition as a coprimary endpoint, but results might better correlate with real-world field trials.
Phase 3 and 4 trials for the typhoid conjugate vaccine are forthcoming, but final results will not be tallied for many years. The typhoid challenge study reported by Dr. Jin and her colleagues bolsters hopes that the candidate vaccine will help with typhoid control where it’s most needed.
Nicholas A. Feasey, MD , is at the Liverpool (England) School of Tropical Medicine. Myron M. Levine, MD , is at the University of Maryland, Baltimore. Their comments were drawn from an editorial accompanying the study (Lancet. 2017 Sep 28. doi: 10.1016/S0140-6736[17]32407-8 ).
The Oxford Vaccine Group has developed a typhoid challenge model that provides an important bridge in clinical testing and affords the possibility of significant acceleration of the vaccine development process. Despite the controversy human challenge models sometimes engender, previous human typhoid challenge studies contributed to the development of the live attenuated typhoid vaccine Ty21a.
The conjugate vaccine tested by Dr. Jin and her colleagues is a much-needed weapon in the public health armamentarium of typhoid control. Treatment options are limited in regions of South Asia and Africa where endemic typhoid shows increasing antibiotic resistance.
This human challenge study provides the first evidence that the conjugate vaccine reduces the attack rate of typhoid fever, though its use in India has shown it to be safe and immunogenic, even in children as young as 6 months of age.
The stringent definition of typhoid fever attack used in this study may result in a finding of lower efficacy than would be seen in a field trial, and a National Institutes of Health–sponsored study of another conjugate vaccine found efficacy rates of 89% among Vietnamese preschoolers followed for nearly 4 years after vaccination. When the present study’s data were reanalyzed with use of the less stringent case definition of fever followed by typhoid bacteremia, a similar efficacy of 87.1% was seen for the conjugate vaccine. A larger sample size would be needed in a challenge study that included the less stringent definition as a coprimary endpoint, but results might better correlate with real-world field trials.
Phase 3 and 4 trials for the typhoid conjugate vaccine are forthcoming, but final results will not be tallied for many years. The typhoid challenge study reported by Dr. Jin and her colleagues bolsters hopes that the candidate vaccine will help with typhoid control where it’s most needed.
Nicholas A. Feasey, MD , is at the Liverpool (England) School of Tropical Medicine. Myron M. Levine, MD , is at the University of Maryland, Baltimore. Their comments were drawn from an editorial accompanying the study (Lancet. 2017 Sep 28. doi: 10.1016/S0140-6736[17]32407-8 ).
A new conjugate typhoid vaccine suitable for administration to infants and young children was efficacious, highly immunogenic, and well tolerated, compared with placebo, in a phase 2 study that tested the vaccine using a human typhoid infection model.
In a study that compared two formulations of typhoid vaccine to a control meningococcal vaccine, the new Vi-conjugate (Vi-TT) vaccine had an efficacy of 54.6% (95% confidence interval, 26.8-71.8) and a 100% seroconversion rate.
The study was not powered for a direct comparison of the efficacy of the Vi-TT with the efficacy of the Vi-polysaccharide (Vi-PS), the other vaccine used in the study. The Vi-PS vaccine had an efficacy of 52.0% (95% CI, 23.2-70.0), and 88.6% of the Vi-PS recipients had seroconversion.
However, “clinical manifestations of typhoid fever seemed less severe among diagnosed participants following Vi-TT vaccination,” Celina Jin, MD, and her colleagues wrote (Lancet. 2017 Sep 28: doi: 10.1016/S0140-6736[17]32149-9). Fever, defined as an oral temperature of 38° C or higher, was seen in 6 of 37 (16%) Vi-TT recipients, 17 of 31 (55%) receiving control, and 11 of 35 (31%) receiving Vi-PS.
Geometric mean titers also were significantly higher in the Vi-TT group than in the Vi-PS group, with an adjusted geometric mean titer of 562.9 EU/mL for Vi-TT and 140.5 EU/mL for Vi-PS (P less than .0001).
The study enrolled 112 healthy adult volunteers who were randomized 1:1:1 to receive Vi-PS, Vi-TT, or control meningococcal vaccine. A total of 103 of the participants eventually received one of the two study vaccines or the control vaccines, and that group was included in the per-protocol analysis.
After vaccination (recipients and investigators were masked as to which formulation participants received), study participants kept an online diary to report any vaccination-related symptoms for 7 days, and also had clinic visits scheduled at days 1, 3, 7, and 10.
Participants received one oral dose of wild-type Salmonella enterica serovar Typhi Quailes strain bacteria about 1 month after vaccination. The dose was 1-5x104 colony forming units, and was administered immediately following a 120-mL oral bolus of sodium bicarbonate (to neutralize stomach acid).
Participants then were seen daily in an outpatient clinic for 2 weeks. At each visit, investigators monitored vital signs, performed a general assessment, and drew blood to assess for typhoid bacteremia. Participants also kept an online diary for 21 days, reporting twice-daily self-measured temperatures as well. No antipyretics were allowed before typhoid diagnosis.
Participants who met the study’s criteria for typhoid diagnosis were treated with a 2-week course of ciprofloxacin or azithromycin; patients who did not become ill were treated 14 days after the oral typhoid challenge. None of the four serious adverse events reported during the study was deemed to be related to vaccination.
That broad definition of typhoid infection was used to determine attack rates for the study’s primary outcome measure. However, Dr. Jin and her colleagues also looked at a less stringent – and perhaps more clinically pertinent – definition of 12 hours of fever of 38° C or higher followed by S. Typhi bacteremia. Using those criteria, the Vi-TT vaccine prevented up to 87% of infections.
Salmonella Typhi is the world’s leading cause of enteric fever, said Dr. Jin, of the Oxford Vaccine Group at the University of Oxford (England). Up to 20.6 million people per year are affected, with children most commonly infected and low-resource populations in Asia and Africa hardest hit.
Both prescription and over-the-counter antibiotics are used worldwide to combat typhoid fever, and S. Typhi strains are becoming increasingly antibiotic resistant in South Asia and Africa, Dr. Jin and her coauthors said.
The typhoid vaccines that are currently licensed are either not suitable for administration to infants and young children, or are insufficiently immunogenic in younger populations.
The typhoid conjugate vaccine used in the study combines the Vi-polysaccharide capsule with a protein carrier, increasing host immunologic response and making the vaccine effective in infancy.
“This human challenge study provides further evidence to support the deployment of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever, because those individuals living in endemic regions should not be made to wait another 60 years,” wrote Dr. Jin and her coauthors.
The study was funded by the Bill & Melinda Gates Foundation and the European commission FP7 grant, Advanced Immunization Technologies.
A new conjugate typhoid vaccine suitable for administration to infants and young children was efficacious, highly immunogenic, and well tolerated, compared with placebo, in a phase 2 study that tested the vaccine using a human typhoid infection model.
In a study that compared two formulations of typhoid vaccine to a control meningococcal vaccine, the new Vi-conjugate (Vi-TT) vaccine had an efficacy of 54.6% (95% confidence interval, 26.8-71.8) and a 100% seroconversion rate.
The study was not powered for a direct comparison of the efficacy of the Vi-TT with the efficacy of the Vi-polysaccharide (Vi-PS), the other vaccine used in the study. The Vi-PS vaccine had an efficacy of 52.0% (95% CI, 23.2-70.0), and 88.6% of the Vi-PS recipients had seroconversion.
However, “clinical manifestations of typhoid fever seemed less severe among diagnosed participants following Vi-TT vaccination,” Celina Jin, MD, and her colleagues wrote (Lancet. 2017 Sep 28: doi: 10.1016/S0140-6736[17]32149-9). Fever, defined as an oral temperature of 38° C or higher, was seen in 6 of 37 (16%) Vi-TT recipients, 17 of 31 (55%) receiving control, and 11 of 35 (31%) receiving Vi-PS.
Geometric mean titers also were significantly higher in the Vi-TT group than in the Vi-PS group, with an adjusted geometric mean titer of 562.9 EU/mL for Vi-TT and 140.5 EU/mL for Vi-PS (P less than .0001).
The study enrolled 112 healthy adult volunteers who were randomized 1:1:1 to receive Vi-PS, Vi-TT, or control meningococcal vaccine. A total of 103 of the participants eventually received one of the two study vaccines or the control vaccines, and that group was included in the per-protocol analysis.
After vaccination (recipients and investigators were masked as to which formulation participants received), study participants kept an online diary to report any vaccination-related symptoms for 7 days, and also had clinic visits scheduled at days 1, 3, 7, and 10.
Participants received one oral dose of wild-type Salmonella enterica serovar Typhi Quailes strain bacteria about 1 month after vaccination. The dose was 1-5x104 colony forming units, and was administered immediately following a 120-mL oral bolus of sodium bicarbonate (to neutralize stomach acid).
Participants then were seen daily in an outpatient clinic for 2 weeks. At each visit, investigators monitored vital signs, performed a general assessment, and drew blood to assess for typhoid bacteremia. Participants also kept an online diary for 21 days, reporting twice-daily self-measured temperatures as well. No antipyretics were allowed before typhoid diagnosis.
Participants who met the study’s criteria for typhoid diagnosis were treated with a 2-week course of ciprofloxacin or azithromycin; patients who did not become ill were treated 14 days after the oral typhoid challenge. None of the four serious adverse events reported during the study was deemed to be related to vaccination.
That broad definition of typhoid infection was used to determine attack rates for the study’s primary outcome measure. However, Dr. Jin and her colleagues also looked at a less stringent – and perhaps more clinically pertinent – definition of 12 hours of fever of 38° C or higher followed by S. Typhi bacteremia. Using those criteria, the Vi-TT vaccine prevented up to 87% of infections.
Salmonella Typhi is the world’s leading cause of enteric fever, said Dr. Jin, of the Oxford Vaccine Group at the University of Oxford (England). Up to 20.6 million people per year are affected, with children most commonly infected and low-resource populations in Asia and Africa hardest hit.
Both prescription and over-the-counter antibiotics are used worldwide to combat typhoid fever, and S. Typhi strains are becoming increasingly antibiotic resistant in South Asia and Africa, Dr. Jin and her coauthors said.
The typhoid vaccines that are currently licensed are either not suitable for administration to infants and young children, or are insufficiently immunogenic in younger populations.
The typhoid conjugate vaccine used in the study combines the Vi-polysaccharide capsule with a protein carrier, increasing host immunologic response and making the vaccine effective in infancy.
“This human challenge study provides further evidence to support the deployment of Vi-conjugate vaccines as a control measure to reduce the burden of typhoid fever, because those individuals living in endemic regions should not be made to wait another 60 years,” wrote Dr. Jin and her coauthors.
The study was funded by the Bill & Melinda Gates Foundation and the European commission FP7 grant, Advanced Immunization Technologies.
FROM THE LANCET
Key clinical point: A conjugate typhoid vaccine significantly reduced typhoid fever rates under a stringent case definition.
Major finding: Efficacy was 54.6% for the Vi-conjugate vaccine, with 100% seroconversion.
Study details: Randomized, controlled phase 2b trial of 112 participants receiving one of two typhoid vaccines, or control meningococcal vaccine.
Disclosures: The study was funded by the Bill & Melinda Gates Foundation and the European Commission FP7 grant, Advanced Immunization Technologies.
CHEST Physician’s planned coverage of CHEST 2017
CHEST Physician is providing on-site coverage of the CHEST annual meeting in Toronto from Oct. 29 through Nov. 1.
We are planning to share findings from the latest research on treating COPD, sleep apnea, pulmonary hypertension, severe asthma, and other diseases that are part of pulmonary, critical care, and sleep medicine. Any improved methods for managing an ICU and updated recommendations on screening for lung cancer will also be on our radar.
The meeting’s agenda includes presentations of hundreds of study abstracts, and we thought you would be interested in hearing which ones grabbed the attention of some of CHEST Physician’s editorial advisory board members.
Board member Susan L. Millard, MD, FCCP, suggested attendees check out presentations of the following two studies:
- Impact of Race on Quality of Life of Families of Children with Asthma when Asthma Guidelines are Followed: Long-Term Follow-Up
- Results Of A Phase 3, Multicenter, Randomized, Placebo-controlled Trial of Remimazolam: A New Ultra Short Acting Benzodiazepine for Bronchoscopy
The first study is part of a session entitled Pediatrics, scheduled to run from 3:15 to 4:15 p.m. on Sunday, Oct. 29, in Convention Center - 606. Shahid Sheikh, MD, of Nationwide Children’s Hospital in New Albany, Ohio, is scheduled to present the abstract at 4:00 p.m.
Dr. Millard, who is Therapeutic Development Network director for the Pediatric CF Care Center and director of research for pediatric pulmonary and sleep medicine at the Helen DeVos Children’s Hospital in Grand Rapids, Mich., noted that she is interested in Dr. Sheikh’s research, “because cultural diversity is such a hot topic in general.”
Her other recommendation is part of the Late Breaking Abstracts 2 session, scheduled to occur on Wednesday, Nov. 1, from 2:45 to 4:15 p.m. in Convention Center - 603. CHEST President, Gerard A. Silvestri, MD, MS, FCCP, will present the abstract at 4:00 p.m.
Dr. Millard said she is interested in this study, because new drug options are so helpful for the frequently performed bronchoscopy.
Two sleep medicine experts on CHEST Physician’s editorial advisory board also selected a few presentations they expect to be newsworthy.
David Schulman, MD, MPH, FCCP, and professor of medicine at Emory University School of Medicine in Atlanta suggested CHEST Physician cover the following studies:
- Results of a Randomized, Placebo-Controlled, Double-Blind, 12-Week, Multicenter Study of JZP-110 for the Treatment Of Excessive Sleepiness in Patients with OSA, scheduled to be presented on Sunday, Oct. 29, at 1:30 p.m. in Convention Center - 601A. Dr. Kingman Strohl, MD, FCCP, of University Hospitals Case Medical Center-Sleep Center in Shaker Heights, Ohio, will present this research during a session entitled, Obstructive Sleep Apnea: Insights & Management, running from 1:30 to 3:00 p.m.
- History of Sleep Apnea and Cardiovascular Disease may Portend Improved Mortality in Patients With Acute Ischemic Stroke, scheduled to be presented on Tuesday, Oct. 31, at 11:15 a.m., in Convention Center - 601A. Nura Festic will present this research during the session, “Sleep, Heart, Brain and More,” running from 11:00 a.m. to 12:15 p.m.
- Ischemic Preconditioning in OSA Patients Manifested after Surviving a Cardiac Arrest? John Moss, MD, of Jacksonville, Fla., will present this study on Tuesday, Oct. 31, at 11:30 a.m., in Convention Center - 601A as part of the session “Sleep, Heart, Brain and More.”
Krishna M. Sundar, MD, FCCP, also recommended that CHEST Physician cover “A Prospective Cohort Study of Endothelial Function and its Relationship to Aspirin Responsiveness in OSA Patients.” Lirim Krveshi is scheduled to present this study on Sunday, Oct. 29, at 1:45 p.m. in Convention Center - 601A. This presentation is part of the Obstructive Sleep Apnea: Insights & Management session.
Dr. Sundar is an associate clinical professor of pulmonary, critical care and sleep medicine and medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City.
To view the full agenda of the CHEST annual meeting, visit: chestmeeting.chestnet.org.
Look for CHEST Physician’s coverage of CHEST 2017 on our conference coverage page.
CHEST Physician is providing on-site coverage of the CHEST annual meeting in Toronto from Oct. 29 through Nov. 1.
We are planning to share findings from the latest research on treating COPD, sleep apnea, pulmonary hypertension, severe asthma, and other diseases that are part of pulmonary, critical care, and sleep medicine. Any improved methods for managing an ICU and updated recommendations on screening for lung cancer will also be on our radar.
The meeting’s agenda includes presentations of hundreds of study abstracts, and we thought you would be interested in hearing which ones grabbed the attention of some of CHEST Physician’s editorial advisory board members.
Board member Susan L. Millard, MD, FCCP, suggested attendees check out presentations of the following two studies:
- Impact of Race on Quality of Life of Families of Children with Asthma when Asthma Guidelines are Followed: Long-Term Follow-Up
- Results Of A Phase 3, Multicenter, Randomized, Placebo-controlled Trial of Remimazolam: A New Ultra Short Acting Benzodiazepine for Bronchoscopy
The first study is part of a session entitled Pediatrics, scheduled to run from 3:15 to 4:15 p.m. on Sunday, Oct. 29, in Convention Center - 606. Shahid Sheikh, MD, of Nationwide Children’s Hospital in New Albany, Ohio, is scheduled to present the abstract at 4:00 p.m.
Dr. Millard, who is Therapeutic Development Network director for the Pediatric CF Care Center and director of research for pediatric pulmonary and sleep medicine at the Helen DeVos Children’s Hospital in Grand Rapids, Mich., noted that she is interested in Dr. Sheikh’s research, “because cultural diversity is such a hot topic in general.”
Her other recommendation is part of the Late Breaking Abstracts 2 session, scheduled to occur on Wednesday, Nov. 1, from 2:45 to 4:15 p.m. in Convention Center - 603. CHEST President, Gerard A. Silvestri, MD, MS, FCCP, will present the abstract at 4:00 p.m.
Dr. Millard said she is interested in this study, because new drug options are so helpful for the frequently performed bronchoscopy.
Two sleep medicine experts on CHEST Physician’s editorial advisory board also selected a few presentations they expect to be newsworthy.
David Schulman, MD, MPH, FCCP, and professor of medicine at Emory University School of Medicine in Atlanta suggested CHEST Physician cover the following studies:
- Results of a Randomized, Placebo-Controlled, Double-Blind, 12-Week, Multicenter Study of JZP-110 for the Treatment Of Excessive Sleepiness in Patients with OSA, scheduled to be presented on Sunday, Oct. 29, at 1:30 p.m. in Convention Center - 601A. Dr. Kingman Strohl, MD, FCCP, of University Hospitals Case Medical Center-Sleep Center in Shaker Heights, Ohio, will present this research during a session entitled, Obstructive Sleep Apnea: Insights & Management, running from 1:30 to 3:00 p.m.
- History of Sleep Apnea and Cardiovascular Disease may Portend Improved Mortality in Patients With Acute Ischemic Stroke, scheduled to be presented on Tuesday, Oct. 31, at 11:15 a.m., in Convention Center - 601A. Nura Festic will present this research during the session, “Sleep, Heart, Brain and More,” running from 11:00 a.m. to 12:15 p.m.
- Ischemic Preconditioning in OSA Patients Manifested after Surviving a Cardiac Arrest? John Moss, MD, of Jacksonville, Fla., will present this study on Tuesday, Oct. 31, at 11:30 a.m., in Convention Center - 601A as part of the session “Sleep, Heart, Brain and More.”
Krishna M. Sundar, MD, FCCP, also recommended that CHEST Physician cover “A Prospective Cohort Study of Endothelial Function and its Relationship to Aspirin Responsiveness in OSA Patients.” Lirim Krveshi is scheduled to present this study on Sunday, Oct. 29, at 1:45 p.m. in Convention Center - 601A. This presentation is part of the Obstructive Sleep Apnea: Insights & Management session.
Dr. Sundar is an associate clinical professor of pulmonary, critical care and sleep medicine and medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City.
To view the full agenda of the CHEST annual meeting, visit: chestmeeting.chestnet.org.
Look for CHEST Physician’s coverage of CHEST 2017 on our conference coverage page.
CHEST Physician is providing on-site coverage of the CHEST annual meeting in Toronto from Oct. 29 through Nov. 1.
We are planning to share findings from the latest research on treating COPD, sleep apnea, pulmonary hypertension, severe asthma, and other diseases that are part of pulmonary, critical care, and sleep medicine. Any improved methods for managing an ICU and updated recommendations on screening for lung cancer will also be on our radar.
The meeting’s agenda includes presentations of hundreds of study abstracts, and we thought you would be interested in hearing which ones grabbed the attention of some of CHEST Physician’s editorial advisory board members.
Board member Susan L. Millard, MD, FCCP, suggested attendees check out presentations of the following two studies:
- Impact of Race on Quality of Life of Families of Children with Asthma when Asthma Guidelines are Followed: Long-Term Follow-Up
- Results Of A Phase 3, Multicenter, Randomized, Placebo-controlled Trial of Remimazolam: A New Ultra Short Acting Benzodiazepine for Bronchoscopy
The first study is part of a session entitled Pediatrics, scheduled to run from 3:15 to 4:15 p.m. on Sunday, Oct. 29, in Convention Center - 606. Shahid Sheikh, MD, of Nationwide Children’s Hospital in New Albany, Ohio, is scheduled to present the abstract at 4:00 p.m.
Dr. Millard, who is Therapeutic Development Network director for the Pediatric CF Care Center and director of research for pediatric pulmonary and sleep medicine at the Helen DeVos Children’s Hospital in Grand Rapids, Mich., noted that she is interested in Dr. Sheikh’s research, “because cultural diversity is such a hot topic in general.”
Her other recommendation is part of the Late Breaking Abstracts 2 session, scheduled to occur on Wednesday, Nov. 1, from 2:45 to 4:15 p.m. in Convention Center - 603. CHEST President, Gerard A. Silvestri, MD, MS, FCCP, will present the abstract at 4:00 p.m.
Dr. Millard said she is interested in this study, because new drug options are so helpful for the frequently performed bronchoscopy.
Two sleep medicine experts on CHEST Physician’s editorial advisory board also selected a few presentations they expect to be newsworthy.
David Schulman, MD, MPH, FCCP, and professor of medicine at Emory University School of Medicine in Atlanta suggested CHEST Physician cover the following studies:
- Results of a Randomized, Placebo-Controlled, Double-Blind, 12-Week, Multicenter Study of JZP-110 for the Treatment Of Excessive Sleepiness in Patients with OSA, scheduled to be presented on Sunday, Oct. 29, at 1:30 p.m. in Convention Center - 601A. Dr. Kingman Strohl, MD, FCCP, of University Hospitals Case Medical Center-Sleep Center in Shaker Heights, Ohio, will present this research during a session entitled, Obstructive Sleep Apnea: Insights & Management, running from 1:30 to 3:00 p.m.
- History of Sleep Apnea and Cardiovascular Disease may Portend Improved Mortality in Patients With Acute Ischemic Stroke, scheduled to be presented on Tuesday, Oct. 31, at 11:15 a.m., in Convention Center - 601A. Nura Festic will present this research during the session, “Sleep, Heart, Brain and More,” running from 11:00 a.m. to 12:15 p.m.
- Ischemic Preconditioning in OSA Patients Manifested after Surviving a Cardiac Arrest? John Moss, MD, of Jacksonville, Fla., will present this study on Tuesday, Oct. 31, at 11:30 a.m., in Convention Center - 601A as part of the session “Sleep, Heart, Brain and More.”
Krishna M. Sundar, MD, FCCP, also recommended that CHEST Physician cover “A Prospective Cohort Study of Endothelial Function and its Relationship to Aspirin Responsiveness in OSA Patients.” Lirim Krveshi is scheduled to present this study on Sunday, Oct. 29, at 1:45 p.m. in Convention Center - 601A. This presentation is part of the Obstructive Sleep Apnea: Insights & Management session.
Dr. Sundar is an associate clinical professor of pulmonary, critical care and sleep medicine and medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City.
To view the full agenda of the CHEST annual meeting, visit: chestmeeting.chestnet.org.
Look for CHEST Physician’s coverage of CHEST 2017 on our conference coverage page.
FROM CHEST 2017
Stopping anti-TNF drugs in PsA has high rebound risk
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point:
Major finding: Among 94 patients, 69 (73%) experienced symptom rebound after discontinuing their TNFi therapy.
Data source: The prospective observational Corrona disease registry database of about 6,000 patients with PsA.
Disclosures: The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and RA. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
Translating Research Into Practice the NIOSH Way
The National Occupational Research Agenda (NORA), a partnership program created by the National Institute for Occupational Safety and Health (NIOSH), is celebrating its second anniversary with a report addressing the question: how can research be better moved into practice in the workplace?
NORA has focused on 10 industry sectors representing major areas of the U.S. economy, and developed sector councils—comprising of stakeholders from universities, business, professional societies, government agencies, and worker organizations—that set priority research goals for the nation.
In the past 20 years, NIOSH has had an average of 740 active projects per year. It invested an average of $243.8 million per year in research between 2007 - 2015. Between 2007 - 2014, nearly 11,000 publications were developed through NIOSH-funded research.
Outcome measures include whether those NORA outputs have been used by others, in citations and research. NIOSH says its outputs are widely disseminated; the VA and other veterans’ organizations, for instance, disseminated NIOSH information on return-to-work issues for veterans with PTSD. As another example, academicians and researchers are using NIOSH findings to improve tuberculosis risk and prevention education in workplaces. And approximately 50% of the NIOSH products cited by another federal agency in a Federal Register document were aged ≥ 11 years —suggesting that NIOSH documents have a “sustained relevance and impact well beyond their publication date,” the report says.
NIOSH highlights NORA’s progress with “impact stories” about the influence of NORA on health, safety, and wellbeing of the U.S. workforce. Case in point: “Preventing Occupational Transmission of Blood-borne Pathogens Among Healthcare Workers” helped improve worker safety by instructing > 20,000 trainers and leading to new regulations, NIOSH says.
For its third decade, NIOSH says, NORA will build on the “many successes and lessons learned from the first 2 decades of this unique partnership approach.”
The National Occupational Research Agenda (NORA), a partnership program created by the National Institute for Occupational Safety and Health (NIOSH), is celebrating its second anniversary with a report addressing the question: how can research be better moved into practice in the workplace?
NORA has focused on 10 industry sectors representing major areas of the U.S. economy, and developed sector councils—comprising of stakeholders from universities, business, professional societies, government agencies, and worker organizations—that set priority research goals for the nation.
In the past 20 years, NIOSH has had an average of 740 active projects per year. It invested an average of $243.8 million per year in research between 2007 - 2015. Between 2007 - 2014, nearly 11,000 publications were developed through NIOSH-funded research.
Outcome measures include whether those NORA outputs have been used by others, in citations and research. NIOSH says its outputs are widely disseminated; the VA and other veterans’ organizations, for instance, disseminated NIOSH information on return-to-work issues for veterans with PTSD. As another example, academicians and researchers are using NIOSH findings to improve tuberculosis risk and prevention education in workplaces. And approximately 50% of the NIOSH products cited by another federal agency in a Federal Register document were aged ≥ 11 years —suggesting that NIOSH documents have a “sustained relevance and impact well beyond their publication date,” the report says.
NIOSH highlights NORA’s progress with “impact stories” about the influence of NORA on health, safety, and wellbeing of the U.S. workforce. Case in point: “Preventing Occupational Transmission of Blood-borne Pathogens Among Healthcare Workers” helped improve worker safety by instructing > 20,000 trainers and leading to new regulations, NIOSH says.
For its third decade, NIOSH says, NORA will build on the “many successes and lessons learned from the first 2 decades of this unique partnership approach.”
The National Occupational Research Agenda (NORA), a partnership program created by the National Institute for Occupational Safety and Health (NIOSH), is celebrating its second anniversary with a report addressing the question: how can research be better moved into practice in the workplace?
NORA has focused on 10 industry sectors representing major areas of the U.S. economy, and developed sector councils—comprising of stakeholders from universities, business, professional societies, government agencies, and worker organizations—that set priority research goals for the nation.
In the past 20 years, NIOSH has had an average of 740 active projects per year. It invested an average of $243.8 million per year in research between 2007 - 2015. Between 2007 - 2014, nearly 11,000 publications were developed through NIOSH-funded research.
Outcome measures include whether those NORA outputs have been used by others, in citations and research. NIOSH says its outputs are widely disseminated; the VA and other veterans’ organizations, for instance, disseminated NIOSH information on return-to-work issues for veterans with PTSD. As another example, academicians and researchers are using NIOSH findings to improve tuberculosis risk and prevention education in workplaces. And approximately 50% of the NIOSH products cited by another federal agency in a Federal Register document were aged ≥ 11 years —suggesting that NIOSH documents have a “sustained relevance and impact well beyond their publication date,” the report says.
NIOSH highlights NORA’s progress with “impact stories” about the influence of NORA on health, safety, and wellbeing of the U.S. workforce. Case in point: “Preventing Occupational Transmission of Blood-borne Pathogens Among Healthcare Workers” helped improve worker safety by instructing > 20,000 trainers and leading to new regulations, NIOSH says.
For its third decade, NIOSH says, NORA will build on the “many successes and lessons learned from the first 2 decades of this unique partnership approach.”
ATLG fights GVHD but reduces PFS, OS
Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.
In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.
However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.
On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.
These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.
The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.
Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.
In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).
Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.
Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:
- Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.
Overall results
Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).
However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).
In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).
In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).
Role of conditioning, ALC
The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.
For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).
For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).
For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).
The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 109/L, compared to less than 35% of patients who received busulfan-based conditioning.
ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 109/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.
ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1. 
Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.
In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.
However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.
On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.
These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.
The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.
Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.
In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).
Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.
Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:
- Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.
Overall results
Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).
However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).
In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).
In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).
Role of conditioning, ALC
The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.
For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).
For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).
For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).
The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 109/L, compared to less than 35% of patients who received busulfan-based conditioning.
ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 109/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.
ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1.
Results of a phase 3 trial suggest rabbit anti-T lymphocyte globulin (ATLG) can reduce graft-versus-host disease (GVHD) but also decrease survival in patients who have received a hematopoietic stem cell transplant (HSCT) from a matched, unrelated donor.
In this randomized trial, ATLG significantly decreased the incidence of moderate-to-severe chronic GVHD and acute grade 2-4 GVHD, when compared to placebo.
However, patients who received ATLG also had significantly lower progression-free survival (PFS) and overall survival (OS) than placebo-treated patients.
On the other hand, the data also suggest that patients who receive conditioning regimens that do not lower absolute lymphocyte counts (ALCs) substantially may not experience a significant decrease in survival with ATLG.
These results were published in the Journal of Clinical Oncology. The study was sponsored by Neovii Pharmaceuticals AG, which is developing ATLG as Grafalon®.
The study was a prospective, randomized, double-blind trial conducted in North America and Australia (NCT01295710). It enrolled 254 patients, ages 18 to 65, who had acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndromes. All patients were undergoing myeloablative, HLA-matched, unrelated HSCT.
Patients were randomized in a 1:1 fashion to receive ATLG (given at 20 mg/kg/day, n=126) or placebo (250 ml of normal saline, n=128) on days -3, -2, and -1 prior to HSCT.
In addition, all patients received antihistamine and methylprednisolone (at 2 mg/kg on day -3 and 1 mg/kg on days -2 and -1).
Patients also received GVHD prophylaxis in the form of tacrolimus (with a target serum trough level of 5 to 15 ng/mL) and methotrexate (15 mg/m2 on day 1, then 10 mg/m2 on days 3, 6, and 11). If patients did not develop clinical GVHD, tacrolimus was tapered starting on day 50 or later over a minimum of 26 weeks and ultimately discontinued.
Patients received 1 of 3 conditioning regimens, which were declared prior to randomization and included:
- Cyclophosphamide at 120 mg/kg intravenously (IV) and fractionated total body irradiation (TBI, ≥12 Gy)
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and cyclophosphamide at 120 mg/kg IV
- Busulfan at 16 mg/kg orally or 12.8 mg/kg IV and fludarabine at 120 mg/m2 IV.
Overall results
Compared to placebo-treated patients, those who received ATLG had a significant reduction in grade 2-4 acute GVHD—23% and 40%, respectively (P=0.004)—and moderate-to-severe chronic GVHD—12% and 33%, respectively (P<0.001).
However, there was no significant difference between the ATLG and placebo arms with regard to moderate-severe chronic GVHD-free survival. The 2-year estimate was 48% and 44%, respectively (P=0.47).
In addition, PFS and OS were significantly lower in patients who received ATLG. The estimated 2-year PFS was 47% in the ATLG arm and 65% in the placebo arm (P=0.04). The estimated 2-year OS was 59% and 74%, respectively (P=0.034).
In a multivariable analysis, ATLG remained significantly associated with inferior PFS (hazard ratio [HR]=1.55, P=0.026) and OS (hazard ratio=1.74, P=0.01).
Role of conditioning, ALC
The researchers found evidence to suggest that conditioning regimen and ALC played a role in patient outcomes.
For patients who received cyclophosphamide and TBI, 2-year moderate-severe chronic GVHD-free survival was 61% in the placebo arm and 38% in the ATLG arm (P=0.080). Two-year OS was 88% and 48%, respectively (P=0.006). And 2-year PFS was 75% and 29%, respectively (P=0.007).
For patients who received busulfan and cyclophosphamide, 2-year moderate-severe chronic GVHD-free survival was 47% in the placebo arm and 53% in the ATLG arm (P=0.650). Two-year OS was 77% and 71%, respectively (P=0.350). And 2-year PFS was 73% and 60%, respectively (P=0.460).
For patients who received busulfan and fludarabine, 2-year moderate-severe chronic GVHD-free survival was 33% in the placebo arm and 49% in the ATLG arm (P=0.047). Two-year OS was 66% and 53%, respectively (P=0.520). And 2-year PFS was 58% and 48%, respectively (P=0.540).
The researchers noted that the choice of conditioning regimen had a “profound effect” on ALC at day -3 (the time of ATLG/placebo initiation). More than 70% of patients who received TBI had an ALC <0.1 x 109/L, compared to less than 35% of patients who received busulfan-based conditioning.
ALC, in turn, had an impact on PFS and OS. In patients with an ALC ≥ 0.1 x 109/L on day -3, ATLG did not compromise PFS or OS, but PFS and OS were negatively affected in patients with an ALC < 0.1.
ATLG recipients with an ALC < 0.1 had significantly worse OS (HR=4.13, P<0.001) and PFS (HR=3.19, P<0.001) than patients with an ALC ≥ 0.1.
Gene therapy granted orphan designation for hemophilia A
The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.
SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.
Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.
In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.
The FDA also granted orphan designation to SHP654. The agency grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.
“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”
The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.
SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.
Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.
In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.
The FDA also granted orphan designation to SHP654. The agency grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.
“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”
The US Food and Drug Administration (FDA) has accepted an investigational new drug application for SHP654 (also known as BAX 888) and granted the therapy orphan drug designation.
SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using an adeno-associated virus serotype 8 vector to deliver codon-optimized, B-domain-deleted FVIII specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.
Shire, the company developing SHP654, received FDA clearance for an investigational new drug application to initiate a global, phase 1/2 study of SHP654.
In this study, researchers will evaluate the safety and optimal dose of SHP654 needed to boost FVIII activity levels and affect hemophilic bleeding. Shire expects this study will begin by the end of this year.
The FDA also granted orphan designation to SHP654. The agency grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
“This important orphan drug designation highlights Shire’s commitment to patients with rare diseases, and, for hemophilia patients specifically, our aim is to help them achieve zero bleeds,” said Paul Monahan, MD, senior medical director of gene therapy at Shire.
“We know that hemophilia care is not one-size-fits-all and that every patient is unique, which is why we continue to focus on optimizing personal outcomes for hemophilia patients by developing innovations to transform care.”
Automated blood analyzers approved in China
The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.
The platform consists of ORTHO VISION and ORTHO VISION Max.
ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.
According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.
The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.
The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.
The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.
ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.
“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.
“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.”
The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.
The platform consists of ORTHO VISION and ORTHO VISION Max.
ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.
According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.
The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.
The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.
The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.
ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.
“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.
“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.”
The China Food and Drug Administration has approved Ortho Clinical Diagnostics’ ORTHO VISION® Platform of fully automated blood analyzers for transfusion medicine laboratories.
The platform consists of ORTHO VISION and ORTHO VISION Max.
ORTHO VISION is a blood analyzer designed for small- to mid-sized transfusion labs, and ORTHO VISION Max is an analyzer developed for mid- to high-volume labs.
According to Ortho Clinical Diagnostics, the ORTHO VISION Platform automates more tests than ever before and takes less time to perform those tests.
The platform supports complex immunohematology testing such as serial dilutions for titration studies, reflex tests, and selected cell antibody identification.
The ORTHO VISION Platform also has scheduling intelligence, which allows a transfusion medicine department to process routine samples and STAT orders as they are received, rather than waiting for a complete batch before running the instrument.
The ORTHO VISION Platform offers dynamic workflow and lab standardization across instrumentation, technology, procedures, and training. These features are intended to help labs keep pace with growing industry pressure to increase productivity while remaining operationally efficient.
ORTHO VISION and ORTHO VISION Max are commercially available in countries other than China as well, including the US, Japan, and European countries.
“Around the world, transfusion medicine labs are facing increasing pressure to perform more tests with fewer resources, and yet their work in ensuring that all patients receive safe and appropriate blood remains critically important,” said Robert Yates, chief operating officer of Ortho Clinical Diagnostics.
“Ortho is committed to helping labs become more efficient while continuing to perform precise, accurate testing.”