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Senate parliamentarian upends GOP hopes for health bill
The official rules keeper in the Senate tossed a bucket of cold water July 21 on the Senate Republican health bill by advising that major parts of the bill cannot be passed with a simple majority, but rather would require 60 votes. Republicans hold only 52 seats in the Senate.
Senate Parliamentarian Elizabeth MacDonough said that a super-majority is needed for the temporary defunding of Planned Parenthood, abortion coverage restrictions to health plans purchased with tax credits, and the requirement that people with breaks in coverage wait 6 months before they can purchase new plans.
The list was released by Democrats on the Senate Budget Committee and later confirmed by a spokesman for the committee Republicans. It is the result of what is called the “Byrd Bath,” a process in which the parliamentarian hears arguments from Democrats and Republicans and then advises on which provisions comply with the Byrd Rule. That rule requires that only matters directly pertaining to the federal budget are included. The rule is named for former Senate Majority Leader Robert Byrd (D-W.Va.), who first wrote it.
Senate Republicans were quick to point out that the document is “guidance” that they can use to try to rewrite impermissible language. The guidance “will help inform action on the legislation going forward,” said a spokesman for Senate Budget Committee Chairman Mike Enzi (R-Wyo.).
Among the other provisions that the parliamentarian has advised should require 60 votes are ones that would eliminate Medicaid requirements to provide 10 “essential health benefits.” Also on the list is a provision to repeal a requirement that insurers spend a minimum amount of each premium dollar on direct medical services, rather than administration or profits.
The determination also pertains to a part of the bill that would continue payments for “cost-sharing subsidies” to insurers for 2 more years. Those subsidies help lower-income people afford out-of-pocket costs such as deductibles. The parliamentarian said that duplicated existing law.
Ms. MacDonough also said that a provision in the House version of the bill that pertains directly to New York violates the Byrd Rule. That measure would change the way the state collects money for Medicaid. That could suggest efforts by Senate Majority Leader Mitch McConnell (R-Ky.) to offer state-specific changes to gain support for the bill might meet the same fate.
Minority Leader Chuck Schumer (D-N.Y.) said that decision could have “the greatest effect on Republicans’ ability to pass this bill.” He predicted it would “tie the majority leader’s hands as he tries to win over reluctant Republicans.”
Some of the provisions that didn’t pass muster with Ms. MacDonough were key to getting the bill through the House. And if they are dropped, it might make it difficult for the House to approve a final version of the bill.
Not all the decisions went the Democrats’ way. Ms. MacDonough found that only a simple majority is needed for language allowing states to impose work requirements for Medicaid recipients. She also said that a provision that will ban abortions if the services are paid through a new fund provided to states would be allowed. That’s because that fund will be governed by existing rules that already ban abortion in most cases.
A few provisions remain under review, according to the list. Those include allowing states to waive a long list of insurance protections, including the ACA’s essential health benefits and preexisting coverage guarantees. Also still under review is language allowing small businesses to pool together to purchase insurance as well as a provision changing requirements related to how much more insurers can charge older adults.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
The official rules keeper in the Senate tossed a bucket of cold water July 21 on the Senate Republican health bill by advising that major parts of the bill cannot be passed with a simple majority, but rather would require 60 votes. Republicans hold only 52 seats in the Senate.
Senate Parliamentarian Elizabeth MacDonough said that a super-majority is needed for the temporary defunding of Planned Parenthood, abortion coverage restrictions to health plans purchased with tax credits, and the requirement that people with breaks in coverage wait 6 months before they can purchase new plans.
The list was released by Democrats on the Senate Budget Committee and later confirmed by a spokesman for the committee Republicans. It is the result of what is called the “Byrd Bath,” a process in which the parliamentarian hears arguments from Democrats and Republicans and then advises on which provisions comply with the Byrd Rule. That rule requires that only matters directly pertaining to the federal budget are included. The rule is named for former Senate Majority Leader Robert Byrd (D-W.Va.), who first wrote it.
Senate Republicans were quick to point out that the document is “guidance” that they can use to try to rewrite impermissible language. The guidance “will help inform action on the legislation going forward,” said a spokesman for Senate Budget Committee Chairman Mike Enzi (R-Wyo.).
Among the other provisions that the parliamentarian has advised should require 60 votes are ones that would eliminate Medicaid requirements to provide 10 “essential health benefits.” Also on the list is a provision to repeal a requirement that insurers spend a minimum amount of each premium dollar on direct medical services, rather than administration or profits.
The determination also pertains to a part of the bill that would continue payments for “cost-sharing subsidies” to insurers for 2 more years. Those subsidies help lower-income people afford out-of-pocket costs such as deductibles. The parliamentarian said that duplicated existing law.
Ms. MacDonough also said that a provision in the House version of the bill that pertains directly to New York violates the Byrd Rule. That measure would change the way the state collects money for Medicaid. That could suggest efforts by Senate Majority Leader Mitch McConnell (R-Ky.) to offer state-specific changes to gain support for the bill might meet the same fate.
Minority Leader Chuck Schumer (D-N.Y.) said that decision could have “the greatest effect on Republicans’ ability to pass this bill.” He predicted it would “tie the majority leader’s hands as he tries to win over reluctant Republicans.”
Some of the provisions that didn’t pass muster with Ms. MacDonough were key to getting the bill through the House. And if they are dropped, it might make it difficult for the House to approve a final version of the bill.
Not all the decisions went the Democrats’ way. Ms. MacDonough found that only a simple majority is needed for language allowing states to impose work requirements for Medicaid recipients. She also said that a provision that will ban abortions if the services are paid through a new fund provided to states would be allowed. That’s because that fund will be governed by existing rules that already ban abortion in most cases.
A few provisions remain under review, according to the list. Those include allowing states to waive a long list of insurance protections, including the ACA’s essential health benefits and preexisting coverage guarantees. Also still under review is language allowing small businesses to pool together to purchase insurance as well as a provision changing requirements related to how much more insurers can charge older adults.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
The official rules keeper in the Senate tossed a bucket of cold water July 21 on the Senate Republican health bill by advising that major parts of the bill cannot be passed with a simple majority, but rather would require 60 votes. Republicans hold only 52 seats in the Senate.
Senate Parliamentarian Elizabeth MacDonough said that a super-majority is needed for the temporary defunding of Planned Parenthood, abortion coverage restrictions to health plans purchased with tax credits, and the requirement that people with breaks in coverage wait 6 months before they can purchase new plans.
The list was released by Democrats on the Senate Budget Committee and later confirmed by a spokesman for the committee Republicans. It is the result of what is called the “Byrd Bath,” a process in which the parliamentarian hears arguments from Democrats and Republicans and then advises on which provisions comply with the Byrd Rule. That rule requires that only matters directly pertaining to the federal budget are included. The rule is named for former Senate Majority Leader Robert Byrd (D-W.Va.), who first wrote it.
Senate Republicans were quick to point out that the document is “guidance” that they can use to try to rewrite impermissible language. The guidance “will help inform action on the legislation going forward,” said a spokesman for Senate Budget Committee Chairman Mike Enzi (R-Wyo.).
Among the other provisions that the parliamentarian has advised should require 60 votes are ones that would eliminate Medicaid requirements to provide 10 “essential health benefits.” Also on the list is a provision to repeal a requirement that insurers spend a minimum amount of each premium dollar on direct medical services, rather than administration or profits.
The determination also pertains to a part of the bill that would continue payments for “cost-sharing subsidies” to insurers for 2 more years. Those subsidies help lower-income people afford out-of-pocket costs such as deductibles. The parliamentarian said that duplicated existing law.
Ms. MacDonough also said that a provision in the House version of the bill that pertains directly to New York violates the Byrd Rule. That measure would change the way the state collects money for Medicaid. That could suggest efforts by Senate Majority Leader Mitch McConnell (R-Ky.) to offer state-specific changes to gain support for the bill might meet the same fate.
Minority Leader Chuck Schumer (D-N.Y.) said that decision could have “the greatest effect on Republicans’ ability to pass this bill.” He predicted it would “tie the majority leader’s hands as he tries to win over reluctant Republicans.”
Some of the provisions that didn’t pass muster with Ms. MacDonough were key to getting the bill through the House. And if they are dropped, it might make it difficult for the House to approve a final version of the bill.
Not all the decisions went the Democrats’ way. Ms. MacDonough found that only a simple majority is needed for language allowing states to impose work requirements for Medicaid recipients. She also said that a provision that will ban abortions if the services are paid through a new fund provided to states would be allowed. That’s because that fund will be governed by existing rules that already ban abortion in most cases.
A few provisions remain under review, according to the list. Those include allowing states to waive a long list of insurance protections, including the ACA’s essential health benefits and preexisting coverage guarantees. Also still under review is language allowing small businesses to pool together to purchase insurance as well as a provision changing requirements related to how much more insurers can charge older adults.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Novel knee osteoarthritis drugs target pain, joint space narrowing
MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.
In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.
These findings suggest that both could be future alternatives to using nonsteroidal anti-inflammatory drugs (NSAIDs), injected corticosteroids, and opioid analgesics, which are currently used to help manage knee OA.
Synthetic trans-capsaicin CNTX-4975
“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.
CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.
The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m2, and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.
The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.
The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).
“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.
The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.
A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).
“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.
Wnt inhibitor SM04690
Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.
Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.
SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.
Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.
In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.
Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.
A total of 455 subjects, mean age 60 years, were randomized into the trial.
Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.
An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.
The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).
However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.
Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.
“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.
The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.
MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.
In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.
These findings suggest that both could be future alternatives to using nonsteroidal anti-inflammatory drugs (NSAIDs), injected corticosteroids, and opioid analgesics, which are currently used to help manage knee OA.
Synthetic trans-capsaicin CNTX-4975
“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.
CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.
The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m2, and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.
The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.
The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).
“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.
The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.
A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).
“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.
Wnt inhibitor SM04690
Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.
Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.
SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.
Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.
In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.
Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.
A total of 455 subjects, mean age 60 years, were randomized into the trial.
Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.
An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.
The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).
However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.
Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.
“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.
The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.
MADRID – Two independently conducted, randomized, phase 2 trials of novel agents for moderate to severe knee osteoarthritis have produced promising results, as reported at the European Congress of Rheumatology.
In the 24-week, dose-ranging TRIUMPH trial involving 175 patients, treatment with the synthetic trans-capsaicin CNTX-4975 was associated with improvements in several clinical parameters, such as pain when walking, knee stiffness, and physical function, as well as being generally well tolerated.
These findings suggest that both could be future alternatives to using nonsteroidal anti-inflammatory drugs (NSAIDs), injected corticosteroids, and opioid analgesics, which are currently used to help manage knee OA.
Synthetic trans-capsaicin CNTX-4975
“Few effective pharmacologic therapies are available to manage the chronic pain of OA,” said Randall Stevens, MD, chief medical officer for Centrexion Therapeutics (Boston), the company developing CNTX-4975. Both NSAIDs and corticosteroids are associated with substantial toxicities, he argued, and opioid analgesics are not ideal to use long term because of the risk of side effects and addiction.
CNTX-4975 is a nonopioid analgesic that acts directly on the pain fibers in the knee, Dr. Stevens explained. Specifically, after a single injection, it targets the capsaicin receptor (transient receptor potential vanilloid 1, TRPV1) to inactivate only the local fibers transmitting pain signals to the brain. It does not affect other sensory fibers involved in sensation to touch or pressure, he said.
The aim of the phase 2b TRIUMPH trial was to examine the efficacy and safety of two doses (0.5 mg and 1.0 mg) of the synthetic trans-capsaicin versus placebo in patients with chronic, stable, moderate to severe knee OA who had been experiencing knee pain for at least 2 months or more. For inclusion, patients could be aged between 45 and 80 years, have a body mass index of up to 45 kg/m2, and had to have failed treatment or not be able to tolerate oral or intra-articular analgesics. Patients who had undergone recent knee surgery were excluded.
The primary endpoint was the change in pain with walking from baseline to week 12 measured as the area under the curve (AUC) for daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 score. Significant improvements were seen, with a least squares mean difference (LSMD) of –0.8 (P = .07) and –1.6 (P less than .0001) with the 0.5 mg and 1.0 mg doses of CNTX-4975, respectively, versus placebo.
The effects of CNTX-4975 were maintained to 24 weeks, Dr. Stevens reported, with significant improvements in pain with walking, comparing the 1.0-mg dose with placebo (LSMD, –1.35; P = .0002).
“These are the largest effect sizes I’ve seen with osteoarthritis knee pain,” Dr. Stevens said.
The investigators saw improvements in other efficacy endpoints, such as the weekly pain with walking (WOMAC A1) score and the change in weekly average joint stiffness (WOMAC B subscale, LSMD: −2.5; P = .0013) and physical function (WOMAC C subscale, LSMD: −18.3; P = .004) versus placebo at week 12. Numerically greater improvements occurred at week 24.
A similar percentage of patients experienced any treatment-emergent adverse events in the 1.0-mg (29.6%) CNTX-4975 treated and placebo groups (30%). Although a higher percentage of patients given the lower CNTX-4975 dose reported side effects (47.1%), most were mild to moderate and were considered unrelated to study treatment. Arthralgia was the most common side effect with CNTX-4975 1.0 mg versus placebo (7% vs. 5.7%).
“With these findings, we are moving in to phase 3 with the 1.0-mg dose,” Dr. Stevens said.
Wnt inhibitor SM04690
Promising data from the phase 2 trial of the Wnt inhibitor SM04690 also suggest that it, too, could soon be heading into phase 3 trials.
Several early clinical studies have been completed already, noted Yusuf Yazici, MD, chief medical officer of Samumed (San Diego), the California-based company that is developing SMO4690.
SM04690 is a small molecule inhibitor of the Wnt pathway, which is involved in increased bone formation and turnover, he explained. The hypothesis is that by blocking this pathway, the joint can be protected and cartilage could perhaps be regenerated.
Dr. Yazici presented radiographic outcomes at 26 weeks from a 52-week trial that “demonstrated SM04690 treatment maintained or increased medial joint space width compared to placebo.” This is important, as “joint space narrowing is indicative of OA progression and is predictive of knee surgery,” and radiographic progression remains a “gold standard” for assessing potential disease modification in OA, said Dr. Yazici, who is also clinical associate professor and director of the Seligman Center for Advanced Therapeutics at New York University.
In the phase 2 trial he presented, three doses of SM04690 (0.03 mg, 0.07 mg, and 0.23 mg), given as one 2-mL intra-articular injection into a single target knee, were tested and compared against placebo. The target knee was the knee designated as causing the patient the most pain, according to the study investigator.
Radiographs of both knees were taken at the start of treatment, at week 26, and again at week 52, with the change in medial joint space width analyzed. Clinical assessments included changes in WOMAC total, function, and pain subscale scores, and patients’ and physicians’ global assessments.
A total of 455 subjects, mean age 60 years, were randomized into the trial.
Considering all patients, the mean increase in medial joint space width from baseline to 26-week assessment versus placebo was –0.07 mm in the SM04690 0.03-mg group, –0.16 mm in the SM04690 0.07-mg group, and –0.03 mm in the SM04690 0.23-mg group.
An improvement in mean medial joint space narrowing was observed in 47.6% with SM04690 0.03 mg, 40.5% with 0.07 mg, 39.6% with 0.23 mg, and 30.5% with placebo. There was no change in a respective 7.6%, 9%, 17.8%, and 11.4%, and narrowing in the remainder (44.8%, 50.5%, 42,6%, and 58.1%) in this intent-to-treat population.
The investigators conducted prespecified subanalyses in a “unilateral symptomatic” population of 164 patients, and this showed slightly better results, with a higher probability of improved medial joint space width with SM04690 than with placebo (odds ratio, 5.2; 95% confidence interval, 2.1-12.8; P less than .001).
However, an important limitation of the study is that it was not formerly powered to look at radiographic progression, Dr. Yazici said. Nevertheless, radiographs were centrally read and high intra- and inter-observer reproducibility was observed.
Safety and clinical outcomes from the trial, which were reported separately in a poster at the meeting, showed no undue concerns and clinically meaningful improvements in both patients’ and physicians’ global assessments of pain with SM04690 versus placebo.
“Radiographic and clinical outcomes from this 26-week interim analysis of a 52-week trial suggest that SM04690 has potential as a disease-modifying osteoarthritis drug (DMOAD) for knee OA,” Dr. Yazici concluded.
The studies were supported by Samumed and by Centrexion Therapeutics. Dr. Yazici is an employee and shareholder of Samumed. Dr. Stevens is an employee and shareholder of Centrexion Therapeutics.
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Radiographic joint space narrowing was no worse or improved after treatment with the Wnt pathway inhibitor SM04690. Treatment with the synthetic trans-capsaicin CNTX-4975 improved pain when walking, knee stiffness, and physical function.
Data source: Two independently conducted randomized, phase 2 trials of patients with moderate to severe knee OA: a 52-week trial with SM04690 in 455 patients and a 24-week trial of CNTX-4975 in 175 patients.
Disclosures: Samumed and Centrexion Therapeutics sponsored the two separate studies. The presenting authors were employees and shareholders of their respective companies.
Meta-analysis shows correlation between diabetes and erectile dysfunction
WASHINGTON – More than half of men with type 1 or type 2 diabetes develop erectile dysfunction, making them more than three times as likely to develop ED, compared with healthy men, according to a systematic review of diabetes studies.
Data on the exact prevalence of erectile dysfunction in this population has been lacking until now. More precise figures are available from a meta-analysis of 145 studies taken from international diabetes databases.
In terms of risk, men with diabetes were 3.62 (95% CI, 2.53-5.16; P less than .0001) times more likely to develop ED, compared with healthy controls, according to investigators (Diabet Med. 2017 Jul 18. doi: 10.1111/dme.13403).
“Regarding sexual activity and the psychological impact of erectile dysfunction in men with diabetes mellitus, significant and positive associations have been found between depressive symptoms and erectile dysfunction,” said Youssef Kouidrat, MD, PhD, of the department of psychosis studies, Institute of Psychiatry, King’s College London, and his fellow researchers. “Therefore, early detection of erectile dysfunction is essential to improve the psychological health and men’s quality of life.”
Given ED’s serious effects on patients’ physical and emotional well being, it is essential for physicians to have a better understanding of the root causes of the condition in order to help patients as soon as possible, wrote the investigators.
The studies included in the meta-analysis represented a population of 88.755 men with an average age of 56 years, with dates of the studies ranging from the inception of the databases they were taken from up until November 2016.
A majority of the studies included were conducted in Asia (61), followed by Europe (48), North America (17), Africa (15), and Oceania, South America, and multiple continents (4 in total).
South America reported the highest prevalence of ED (74.6%), while the lowest prevalence reported was among studies in North America (34.5%).
Patients who were assessed using the Sexual Health Inventory for Men (SHIM) score reported a higher ED prevalence (82.2%), as did men above the age of 60 years old (62.2%).
With ED correlated to cardiovascular health and mortality, investigators advise physicians to keep testing in mind when assessing patients’ cardiovascular risk.
This study was limited by incomplete data from studies included, which made it difficult to determine prevalence by certain categories.
Other limitations included the lack of separation between type 1 and type 2 diabetes among many of the studies analyzed, as well as a lack of information from the studies analyzed on other risk factors concerning diabetes-related erectile dysfunction.
Investigators reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
WASHINGTON – More than half of men with type 1 or type 2 diabetes develop erectile dysfunction, making them more than three times as likely to develop ED, compared with healthy men, according to a systematic review of diabetes studies.
Data on the exact prevalence of erectile dysfunction in this population has been lacking until now. More precise figures are available from a meta-analysis of 145 studies taken from international diabetes databases.
In terms of risk, men with diabetes were 3.62 (95% CI, 2.53-5.16; P less than .0001) times more likely to develop ED, compared with healthy controls, according to investigators (Diabet Med. 2017 Jul 18. doi: 10.1111/dme.13403).
“Regarding sexual activity and the psychological impact of erectile dysfunction in men with diabetes mellitus, significant and positive associations have been found between depressive symptoms and erectile dysfunction,” said Youssef Kouidrat, MD, PhD, of the department of psychosis studies, Institute of Psychiatry, King’s College London, and his fellow researchers. “Therefore, early detection of erectile dysfunction is essential to improve the psychological health and men’s quality of life.”
Given ED’s serious effects on patients’ physical and emotional well being, it is essential for physicians to have a better understanding of the root causes of the condition in order to help patients as soon as possible, wrote the investigators.
The studies included in the meta-analysis represented a population of 88.755 men with an average age of 56 years, with dates of the studies ranging from the inception of the databases they were taken from up until November 2016.
A majority of the studies included were conducted in Asia (61), followed by Europe (48), North America (17), Africa (15), and Oceania, South America, and multiple continents (4 in total).
South America reported the highest prevalence of ED (74.6%), while the lowest prevalence reported was among studies in North America (34.5%).
Patients who were assessed using the Sexual Health Inventory for Men (SHIM) score reported a higher ED prevalence (82.2%), as did men above the age of 60 years old (62.2%).
With ED correlated to cardiovascular health and mortality, investigators advise physicians to keep testing in mind when assessing patients’ cardiovascular risk.
This study was limited by incomplete data from studies included, which made it difficult to determine prevalence by certain categories.
Other limitations included the lack of separation between type 1 and type 2 diabetes among many of the studies analyzed, as well as a lack of information from the studies analyzed on other risk factors concerning diabetes-related erectile dysfunction.
Investigators reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
WASHINGTON – More than half of men with type 1 or type 2 diabetes develop erectile dysfunction, making them more than three times as likely to develop ED, compared with healthy men, according to a systematic review of diabetes studies.
Data on the exact prevalence of erectile dysfunction in this population has been lacking until now. More precise figures are available from a meta-analysis of 145 studies taken from international diabetes databases.
In terms of risk, men with diabetes were 3.62 (95% CI, 2.53-5.16; P less than .0001) times more likely to develop ED, compared with healthy controls, according to investigators (Diabet Med. 2017 Jul 18. doi: 10.1111/dme.13403).
“Regarding sexual activity and the psychological impact of erectile dysfunction in men with diabetes mellitus, significant and positive associations have been found between depressive symptoms and erectile dysfunction,” said Youssef Kouidrat, MD, PhD, of the department of psychosis studies, Institute of Psychiatry, King’s College London, and his fellow researchers. “Therefore, early detection of erectile dysfunction is essential to improve the psychological health and men’s quality of life.”
Given ED’s serious effects on patients’ physical and emotional well being, it is essential for physicians to have a better understanding of the root causes of the condition in order to help patients as soon as possible, wrote the investigators.
The studies included in the meta-analysis represented a population of 88.755 men with an average age of 56 years, with dates of the studies ranging from the inception of the databases they were taken from up until November 2016.
A majority of the studies included were conducted in Asia (61), followed by Europe (48), North America (17), Africa (15), and Oceania, South America, and multiple continents (4 in total).
South America reported the highest prevalence of ED (74.6%), while the lowest prevalence reported was among studies in North America (34.5%).
Patients who were assessed using the Sexual Health Inventory for Men (SHIM) score reported a higher ED prevalence (82.2%), as did men above the age of 60 years old (62.2%).
With ED correlated to cardiovascular health and mortality, investigators advise physicians to keep testing in mind when assessing patients’ cardiovascular risk.
This study was limited by incomplete data from studies included, which made it difficult to determine prevalence by certain categories.
Other limitations included the lack of separation between type 1 and type 2 diabetes among many of the studies analyzed, as well as a lack of information from the studies analyzed on other risk factors concerning diabetes-related erectile dysfunction.
Investigators reported no relevant financial disclosures.
[email protected]
On Twitter @eaztweets
FROM DIABETIC MEDICINE
Key clinical point:
Major finding: Men with diabetes showed an odds ratio of 3.62 (95% CI, 2.53-5.16; P less than .0001) of developing erectile dysfunction, compared with healthy controls.
Data source: An analysis of 145 studies representing 88,577 men from international databases spanning from creation of the database to November 2016.
Disclosures: Investigators report no relevant financial disclosures.
Painful autoimmune neuropathy may mimic Guillain-Barré syndrome
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
FROM MUSCLE & NERVE
5 ways White House can use its muscle to undercut Obamacare
President Donald Trump has vowed to “let Obamacare fail,” after legislative efforts to undo the Affordable Care Act have stalled.
He and congressional Republicans have repeatedly portrayed the Affordable Care Act insurance marketplaces, also known as exchanges, as being in a “death spiral.” But independent analyses have concluded that such spontaneous disintegration isn’t happening.
In a number of ways, the Trump administration’s policies are pushing Obamacare into the vortex.
Reports from Standard & Poor’s, the Congressional Budget Office and the Kaiser Family Foundation all suggest that the exchanges – where people can shop for coverage, often with the help of a government subsidy – are stabilizing. (Kaiser Health News is an editorially independent program of the foundation.)
“The administration has a lot of power to undermine the markets and make them dysfunctional,” said Sabrina Corlette, a research professor at Georgetown University’s Center on Health Insurance Reforms, who specializes in private insurance markets.
Here’s a look at five ways the White House is already working to weaken the health law, and what that means for consumers.
‘Cost-sharing reductions’
Under the ACA, when someone’s income falls between 100% and 250% of the federal poverty level – up to about $29,000 for an individual or around $61,000 for a family of four – marketplace carriers must offer a plan with “cost-sharing reductions” (CSRs) that reduce consumers’ out-of-pocket expenses.
Reducing cost-sharing – generally copayments and deductibles – makes plans more expensive for the insurers. The Obama administration used its rule-making power to set up direct payments to carriers to help offset this burden. The Trump White House has inherited that responsibility but also has the power to end the payment program.
The nonpartisan Congressional Budget Office estimated CSR subsidies in 2017 would total about $7 billion. Without that money, analysts say, more insurers might choose to exit, limiting options for consumers, and letting the insurers who remain charge higher prices.
Trump has been committedly noncommittal, publicly indicating he would like to halt the subsidies, but so far – on a month-to-month basis – letting them continue.
The uncertainty makes insurance companies skittish about participating, analysts noted. It’s also one reason some plans say they have had to increase their rates, noted Charles Gaba, a Michigan-based blogger who tracks ACA sign-ups. For instance: When filing plans for the 2018 marketplace, carriers on average raised premiums by about 34% – with about 20 points stemming from CSR uncertainty, Mr. Gaba said, based on an analysis of 21 states’ initial rate filings. Dropping the subsidies altogether would be even more damaging.
Weaken the mandate
The White House has already signaled it does not want to enforce the individual mandate – the health law’s requirement that all people have coverage. And administration officials have repeated that position.
Meanwhile, in January, it issued an executive order that encouraged U.S. agencies to grant exemptions and waive or defer health law provisions that could put financial strain on companies or individuals – which could also be applied to the individual mandate.
For 2016 tax returns, though, the Internal Revenue Service continued to impose a financial penalty on people who didn’t have health insurance and who didn’t qualify for an exemption.
But enforcement may be waning. This year, the IRS was supposed to reject tax returns if people didn’t indicate whether they had coverage, flagging them for a potential penalty. Instead, it continued processing them, citing Trump’s executive order.
If the IRS has already processed any tax refunds for consumers, then they “don’t have much leverage” when attempting to collect the mandate fee, said Timothy Jost, emeritus law professor at Washington and Lee University in Virginia and an expert on health reform.
Enforcement of the mandate, economists note, is crucial to ensuring that enough healthy people buy coverage to balance the costs of sicker beneficiaries.
But even with the mandate in effect, the efforts to defang it bring confusion.
“A lot of people believe the Trump administration is not enforcing it,” Mr. Jost said.
As a result, healthy people may become less likely to buy insurance, even as sick ones continue seeking it. That means higher prices, and a shakier pool.
“If they don’t think they’re going to get healthy people in the risk pool, they’re going to increase their rates further to protect themselves,” Mr. Jost said. “And as they raise their rates further to protect themselves, people … start to drop out.”
Thus, the president’s position on the mandate is leaving insurance carriers and commissioners “apprehensive,” noted Mike Kreidler, Washington state’s insurance commissioner.
A bare market
Skittishness on the part of insurers could lead them to drop out of some marketplaces, leaving consumers in some areas with few or no choices. Those “bare markets” are possible under even stable circumstances – and preventing them requires active federal involvement.
Under the Obama administration, high-level officials were “on the phone daily with insurance company executives … trying to get them to participate,” Ms. Corlette said. “It was very much an all-hands-on-deck, ‘we’re going to make it work for you guys’ kind of communication.”
And so far Trump’s Department of Health and Human Services doesn’t appear to be emphasizing this kind of essential outreach, both Ms. Corlette and Mr. Jost suggested. A few months ago, Mr. Kreidler agreed, HHS staffers appeared interested in helping states fill their bare counties – but that support has since dwindled.
“This may be sort of under the radar, but it can have real, lasting effects” for consumer choice, Ms. Corlette said.
All quiet on the enrollment front
The administration could further undermine the marketplace by dropping outreach to consumers. It’s already a shorter enrollment period this year – spanning 6 weeks instead of 3 months, from Nov. 1 to Dec. 15 – though that change was already slated to eventually take effect.
That shorter period means people may miss the memo on signing up – or at least need an extra push, Ms. Corlette said. And that’s another way the administration could undermine the marketplaces: simply choosing not to advertise them.
Last sign-up season, HHS stopped open enrollment advertising in January, pulling ads a few days before the period ended. Enrollment dropped compared with previous years, Mr. Jost and Mr. Gaba noted, with young, healthy people being more likely not to buy coverage.
The administration also just stopped funding federal contractors that supported efforts by community groups and other organizations in some of the nation’s largest cities to sign up people.
Dropping advertising, shortening open enrollment, or simply scaling back on technical maintenance for the marketplace website could all have significant impact, Ms. Corlette said. People who are sick and need insurance will likely seek it out, but those who are healthier – for whom health insurance is a less pressing priority – could miss the boat.
Again, Mr. Jost said, that affects insurer participation.
“Insurance is a product that needs to be sold,” he said. “If the insurers believe they’re not going to get any help at all in marketing their product,” he added, fewer will want to enter the marketplace.
Word of (bad) mouth
HHS has taken an active role in criticizing the health law – pushing press releases and videos that argue it has helped more than hurt. That strategy could do a lot of harm, experts said.
If consumers keep hearing the law is failing, Mr. Jost noted, some will ultimately believe it, buying coverage only if they need it and thereby skewing the insurance risk pool.
Perceived hostility also has an effect on insurers, steering them away from marketplace participation.
“When you undermine confidence in the marketplace, you don’t need a Ph.D. in economics to know it’s not good long term,” Ms. Corlette said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
President Donald Trump has vowed to “let Obamacare fail,” after legislative efforts to undo the Affordable Care Act have stalled.
He and congressional Republicans have repeatedly portrayed the Affordable Care Act insurance marketplaces, also known as exchanges, as being in a “death spiral.” But independent analyses have concluded that such spontaneous disintegration isn’t happening.
In a number of ways, the Trump administration’s policies are pushing Obamacare into the vortex.
Reports from Standard & Poor’s, the Congressional Budget Office and the Kaiser Family Foundation all suggest that the exchanges – where people can shop for coverage, often with the help of a government subsidy – are stabilizing. (Kaiser Health News is an editorially independent program of the foundation.)
“The administration has a lot of power to undermine the markets and make them dysfunctional,” said Sabrina Corlette, a research professor at Georgetown University’s Center on Health Insurance Reforms, who specializes in private insurance markets.
Here’s a look at five ways the White House is already working to weaken the health law, and what that means for consumers.
‘Cost-sharing reductions’
Under the ACA, when someone’s income falls between 100% and 250% of the federal poverty level – up to about $29,000 for an individual or around $61,000 for a family of four – marketplace carriers must offer a plan with “cost-sharing reductions” (CSRs) that reduce consumers’ out-of-pocket expenses.
Reducing cost-sharing – generally copayments and deductibles – makes plans more expensive for the insurers. The Obama administration used its rule-making power to set up direct payments to carriers to help offset this burden. The Trump White House has inherited that responsibility but also has the power to end the payment program.
The nonpartisan Congressional Budget Office estimated CSR subsidies in 2017 would total about $7 billion. Without that money, analysts say, more insurers might choose to exit, limiting options for consumers, and letting the insurers who remain charge higher prices.
Trump has been committedly noncommittal, publicly indicating he would like to halt the subsidies, but so far – on a month-to-month basis – letting them continue.
The uncertainty makes insurance companies skittish about participating, analysts noted. It’s also one reason some plans say they have had to increase their rates, noted Charles Gaba, a Michigan-based blogger who tracks ACA sign-ups. For instance: When filing plans for the 2018 marketplace, carriers on average raised premiums by about 34% – with about 20 points stemming from CSR uncertainty, Mr. Gaba said, based on an analysis of 21 states’ initial rate filings. Dropping the subsidies altogether would be even more damaging.
Weaken the mandate
The White House has already signaled it does not want to enforce the individual mandate – the health law’s requirement that all people have coverage. And administration officials have repeated that position.
Meanwhile, in January, it issued an executive order that encouraged U.S. agencies to grant exemptions and waive or defer health law provisions that could put financial strain on companies or individuals – which could also be applied to the individual mandate.
For 2016 tax returns, though, the Internal Revenue Service continued to impose a financial penalty on people who didn’t have health insurance and who didn’t qualify for an exemption.
But enforcement may be waning. This year, the IRS was supposed to reject tax returns if people didn’t indicate whether they had coverage, flagging them for a potential penalty. Instead, it continued processing them, citing Trump’s executive order.
If the IRS has already processed any tax refunds for consumers, then they “don’t have much leverage” when attempting to collect the mandate fee, said Timothy Jost, emeritus law professor at Washington and Lee University in Virginia and an expert on health reform.
Enforcement of the mandate, economists note, is crucial to ensuring that enough healthy people buy coverage to balance the costs of sicker beneficiaries.
But even with the mandate in effect, the efforts to defang it bring confusion.
“A lot of people believe the Trump administration is not enforcing it,” Mr. Jost said.
As a result, healthy people may become less likely to buy insurance, even as sick ones continue seeking it. That means higher prices, and a shakier pool.
“If they don’t think they’re going to get healthy people in the risk pool, they’re going to increase their rates further to protect themselves,” Mr. Jost said. “And as they raise their rates further to protect themselves, people … start to drop out.”
Thus, the president’s position on the mandate is leaving insurance carriers and commissioners “apprehensive,” noted Mike Kreidler, Washington state’s insurance commissioner.
A bare market
Skittishness on the part of insurers could lead them to drop out of some marketplaces, leaving consumers in some areas with few or no choices. Those “bare markets” are possible under even stable circumstances – and preventing them requires active federal involvement.
Under the Obama administration, high-level officials were “on the phone daily with insurance company executives … trying to get them to participate,” Ms. Corlette said. “It was very much an all-hands-on-deck, ‘we’re going to make it work for you guys’ kind of communication.”
And so far Trump’s Department of Health and Human Services doesn’t appear to be emphasizing this kind of essential outreach, both Ms. Corlette and Mr. Jost suggested. A few months ago, Mr. Kreidler agreed, HHS staffers appeared interested in helping states fill their bare counties – but that support has since dwindled.
“This may be sort of under the radar, but it can have real, lasting effects” for consumer choice, Ms. Corlette said.
All quiet on the enrollment front
The administration could further undermine the marketplace by dropping outreach to consumers. It’s already a shorter enrollment period this year – spanning 6 weeks instead of 3 months, from Nov. 1 to Dec. 15 – though that change was already slated to eventually take effect.
That shorter period means people may miss the memo on signing up – or at least need an extra push, Ms. Corlette said. And that’s another way the administration could undermine the marketplaces: simply choosing not to advertise them.
Last sign-up season, HHS stopped open enrollment advertising in January, pulling ads a few days before the period ended. Enrollment dropped compared with previous years, Mr. Jost and Mr. Gaba noted, with young, healthy people being more likely not to buy coverage.
The administration also just stopped funding federal contractors that supported efforts by community groups and other organizations in some of the nation’s largest cities to sign up people.
Dropping advertising, shortening open enrollment, or simply scaling back on technical maintenance for the marketplace website could all have significant impact, Ms. Corlette said. People who are sick and need insurance will likely seek it out, but those who are healthier – for whom health insurance is a less pressing priority – could miss the boat.
Again, Mr. Jost said, that affects insurer participation.
“Insurance is a product that needs to be sold,” he said. “If the insurers believe they’re not going to get any help at all in marketing their product,” he added, fewer will want to enter the marketplace.
Word of (bad) mouth
HHS has taken an active role in criticizing the health law – pushing press releases and videos that argue it has helped more than hurt. That strategy could do a lot of harm, experts said.
If consumers keep hearing the law is failing, Mr. Jost noted, some will ultimately believe it, buying coverage only if they need it and thereby skewing the insurance risk pool.
Perceived hostility also has an effect on insurers, steering them away from marketplace participation.
“When you undermine confidence in the marketplace, you don’t need a Ph.D. in economics to know it’s not good long term,” Ms. Corlette said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
President Donald Trump has vowed to “let Obamacare fail,” after legislative efforts to undo the Affordable Care Act have stalled.
He and congressional Republicans have repeatedly portrayed the Affordable Care Act insurance marketplaces, also known as exchanges, as being in a “death spiral.” But independent analyses have concluded that such spontaneous disintegration isn’t happening.
In a number of ways, the Trump administration’s policies are pushing Obamacare into the vortex.
Reports from Standard & Poor’s, the Congressional Budget Office and the Kaiser Family Foundation all suggest that the exchanges – where people can shop for coverage, often with the help of a government subsidy – are stabilizing. (Kaiser Health News is an editorially independent program of the foundation.)
“The administration has a lot of power to undermine the markets and make them dysfunctional,” said Sabrina Corlette, a research professor at Georgetown University’s Center on Health Insurance Reforms, who specializes in private insurance markets.
Here’s a look at five ways the White House is already working to weaken the health law, and what that means for consumers.
‘Cost-sharing reductions’
Under the ACA, when someone’s income falls between 100% and 250% of the federal poverty level – up to about $29,000 for an individual or around $61,000 for a family of four – marketplace carriers must offer a plan with “cost-sharing reductions” (CSRs) that reduce consumers’ out-of-pocket expenses.
Reducing cost-sharing – generally copayments and deductibles – makes plans more expensive for the insurers. The Obama administration used its rule-making power to set up direct payments to carriers to help offset this burden. The Trump White House has inherited that responsibility but also has the power to end the payment program.
The nonpartisan Congressional Budget Office estimated CSR subsidies in 2017 would total about $7 billion. Without that money, analysts say, more insurers might choose to exit, limiting options for consumers, and letting the insurers who remain charge higher prices.
Trump has been committedly noncommittal, publicly indicating he would like to halt the subsidies, but so far – on a month-to-month basis – letting them continue.
The uncertainty makes insurance companies skittish about participating, analysts noted. It’s also one reason some plans say they have had to increase their rates, noted Charles Gaba, a Michigan-based blogger who tracks ACA sign-ups. For instance: When filing plans for the 2018 marketplace, carriers on average raised premiums by about 34% – with about 20 points stemming from CSR uncertainty, Mr. Gaba said, based on an analysis of 21 states’ initial rate filings. Dropping the subsidies altogether would be even more damaging.
Weaken the mandate
The White House has already signaled it does not want to enforce the individual mandate – the health law’s requirement that all people have coverage. And administration officials have repeated that position.
Meanwhile, in January, it issued an executive order that encouraged U.S. agencies to grant exemptions and waive or defer health law provisions that could put financial strain on companies or individuals – which could also be applied to the individual mandate.
For 2016 tax returns, though, the Internal Revenue Service continued to impose a financial penalty on people who didn’t have health insurance and who didn’t qualify for an exemption.
But enforcement may be waning. This year, the IRS was supposed to reject tax returns if people didn’t indicate whether they had coverage, flagging them for a potential penalty. Instead, it continued processing them, citing Trump’s executive order.
If the IRS has already processed any tax refunds for consumers, then they “don’t have much leverage” when attempting to collect the mandate fee, said Timothy Jost, emeritus law professor at Washington and Lee University in Virginia and an expert on health reform.
Enforcement of the mandate, economists note, is crucial to ensuring that enough healthy people buy coverage to balance the costs of sicker beneficiaries.
But even with the mandate in effect, the efforts to defang it bring confusion.
“A lot of people believe the Trump administration is not enforcing it,” Mr. Jost said.
As a result, healthy people may become less likely to buy insurance, even as sick ones continue seeking it. That means higher prices, and a shakier pool.
“If they don’t think they’re going to get healthy people in the risk pool, they’re going to increase their rates further to protect themselves,” Mr. Jost said. “And as they raise their rates further to protect themselves, people … start to drop out.”
Thus, the president’s position on the mandate is leaving insurance carriers and commissioners “apprehensive,” noted Mike Kreidler, Washington state’s insurance commissioner.
A bare market
Skittishness on the part of insurers could lead them to drop out of some marketplaces, leaving consumers in some areas with few or no choices. Those “bare markets” are possible under even stable circumstances – and preventing them requires active federal involvement.
Under the Obama administration, high-level officials were “on the phone daily with insurance company executives … trying to get them to participate,” Ms. Corlette said. “It was very much an all-hands-on-deck, ‘we’re going to make it work for you guys’ kind of communication.”
And so far Trump’s Department of Health and Human Services doesn’t appear to be emphasizing this kind of essential outreach, both Ms. Corlette and Mr. Jost suggested. A few months ago, Mr. Kreidler agreed, HHS staffers appeared interested in helping states fill their bare counties – but that support has since dwindled.
“This may be sort of under the radar, but it can have real, lasting effects” for consumer choice, Ms. Corlette said.
All quiet on the enrollment front
The administration could further undermine the marketplace by dropping outreach to consumers. It’s already a shorter enrollment period this year – spanning 6 weeks instead of 3 months, from Nov. 1 to Dec. 15 – though that change was already slated to eventually take effect.
That shorter period means people may miss the memo on signing up – or at least need an extra push, Ms. Corlette said. And that’s another way the administration could undermine the marketplaces: simply choosing not to advertise them.
Last sign-up season, HHS stopped open enrollment advertising in January, pulling ads a few days before the period ended. Enrollment dropped compared with previous years, Mr. Jost and Mr. Gaba noted, with young, healthy people being more likely not to buy coverage.
The administration also just stopped funding federal contractors that supported efforts by community groups and other organizations in some of the nation’s largest cities to sign up people.
Dropping advertising, shortening open enrollment, or simply scaling back on technical maintenance for the marketplace website could all have significant impact, Ms. Corlette said. People who are sick and need insurance will likely seek it out, but those who are healthier – for whom health insurance is a less pressing priority – could miss the boat.
Again, Mr. Jost said, that affects insurer participation.
“Insurance is a product that needs to be sold,” he said. “If the insurers believe they’re not going to get any help at all in marketing their product,” he added, fewer will want to enter the marketplace.
Word of (bad) mouth
HHS has taken an active role in criticizing the health law – pushing press releases and videos that argue it has helped more than hurt. That strategy could do a lot of harm, experts said.
If consumers keep hearing the law is failing, Mr. Jost noted, some will ultimately believe it, buying coverage only if they need it and thereby skewing the insurance risk pool.
Perceived hostility also has an effect on insurers, steering them away from marketplace participation.
“When you undermine confidence in the marketplace, you don’t need a Ph.D. in economics to know it’s not good long term,” Ms. Corlette said.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
The VA Is in Critical Condition, but What Is the Prognosis?
In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.
For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.
Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.
Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.
Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?
Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.
He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.
The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.
Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.
I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.
Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.
In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.
For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.
Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.
Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.
Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?
Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.
He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.
The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.
Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.
I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.
Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.
In his first ever—and perhaps the first ever state of the VA—speech delivered on May 30, 2017, VA Secretary David J. Shulkin, MD, reported to the nation and Congress that “the VA is still in critical condition.” This medical metaphor reflects Dr. Shulkin’s distinction of being the only physician ever to hold this cabinet-level post.
For anyone in health care, such a reference immediately calls forth a variety of associations—most of them serious concerns for the status of the VA and whether it will survive. In this editorial, I will expand on this metaphor and explore its meaning for the future of the VA.
Dr. Shulkin extended the metaphor when he said that the “VA requires intensive care.” For clinicians, this remark tells us that the VA is either seriously ill or injured. Yet there is hope because the chief doctor of the VA reassures us that the patient—the largest health care system in the country—is improving. This improvement from critical care to intensive care status informs us that the VA was very sick, maybe even dying, during the previous administration in which Dr. Shulkin served as VA’s Under Secretary for Health.
Dr. Shulkin, a general internist who still sees primary care patients at the VA, gave us a diagnosis of the VA’s most serious symptoms: a lack of access to timely care, a high rate of veteran suicides, an inability to enforce employee accountability, multiple obstacles to hiring and retaining qualified staff, an unacceptable quality of care at some VAMCs, and a backlog of disability claims due to inefficient processing.
Dr. Shulkin also gave us a broad idea of his goal for care, “We are taking immediate and decisive steps stabilizing the organization.” But the more I thought about this impressive speech, the more I wondered, What is the VA’s actual diagnosis?
Several of the many news commentaries analyzing Shulkin’s State of the VA speech suggested possible etiologies. According to the Public Broadcasting Service (PBS), “In a ‘State of the VA’ report, Shulkin, a physician, issued a blunt diagnosis: ‘There is a lot of work to do.’” Astute clinicians will immediately recognize that PBS is right about the secretary’s honesty regarding the magnitude of the task facing him.
He was not providing a diagnosis as much as offering an indirect assessment of the patient’s condition. “A lot of work,” although not a diagnosis, is a colloquial description of the treatment plan that the secretary further outlined in his report. Like any good treatment plan, there is a direct correlation between the major symptoms of the disorder and the therapies that Dr. Shulkin prescribed.
The Secretary recommended and the President signed the Department of Veterans Affairs Accountability and Whistleblower Protection Act of 2017 on June 23, 2017, to make it easier to discipline and terminate VA employees who may be keeping the VA organization ill or at least preventing it from getting better. He also prescribed continued and even higher dose infusions of community care to treat the central access problem. In addition, Dr. Shulkin ordered that the most effective available interventions be used for suicide prevention, enhancement of the overall quality of care, and to improve accountability.
Even with the most efficacious treatments, a high-functioning intensive care unit needs state-of-theart technology and equipment. In a long-awaited announcement, Dr. Shulkin reported on June 5 that of 2 competing modalities to revive the VA’s ailing electronic health record system—the brain of our critical care patient—rather than repair the moribund CPRS, the VA will receive a transplant of the DoD MHS Genesis. Critical care, especially when delivered in a combat zone, requires difficult triage decisions. The secretary has made similar tough resource allocation decisions, determining that some of the VA’s oldest and most debilitated facilities will not be sustained in their present form.
I am near the end of this editorial and still do not have a diagnosis. Pundits, politicians, and policy specialists all have their differential diagnosis as well as veterans groups and VA employees.“Bloated bureaucracy” is the diagnosis from many of these VA critics. Dr. Shulkin proposed a remedy for this disease: He plans to consolidate the VA headquarters.
Even more important, for those who believe the VA should not have a DNR but be allowed to recover, what does the physician who holds the VA’s life in his hands believe is the prognosis for this 86-year-old institution? Dr. Shulkin expressed the hope that the VA can recover its health, saying he is “confident that we will be able turn VA into the organization veterans and their families deserve, and one that America can take pride in.” The most vehement of VA’s opponents would say that pouring additional millions of dollars into such a moribund entity is futile care. Yet the secretary and thousands of VA patients, staff, and supporters believe that the agency that President Lincoln created at the end of the bloodiest war in U.S. history still has value and can be restored to meaningful service for those who have, who are, and who will place their lives on the line for their country.
Statins for the Physically Fit: Do They Help or Hurt?
Statins may not be the best choice for physically active people, even short term. A study by researchers from VA North Texas Health Care System in Dallas, University of Texas in Austin, and Joint Base Antonio-Fort Sam in Houston, Texas, found higher risks of diabetes and diabetic complications—“without any of the hoped-for cardiovascular benefits.”
It is already established that statins can raise the risk of diabetes. But the military health researchers say there has been no primary prevention clinical trial to examine the overall adverse events (AEs) of statins in physically active people. In a previous study of TRICARE enrollees, the researchers found that short-term statin therapy was not associated with reduced cardiovascular morbidity but was associated with increased risk of AEs. To follow up on those findings, the researchers conducted another study to examine the short- and long-term AEs of statins in active-duty military—chosen precisely because of their physical fitness.
The study, which involved 837 statin users and 2,488 nonusers, covered 2001-2011. The researchers captured 3 intervals: short-term outcomes, 2006; intermediate outcomes, 2006-2009; and long-term outcomes, 2006-2011.
Statin users had nearly twice the risk of diabetes compared with nonusers: 12.5% vs 5.8%. They also had a higher incidence of diabetes with complications: 1.7% vs 0.7%. However, the overall incidence of major acute cardiovascular events was low: 2.58 events per 1,000 person-years in users, and 2.63 events in nonusers. That small number meant the researchers could not show beneficial cardiovascular effects due to statins.
Their findings help fill a gap in the literature, the researchers say, and highlight the possibility that some healthy and active individuals may be receiving statins unnecessarily, putting them at risk for AEs. Moreover, those risks persist long after statins are discontinued, the researchers note. Their study suggests that “we may need to adjust our approach and priorities to primary prevention.”
Source:
Mansi IA, English JL, Morris MJ, Zhang S, Mortensen EM, Halm EA. J Sci Med Sport. 2017;20(7):627-632.
doi: 10.1016/j.jsams.2016.12.075.
Statins may not be the best choice for physically active people, even short term. A study by researchers from VA North Texas Health Care System in Dallas, University of Texas in Austin, and Joint Base Antonio-Fort Sam in Houston, Texas, found higher risks of diabetes and diabetic complications—“without any of the hoped-for cardiovascular benefits.”
It is already established that statins can raise the risk of diabetes. But the military health researchers say there has been no primary prevention clinical trial to examine the overall adverse events (AEs) of statins in physically active people. In a previous study of TRICARE enrollees, the researchers found that short-term statin therapy was not associated with reduced cardiovascular morbidity but was associated with increased risk of AEs. To follow up on those findings, the researchers conducted another study to examine the short- and long-term AEs of statins in active-duty military—chosen precisely because of their physical fitness.
The study, which involved 837 statin users and 2,488 nonusers, covered 2001-2011. The researchers captured 3 intervals: short-term outcomes, 2006; intermediate outcomes, 2006-2009; and long-term outcomes, 2006-2011.
Statin users had nearly twice the risk of diabetes compared with nonusers: 12.5% vs 5.8%. They also had a higher incidence of diabetes with complications: 1.7% vs 0.7%. However, the overall incidence of major acute cardiovascular events was low: 2.58 events per 1,000 person-years in users, and 2.63 events in nonusers. That small number meant the researchers could not show beneficial cardiovascular effects due to statins.
Their findings help fill a gap in the literature, the researchers say, and highlight the possibility that some healthy and active individuals may be receiving statins unnecessarily, putting them at risk for AEs. Moreover, those risks persist long after statins are discontinued, the researchers note. Their study suggests that “we may need to adjust our approach and priorities to primary prevention.”
Source:
Mansi IA, English JL, Morris MJ, Zhang S, Mortensen EM, Halm EA. J Sci Med Sport. 2017;20(7):627-632.
doi: 10.1016/j.jsams.2016.12.075.
Statins may not be the best choice for physically active people, even short term. A study by researchers from VA North Texas Health Care System in Dallas, University of Texas in Austin, and Joint Base Antonio-Fort Sam in Houston, Texas, found higher risks of diabetes and diabetic complications—“without any of the hoped-for cardiovascular benefits.”
It is already established that statins can raise the risk of diabetes. But the military health researchers say there has been no primary prevention clinical trial to examine the overall adverse events (AEs) of statins in physically active people. In a previous study of TRICARE enrollees, the researchers found that short-term statin therapy was not associated with reduced cardiovascular morbidity but was associated with increased risk of AEs. To follow up on those findings, the researchers conducted another study to examine the short- and long-term AEs of statins in active-duty military—chosen precisely because of their physical fitness.
The study, which involved 837 statin users and 2,488 nonusers, covered 2001-2011. The researchers captured 3 intervals: short-term outcomes, 2006; intermediate outcomes, 2006-2009; and long-term outcomes, 2006-2011.
Statin users had nearly twice the risk of diabetes compared with nonusers: 12.5% vs 5.8%. They also had a higher incidence of diabetes with complications: 1.7% vs 0.7%. However, the overall incidence of major acute cardiovascular events was low: 2.58 events per 1,000 person-years in users, and 2.63 events in nonusers. That small number meant the researchers could not show beneficial cardiovascular effects due to statins.
Their findings help fill a gap in the literature, the researchers say, and highlight the possibility that some healthy and active individuals may be receiving statins unnecessarily, putting them at risk for AEs. Moreover, those risks persist long after statins are discontinued, the researchers note. Their study suggests that “we may need to adjust our approach and priorities to primary prevention.”
Source:
Mansi IA, English JL, Morris MJ, Zhang S, Mortensen EM, Halm EA. J Sci Med Sport. 2017;20(7):627-632.
doi: 10.1016/j.jsams.2016.12.075.
Tests reveal risk of passing on SCD, other diseases
Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.
The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).
Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).
Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.
In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.
QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.
The disorders covered by QHerit include:
| Disease | Race/ethnicity | |||
| Alpha-thalassemia | Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Beta-
hemoglobinopathies (including SCD) |
Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Bloom syndrome | Ashkenazi Jewish descent (AJ) | |||
| Canavan disease | AJ and non-AJ | |||
| Cystic fibrosis | African American, AJ, Asian American, Hispanic American, non-Hispanic Caucasian | |||
| Dihydrolipoamide
dehydrogenase deficiency |
AJ | |||
| Familial dysautonomia | AJ | |||
| Familial hyperinsulinism | AJ | |||
| Fanconi anemia Type C | AJ | |||
| Fragile X syndrome | Females | |||
| Gaucher disease | AJ | |||
| Glycogen storage
disease Type Ia |
AJ, Caucasian | |||
| Joubert syndrome 2 | AJ | |||
| Maple syrup urine
disease |
AJ | |||
| Mucolipidosis Type IV | AJ | |||
| Nemaline myopathy | AJ | |||
| Niemann-Pick
disease Types A & B |
AJ | |||
| Spinal muscular
atrophy |
African American, AJ, Asian, Caucasian, Hispanic | |||
| Tay-Sachs disease | AJ, French Canadian, general population | |||
| Usher syndrome,
Type IF |
AJ | |||
| Usher syndrome,
Type IIIA |
AJ | |||
| Walker-Warburg
syndrome |
AJ | |||
QHerit is now available for order by US physicians. For more information, visit www.QHerit.com. 
Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.
The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).
Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).
Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.
In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.
QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.
The disorders covered by QHerit include:
| Disease | Race/ethnicity | |||
| Alpha-thalassemia | Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Beta-
hemoglobinopathies (including SCD) |
Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Bloom syndrome | Ashkenazi Jewish descent (AJ) | |||
| Canavan disease | AJ and non-AJ | |||
| Cystic fibrosis | African American, AJ, Asian American, Hispanic American, non-Hispanic Caucasian | |||
| Dihydrolipoamide
dehydrogenase deficiency |
AJ | |||
| Familial dysautonomia | AJ | |||
| Familial hyperinsulinism | AJ | |||
| Fanconi anemia Type C | AJ | |||
| Fragile X syndrome | Females | |||
| Gaucher disease | AJ | |||
| Glycogen storage
disease Type Ia |
AJ, Caucasian | |||
| Joubert syndrome 2 | AJ | |||
| Maple syrup urine
disease |
AJ | |||
| Mucolipidosis Type IV | AJ | |||
| Nemaline myopathy | AJ | |||
| Niemann-Pick
disease Types A & B |
AJ | |||
| Spinal muscular
atrophy |
African American, AJ, Asian, Caucasian, Hispanic | |||
| Tay-Sachs disease | AJ, French Canadian, general population | |||
| Usher syndrome,
Type IF |
AJ | |||
| Usher syndrome,
Type IIIA |
AJ | |||
| Walker-Warburg
syndrome |
AJ | |||
QHerit is now available for order by US physicians. For more information, visit www.QHerit.com.
Quest Diagnostics has announced the US launch of QHerit™, a genetic screening service that helps people of multiple ethnicities identify their risk of passing on heritable disorders to their offspring.
The QHerit Pan-Ethnic Expanded Carrier Screen is a panel of tests for the 22 heritable diseases cited in new screening guidelines from the American College of Gynecology (ACOG).
Among the diseases are alpha-thalassemia, Fanconi anemia, and beta-hemoglobinopathies, including sickle cell disease (SCD).
Traditionally, genetic carrier screening has been used for at-risk populations based on specific ancestry assumptions and focused on only a few likely disorders with higher prevalence associated with that ethnicity.
In its new guidelines, ACOG recommends offering pan-ethnic, expanded carrier, and ethnic-specific screening for all women considering pregnancy. The guidelines also state that the partner of a woman who tests positive may be a candidate for screening.
QHerit screens women and men for clinically relevant variants of genes for disorders that could have potentially devastating consequences, result in early death, or create a need for significant early intervention.
The disorders covered by QHerit include:
| Disease | Race/ethnicity | |||
| Alpha-thalassemia | Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Beta-
hemoglobinopathies (including SCD) |
Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian | |||
| Bloom syndrome | Ashkenazi Jewish descent (AJ) | |||
| Canavan disease | AJ and non-AJ | |||
| Cystic fibrosis | African American, AJ, Asian American, Hispanic American, non-Hispanic Caucasian | |||
| Dihydrolipoamide
dehydrogenase deficiency |
AJ | |||
| Familial dysautonomia | AJ | |||
| Familial hyperinsulinism | AJ | |||
| Fanconi anemia Type C | AJ | |||
| Fragile X syndrome | Females | |||
| Gaucher disease | AJ | |||
| Glycogen storage
disease Type Ia |
AJ, Caucasian | |||
| Joubert syndrome 2 | AJ | |||
| Maple syrup urine
disease |
AJ | |||
| Mucolipidosis Type IV | AJ | |||
| Nemaline myopathy | AJ | |||
| Niemann-Pick
disease Types A & B |
AJ | |||
| Spinal muscular
atrophy |
African American, AJ, Asian, Caucasian, Hispanic | |||
| Tay-Sachs disease | AJ, French Canadian, general population | |||
| Usher syndrome,
Type IF |
AJ | |||
| Usher syndrome,
Type IIIA |
AJ | |||
| Walker-Warburg
syndrome |
AJ | |||
QHerit is now available for order by US physicians. For more information, visit www.QHerit.com.
Variation in physician spending and association with patient outcomes
Title: Variation in physician spending not associated with patient outcomes
Clinical Question: Is there a variation in spending between physicians in the same hospital, and does it have an effect on patient outcomes?
Background: Not much is known about the presence of variations in individual physician spending within the same hospital and it is not known if higher-spending physicians have better patient outcomes compared to peers within the same institution.
Setting: National sample of hospitalized Medicare beneficiaries.
Synopsis: Using National Medicare data over a 4-year period, the authors showed that there is wide variation in Part B spending across physicians (hospitalists and general internists) within the same acute care hospital. This inter-physician variation is larger than the difference in spending across hospitals. Higher spending was not associated with a reduction in 30-day mortality or 30-day readmission rates.
Most current health reform policies such as value-based purchasing and 30-day readmission penalties target hospitals as entities, but based on this study there may be a role for more physician-specific reform options. Because they found no significant difference in quality outcomes based on spending, the authors postulate that there may be an opportunity for individual high-spending physicians to decrease their health care utilization without compromising care quality.
The major limitation to this study is that it is a large-scale data analysis and may not capture some of the intricacies of individualized patient care.
Bottom Line: Spending varies across physicians within the same hospital, and is not associated with differences in mortality or readmissions outcomes.
Citation: Tsugawa Y, Jha AK, Newhouse JP, Zaslavsky AM, Jena AB. Variation in Physician Spending and Association With Patient Outcomes. JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.0059.
Dr. Rankin is a hospitalist and director of the family medicine residency inpatient service at the University of New Mexico.
Title: Variation in physician spending not associated with patient outcomes
Clinical Question: Is there a variation in spending between physicians in the same hospital, and does it have an effect on patient outcomes?
Background: Not much is known about the presence of variations in individual physician spending within the same hospital and it is not known if higher-spending physicians have better patient outcomes compared to peers within the same institution.
Setting: National sample of hospitalized Medicare beneficiaries.
Synopsis: Using National Medicare data over a 4-year period, the authors showed that there is wide variation in Part B spending across physicians (hospitalists and general internists) within the same acute care hospital. This inter-physician variation is larger than the difference in spending across hospitals. Higher spending was not associated with a reduction in 30-day mortality or 30-day readmission rates.
Most current health reform policies such as value-based purchasing and 30-day readmission penalties target hospitals as entities, but based on this study there may be a role for more physician-specific reform options. Because they found no significant difference in quality outcomes based on spending, the authors postulate that there may be an opportunity for individual high-spending physicians to decrease their health care utilization without compromising care quality.
The major limitation to this study is that it is a large-scale data analysis and may not capture some of the intricacies of individualized patient care.
Bottom Line: Spending varies across physicians within the same hospital, and is not associated with differences in mortality or readmissions outcomes.
Citation: Tsugawa Y, Jha AK, Newhouse JP, Zaslavsky AM, Jena AB. Variation in Physician Spending and Association With Patient Outcomes. JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.0059.
Dr. Rankin is a hospitalist and director of the family medicine residency inpatient service at the University of New Mexico.
Title: Variation in physician spending not associated with patient outcomes
Clinical Question: Is there a variation in spending between physicians in the same hospital, and does it have an effect on patient outcomes?
Background: Not much is known about the presence of variations in individual physician spending within the same hospital and it is not known if higher-spending physicians have better patient outcomes compared to peers within the same institution.
Setting: National sample of hospitalized Medicare beneficiaries.
Synopsis: Using National Medicare data over a 4-year period, the authors showed that there is wide variation in Part B spending across physicians (hospitalists and general internists) within the same acute care hospital. This inter-physician variation is larger than the difference in spending across hospitals. Higher spending was not associated with a reduction in 30-day mortality or 30-day readmission rates.
Most current health reform policies such as value-based purchasing and 30-day readmission penalties target hospitals as entities, but based on this study there may be a role for more physician-specific reform options. Because they found no significant difference in quality outcomes based on spending, the authors postulate that there may be an opportunity for individual high-spending physicians to decrease their health care utilization without compromising care quality.
The major limitation to this study is that it is a large-scale data analysis and may not capture some of the intricacies of individualized patient care.
Bottom Line: Spending varies across physicians within the same hospital, and is not associated with differences in mortality or readmissions outcomes.
Citation: Tsugawa Y, Jha AK, Newhouse JP, Zaslavsky AM, Jena AB. Variation in Physician Spending and Association With Patient Outcomes. JAMA Intern Med. 2017. doi: 10.1001/jamainternmed.2017.0059.
Dr. Rankin is a hospitalist and director of the family medicine residency inpatient service at the University of New Mexico.
CHMP recommends midostaurin for FLT3+ AML, SM
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending approval for midostaurin (Rydapt®) as a treatment for acute myeloid leukemia (AML) and systemic mastocytosis (SM).
If approved by the European Commission, midostaurin would be used in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation—followed by midostaurin maintenance for patients in complete response—in adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3-mutation-positive.
Midostaurin would also be approved to treat adults with aggressive SM, SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
If approved, midostaurin would be the first targeted treatment available in the European Union for newly diagnosed FLT3+ AML patients and advanced SM patients.
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 2 to 3 months’ of the CHMP’s recommendation. The decision will be applicable to all member states of the European Union, plus Iceland, Liechtenstein, and Norway.
Midostaurin in AML
The CHMP’s recommendation for midostaurin in AML is based on results from the phase 3 RATIFY trial, which were recently published in NEJM.
In RATIFY, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in 717 adults younger than age 60 who had FLT3-mutated AML.
The median overall survival was significantly longer in the midostaurin arm than the placebo arm—74.7 months and 25.6 months, respectively (hazard ratio=0.77, P=0.016).
And the median event-free survival was significantly longer in the midostaurin arm than the placebo arm—8.2 months and 3.0 months, respectively (hazard ratio=0.78, P=0.004).
The most frequent adverse events (AEs) in the midostaurin arm (occurring in at least 20% of patients) were febrile neutropenia, nausea, vomiting, mucositis, headache, musculoskeletal pain, petechiae, device-related infection, epistaxis, hyperglycemia, and upper respiratory tract infections.
The most frequent grade 3/4 AEs (occurring in at least 10% of patients) were febrile neutropenia, device-related infection, and mucositis. Nine percent of patients in the midostaurin arm stopped treatment due to AEs, as did 6% in the placebo arm.
Midostaurin in advanced SM
The CHMP’s recommendation for midostaurin in advanced SM was based on results from a pair of phase 2, single-arm studies, hereafter referred to as Study 2 and Study 3.
Data from Study 2 were published in NEJM in June 2016, and data from Study 3 were presented at the 2010 ASH Annual Meeting.
Study 2 included 116 patients, 115 of whom were evaluable for response.
The overall response rate (ORR) was 17% in the entire cohort, 31% among patients with ASM, 11% among patients with SM-AHN, and 19% among patients with MCL. The complete response rates were 2%, 6%, 0%, and 5%, respectively.
Study 3 included 26 patients with advanced SM. In 3 of the patients, the subtype of SM was unconfirmed.
Among the 17 patients with SM-AHN, there were 10 responses (ORR=59%), including 1 partial response and 9 major responses. In the 6 patients with MCL, there were 2 responses (ORR=33%), which included 1 partial response and 1 major response.
In both studies combined, there were 142 adults with ASM, SM-AHN, or MCL.
The most frequent AEs (excluding laboratory abnormalities) that occurred in at least 20% of these patients were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea.
The most frequent grade 3 or higher AEs (excluding laboratory abnormalities) that occurred in at least 5% of patients were fatigue, sepsis, gastrointestinal hemorrhage, pneumonia, diarrhea, febrile neutropenia, edema, dyspnea, nausea, vomiting, abdominal pain, and renal insufficiency.
Serious AEs occurred in 68% of patients, most commonly infections and gastrointestinal disorders. Twenty-one percent of patients discontinued treatment due to AEs, the most frequent of which were infection, nausea or vomiting, QT prolongation, and gastrointestinal hemorrhage.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending approval for midostaurin (Rydapt®) as a treatment for acute myeloid leukemia (AML) and systemic mastocytosis (SM).
If approved by the European Commission, midostaurin would be used in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation—followed by midostaurin maintenance for patients in complete response—in adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3-mutation-positive.
Midostaurin would also be approved to treat adults with aggressive SM, SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
If approved, midostaurin would be the first targeted treatment available in the European Union for newly diagnosed FLT3+ AML patients and advanced SM patients.
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 2 to 3 months’ of the CHMP’s recommendation. The decision will be applicable to all member states of the European Union, plus Iceland, Liechtenstein, and Norway.
Midostaurin in AML
The CHMP’s recommendation for midostaurin in AML is based on results from the phase 3 RATIFY trial, which were recently published in NEJM.
In RATIFY, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in 717 adults younger than age 60 who had FLT3-mutated AML.
The median overall survival was significantly longer in the midostaurin arm than the placebo arm—74.7 months and 25.6 months, respectively (hazard ratio=0.77, P=0.016).
And the median event-free survival was significantly longer in the midostaurin arm than the placebo arm—8.2 months and 3.0 months, respectively (hazard ratio=0.78, P=0.004).
The most frequent adverse events (AEs) in the midostaurin arm (occurring in at least 20% of patients) were febrile neutropenia, nausea, vomiting, mucositis, headache, musculoskeletal pain, petechiae, device-related infection, epistaxis, hyperglycemia, and upper respiratory tract infections.
The most frequent grade 3/4 AEs (occurring in at least 10% of patients) were febrile neutropenia, device-related infection, and mucositis. Nine percent of patients in the midostaurin arm stopped treatment due to AEs, as did 6% in the placebo arm.
Midostaurin in advanced SM
The CHMP’s recommendation for midostaurin in advanced SM was based on results from a pair of phase 2, single-arm studies, hereafter referred to as Study 2 and Study 3.
Data from Study 2 were published in NEJM in June 2016, and data from Study 3 were presented at the 2010 ASH Annual Meeting.
Study 2 included 116 patients, 115 of whom were evaluable for response.
The overall response rate (ORR) was 17% in the entire cohort, 31% among patients with ASM, 11% among patients with SM-AHN, and 19% among patients with MCL. The complete response rates were 2%, 6%, 0%, and 5%, respectively.
Study 3 included 26 patients with advanced SM. In 3 of the patients, the subtype of SM was unconfirmed.
Among the 17 patients with SM-AHN, there were 10 responses (ORR=59%), including 1 partial response and 9 major responses. In the 6 patients with MCL, there were 2 responses (ORR=33%), which included 1 partial response and 1 major response.
In both studies combined, there were 142 adults with ASM, SM-AHN, or MCL.
The most frequent AEs (excluding laboratory abnormalities) that occurred in at least 20% of these patients were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea.
The most frequent grade 3 or higher AEs (excluding laboratory abnormalities) that occurred in at least 5% of patients were fatigue, sepsis, gastrointestinal hemorrhage, pneumonia, diarrhea, febrile neutropenia, edema, dyspnea, nausea, vomiting, abdominal pain, and renal insufficiency.
Serious AEs occurred in 68% of patients, most commonly infections and gastrointestinal disorders. Twenty-one percent of patients discontinued treatment due to AEs, the most frequent of which were infection, nausea or vomiting, QT prolongation, and gastrointestinal hemorrhage.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending approval for midostaurin (Rydapt®) as a treatment for acute myeloid leukemia (AML) and systemic mastocytosis (SM).
If approved by the European Commission, midostaurin would be used in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation—followed by midostaurin maintenance for patients in complete response—in adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3-mutation-positive.
Midostaurin would also be approved to treat adults with aggressive SM, SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
If approved, midostaurin would be the first targeted treatment available in the European Union for newly diagnosed FLT3+ AML patients and advanced SM patients.
The European Commission typically adheres to the CHMP’s recommendations and delivers its final decision within 2 to 3 months’ of the CHMP’s recommendation. The decision will be applicable to all member states of the European Union, plus Iceland, Liechtenstein, and Norway.
Midostaurin in AML
The CHMP’s recommendation for midostaurin in AML is based on results from the phase 3 RATIFY trial, which were recently published in NEJM.
In RATIFY, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in 717 adults younger than age 60 who had FLT3-mutated AML.
The median overall survival was significantly longer in the midostaurin arm than the placebo arm—74.7 months and 25.6 months, respectively (hazard ratio=0.77, P=0.016).
And the median event-free survival was significantly longer in the midostaurin arm than the placebo arm—8.2 months and 3.0 months, respectively (hazard ratio=0.78, P=0.004).
The most frequent adverse events (AEs) in the midostaurin arm (occurring in at least 20% of patients) were febrile neutropenia, nausea, vomiting, mucositis, headache, musculoskeletal pain, petechiae, device-related infection, epistaxis, hyperglycemia, and upper respiratory tract infections.
The most frequent grade 3/4 AEs (occurring in at least 10% of patients) were febrile neutropenia, device-related infection, and mucositis. Nine percent of patients in the midostaurin arm stopped treatment due to AEs, as did 6% in the placebo arm.
Midostaurin in advanced SM
The CHMP’s recommendation for midostaurin in advanced SM was based on results from a pair of phase 2, single-arm studies, hereafter referred to as Study 2 and Study 3.
Data from Study 2 were published in NEJM in June 2016, and data from Study 3 were presented at the 2010 ASH Annual Meeting.
Study 2 included 116 patients, 115 of whom were evaluable for response.
The overall response rate (ORR) was 17% in the entire cohort, 31% among patients with ASM, 11% among patients with SM-AHN, and 19% among patients with MCL. The complete response rates were 2%, 6%, 0%, and 5%, respectively.
Study 3 included 26 patients with advanced SM. In 3 of the patients, the subtype of SM was unconfirmed.
Among the 17 patients with SM-AHN, there were 10 responses (ORR=59%), including 1 partial response and 9 major responses. In the 6 patients with MCL, there were 2 responses (ORR=33%), which included 1 partial response and 1 major response.
In both studies combined, there were 142 adults with ASM, SM-AHN, or MCL.
The most frequent AEs (excluding laboratory abnormalities) that occurred in at least 20% of these patients were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea.
The most frequent grade 3 or higher AEs (excluding laboratory abnormalities) that occurred in at least 5% of patients were fatigue, sepsis, gastrointestinal hemorrhage, pneumonia, diarrhea, febrile neutropenia, edema, dyspnea, nausea, vomiting, abdominal pain, and renal insufficiency.
Serious AEs occurred in 68% of patients, most commonly infections and gastrointestinal disorders. Twenty-one percent of patients discontinued treatment due to AEs, the most frequent of which were infection, nausea or vomiting, QT prolongation, and gastrointestinal hemorrhage.