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Wearing lateral wedge insoles reduces osteoarthritis knee pain
LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.
An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).
The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.
“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.
There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.
“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.
For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.
All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.
Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m2 who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.
Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.
At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.
Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.
There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).
“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.
“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.
The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.
The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.
SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.
LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.
An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).
The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.
“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.
There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.
“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.
For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.
All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.
Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m2 who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.
Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.
At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.
Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.
There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).
“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.
“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.
The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.
The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.
SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.
LIVERPOOL, ENGLAND – Lateral wedge insoles reduced osteoarthritis knee pain to a greater extent than did wearing neutral insoles in a randomized, controlled, crossover trial.
An overall significant treatment difference of 0.7 points on a 0-10 numerical rating scale global pain score was observed when patients with painful medial osteoarthritis (OA) wore lateral wedge insoles compared with when they wore neutral insoles in their own shoes (95% confidence interval [CI], 0.1-1.2 points; P = .02).
The study’s findings are in contrast to previous research that has found no benefit of lateral wedge insoles in patients with medial compartment knee OA (JAMA. 2013;310[7]:722-30) because patients were specifically prescreened to find those who would be biomechanical responders, David T. Felson, MD, said at the World Congress on Osteoarthritis.
“There is increased medial load in medial knee OA, and that is thought to cause pain and medial joint damage,” Dr. Felson, of Boston University, said at the congress, sponsored by the Osteoarthritis Research Society International.
There is evidence, however, that by moving the center of pressure laterally during walking with the use of lateral wedge insoles, the external knee adduction movement (KAM) can be reduced by around 5%-6%, which in turn can reduce the load across the medial component.
“We asked the following question: ‘If patients were screened to remove those with painful patellofemoral OA and those who did not show a biomechanical response to lateral wedge insoles, would lateral wedge insoles actually reduce pain?’ ” Dr. Felson noted.
For inclusion in the trial, patients needed to be aged between 40 and 80 years and have x-rays showing Kellgren-Lawrence grade 2-4 OA with definite medial and no lateral joint space narrowing in the last 2 years. They then also needed to have experienced knee pain that was rated at least 4 or more on a 0-10 numerical rating scale in the last week. Patients then had to be examined by an experienced physiotherapist or have x-rays to exclude patellofemoral OA and inflammatory arthritis.
All patients then underwent biomechanical assessment which consisted of motion analysis screening. Patients who did not show at least a 2% decrease in KAM after wearing the lateral wedge insoles versus the neutral insoles were excluded.
Of 112 subjects who were screened for the study, there remained 62 with a mean age of 64 years and body mass index of 28 kg/m2 who could be randomized. The subjects, 73% of whom were male, were randomized to first wear either neutral insoles or insoles with a lateral five-degree wedge for 8 weeks and then, after an 8-week washout period, to wear the other type of insole for a further 8 weeks. Participants wore the insoles for at least 4 hours a day and for a median of 7 hours per day.
Results showed that the lateral wedge insoles reduced KAM by 7.5% versus their own shoes and by 6.6% versus a neutral insole, and of the 62 patients randomized, 56 completed the trial. Two patients in each group stopped participating in the trial because of adverse events, which with lateral wedge insoles were cramps in the calf and foot and increased pain in the knee, and with the neutral insoles included a blister and increased pain in knee and foot.
At baseline, the mean global knee pain score in the last week was 5.46. After use of the lateral wedge or neutral insoles, this fell to a respective 4.2 and 4.9.
Patients were asked to report on the pain experience during a nominated activity. The baseline value for pain was 6.18, which decreased to 4.9 and 5.8 in the two groups, respectively, with an overall treatment difference of 0.9 (P = .001) favoring the use of the lateral wedge insoles.
There was improvement in knee pain assessed by the Knee injury and Osteoarthritis Outcomes Score from a baseline of 55 points to a score of 60.6 for lateral wedge and 58.9 for the neutral insoles, a between group difference of –1.7 (P = .45).
“Lateral wedge insoles reduce knee pain in selected subjects with painful medial OA, those without patellofemoral OA, and those who are biomechanical responders to these insoles,” Dr. Felson said.
“I think the importance of this study is that it opens the door to a treatment that we were frustrated wasn’t working,” Dr. Felson said. Insoles are inexpensive, safe, and potentially widely useful, and the research paves the way for further study of these insoles and for perhaps for shoes that could modify knee loads.
The findings open the door to “stratified approaches to knee OA that may also offer us an avenue toward success in developing treatments,” he added.
The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.
SOURCE: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.
REPORTING FROM OARSI 2018
Key clinical point:
Major finding: There was a mean treatment difference of 0.7 points in a global pain score favoring lateral wedge over neutral insoles (P = .02).
Study details: Randomized, controlled, crossover study of 62 patients with painful medial knee OA.
Disclosures: The National Institute for Health Research, Arthritis Research U.K., and the National Institutes of Health sponsored the study. Dr. Felson had no disclosures.
Source: Felson D et al. Osteoarthritis Cartilage. 2018:26(1):S17. Abstract 14.
Hep B therapy: Indefinite or FINITE for e-negative patients?
LAS VEGAS – Current guidelines recommend indefinite continuation of antiviral therapy in chronic hepatitis B patients who are hepatitis B e-antigen (HBeAg)-negative. But emerging data suggest that this may not always be the case.
“It’s very provocative data, though not at the guideline level,” W. Ray Kim, MD, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are patients who really have begged to go off treatment because they are sick of taking the medication for year after year after year,” said Dr. Kim, professor of medicine, gastroenterology and hepatology, Stanford (Calif.) University.
In light of new data, taking them off medication might be “something to consider” in noncirrhotic patients if they are completely suppressed, have normal ALT, and have a low level of quantitative hepatitis B surface antigen (HBsAg), Dr. Kim told attendees.
The most current Association for the Advancement of the Study of Liver Diseases guidelines state that unless there is a competing rationale, antiviral therapy should be continued indefinitely for noncirrhotic adults with HBeAg‐negative immune‐active chronic hepatitis B.
They do also say that treatment discontinuation “may be considered” for individuals with proven loss of HBsAg. “However, there is currently insufficient evidence to definitively guide treatment decisions for such persons,” the guidelines say.
Evidence has emerged since those guideline statements were written. Most recently, German investigators published results of the FINITE study showing some long-term responses after stopping tenofovir disoproxil fumarate (TDF) in noncirrhotic, HBeAg-negative patients.
In that prospective, controlled study, 62% of patients who stopped TDF therapy (n = 13) stayed off therapy to week 144 of treatment follow-up. Four of the patients achieved HBsAg loss, and median HBsAg change was –0.59log10IU/mL vs. 0.21log10IU/mL in patients who stayed on TDF therapy.
Investigators said that result demonstrated the potential of stopping long-term TDF treatment and seeing either HBsAg loss or sustained virologic response.
Before that, a retrospective study from investigators in Taiwan showed that age plus level of HBsAg were associated with HBV relapse after entecavir treatment in HBeAg-negative patients. According to investigators, those results suggested HBsAg levels could be used to guide timing of entecavir cessation.
If antiviral therapy is stopped in an HBeAg-negative patient, that patient should be monitored every 3 month for a year for recurrent viremia, ALT flares, and hepatic decompensation, Dr. Kim said at the meeting.
Even before stopping, “there are a number of factors to consider, including biological relapse, flare, hepatic decompensation,” he said.
On the other hand, there is the burden of continued therapy, financial concerns of continuing treatment due not only to medication costs but also long-term monitoring, as well as patient and provider preference, he noted in his presentation.
Global Academy and this news organization are owned by the same parent company.
Dr. Kim reported serving as a consultant to Gilead.
LAS VEGAS – Current guidelines recommend indefinite continuation of antiviral therapy in chronic hepatitis B patients who are hepatitis B e-antigen (HBeAg)-negative. But emerging data suggest that this may not always be the case.
“It’s very provocative data, though not at the guideline level,” W. Ray Kim, MD, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are patients who really have begged to go off treatment because they are sick of taking the medication for year after year after year,” said Dr. Kim, professor of medicine, gastroenterology and hepatology, Stanford (Calif.) University.
In light of new data, taking them off medication might be “something to consider” in noncirrhotic patients if they are completely suppressed, have normal ALT, and have a low level of quantitative hepatitis B surface antigen (HBsAg), Dr. Kim told attendees.
The most current Association for the Advancement of the Study of Liver Diseases guidelines state that unless there is a competing rationale, antiviral therapy should be continued indefinitely for noncirrhotic adults with HBeAg‐negative immune‐active chronic hepatitis B.
They do also say that treatment discontinuation “may be considered” for individuals with proven loss of HBsAg. “However, there is currently insufficient evidence to definitively guide treatment decisions for such persons,” the guidelines say.
Evidence has emerged since those guideline statements were written. Most recently, German investigators published results of the FINITE study showing some long-term responses after stopping tenofovir disoproxil fumarate (TDF) in noncirrhotic, HBeAg-negative patients.
In that prospective, controlled study, 62% of patients who stopped TDF therapy (n = 13) stayed off therapy to week 144 of treatment follow-up. Four of the patients achieved HBsAg loss, and median HBsAg change was –0.59log10IU/mL vs. 0.21log10IU/mL in patients who stayed on TDF therapy.
Investigators said that result demonstrated the potential of stopping long-term TDF treatment and seeing either HBsAg loss or sustained virologic response.
Before that, a retrospective study from investigators in Taiwan showed that age plus level of HBsAg were associated with HBV relapse after entecavir treatment in HBeAg-negative patients. According to investigators, those results suggested HBsAg levels could be used to guide timing of entecavir cessation.
If antiviral therapy is stopped in an HBeAg-negative patient, that patient should be monitored every 3 month for a year for recurrent viremia, ALT flares, and hepatic decompensation, Dr. Kim said at the meeting.
Even before stopping, “there are a number of factors to consider, including biological relapse, flare, hepatic decompensation,” he said.
On the other hand, there is the burden of continued therapy, financial concerns of continuing treatment due not only to medication costs but also long-term monitoring, as well as patient and provider preference, he noted in his presentation.
Global Academy and this news organization are owned by the same parent company.
Dr. Kim reported serving as a consultant to Gilead.
LAS VEGAS – Current guidelines recommend indefinite continuation of antiviral therapy in chronic hepatitis B patients who are hepatitis B e-antigen (HBeAg)-negative. But emerging data suggest that this may not always be the case.
“It’s very provocative data, though not at the guideline level,” W. Ray Kim, MD, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are patients who really have begged to go off treatment because they are sick of taking the medication for year after year after year,” said Dr. Kim, professor of medicine, gastroenterology and hepatology, Stanford (Calif.) University.
In light of new data, taking them off medication might be “something to consider” in noncirrhotic patients if they are completely suppressed, have normal ALT, and have a low level of quantitative hepatitis B surface antigen (HBsAg), Dr. Kim told attendees.
The most current Association for the Advancement of the Study of Liver Diseases guidelines state that unless there is a competing rationale, antiviral therapy should be continued indefinitely for noncirrhotic adults with HBeAg‐negative immune‐active chronic hepatitis B.
They do also say that treatment discontinuation “may be considered” for individuals with proven loss of HBsAg. “However, there is currently insufficient evidence to definitively guide treatment decisions for such persons,” the guidelines say.
Evidence has emerged since those guideline statements were written. Most recently, German investigators published results of the FINITE study showing some long-term responses after stopping tenofovir disoproxil fumarate (TDF) in noncirrhotic, HBeAg-negative patients.
In that prospective, controlled study, 62% of patients who stopped TDF therapy (n = 13) stayed off therapy to week 144 of treatment follow-up. Four of the patients achieved HBsAg loss, and median HBsAg change was –0.59log10IU/mL vs. 0.21log10IU/mL in patients who stayed on TDF therapy.
Investigators said that result demonstrated the potential of stopping long-term TDF treatment and seeing either HBsAg loss or sustained virologic response.
Before that, a retrospective study from investigators in Taiwan showed that age plus level of HBsAg were associated with HBV relapse after entecavir treatment in HBeAg-negative patients. According to investigators, those results suggested HBsAg levels could be used to guide timing of entecavir cessation.
If antiviral therapy is stopped in an HBeAg-negative patient, that patient should be monitored every 3 month for a year for recurrent viremia, ALT flares, and hepatic decompensation, Dr. Kim said at the meeting.
Even before stopping, “there are a number of factors to consider, including biological relapse, flare, hepatic decompensation,” he said.
On the other hand, there is the burden of continued therapy, financial concerns of continuing treatment due not only to medication costs but also long-term monitoring, as well as patient and provider preference, he noted in his presentation.
Global Academy and this news organization are owned by the same parent company.
Dr. Kim reported serving as a consultant to Gilead.
EXPERT ANALYSIS FROM PERSPECTIVES IN DIGESTIVE DISEASES
Merkel Cell Carcinoma: Presentation, Pathogenesis, and Spontaneous Regression
Cathepsin K inhibitor exhibits bone protecting effects in osteoarthritis
LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
REPORTING FROM OARSI 2018
Key clinical point:
Major finding: A 63%-66% reduction in the medial femur bone area was observed with MIV-711, compared with placebo.
Study details: Randomized, double-blind, placebo-controlled phase 2a study of 240 patients with osteoarthritis knee pain.
Disclosures: The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speakers bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
Source: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
VIDEO: Postpartum care gets a new look
AUSTIN, TEX. – While women may have a plethora of options for care during pregnancy, attention given to women after birth is seriously lacking, with detrimental effect.
Currently, postpartum care is limited to a follow-up appointment 6 weeks after pregnancy, but according to Alison Stuebe, MD, medical director of lactation services at the University of North Carolina, Chapel Hill, there is too much going on in those 6 weeks to continue this model.
To address preferred changes to this system of care, the .
“What we’d like to do with the new committee opinion is move from this one-off visit at 6 weeks where we tell people ‘you’re good to go, you can have sex, get out of my office,’ to a much more comprehensive approach that reaches out to moms in the first couple of weeks,” explained Dr. Stuebe. “Whether that’s by phone, by asynchronous communication, by in-person visit, [the physician] finds out what’s going on, and then makes appropriate recommendations to help her rather than waiting to see what’s left after 6 weeks,” she said at ACOG’s annual clinical and scientific meeting.
Paying for these services is a big barrier right now, said Dr. Stuebe, but some solutions have already shown signs of being cost effective.
One example, in Dr. Stuebe’s hometown of Durham County, N.C., is a program called Durham Connect, which puts nurses in contact with women at 3 weeks postpartum to make assessments of what care the mother needs, and then offers service referrals to help with those needs.
According to Dr. Stuebe, studies have found every dollar invested in the program would save $3 in emergency department visits for children.
As postpartum care evolves, the most important thing is to remember that when it comes to pregnancy and birth, just because the baby is out doesn’t mean the mother can be ignored, she said.
“When we think about the way postpartum care exists today, you think about the mom being the candy wrapper and the baby being the candy; when the candy’s out of the wrapper, we toss the wrapper,” said Dr. Stuebe. “What these new guidelines are saying is this wrapper is actually pretty important.”
The revised committee opinion states: “The comprehensive postpartum visit should include a full assessment of physical, social, and psychological well-being, including the following domains: mood and emotional well-being; infant care and feeding; sexuality, contraception, and birth spacing; sleep and fatigue; physical recovery from birth; chronic disease management; and health maintenance.”
Dr. Stuebe receives support from Janssen.
AUSTIN, TEX. – While women may have a plethora of options for care during pregnancy, attention given to women after birth is seriously lacking, with detrimental effect.
Currently, postpartum care is limited to a follow-up appointment 6 weeks after pregnancy, but according to Alison Stuebe, MD, medical director of lactation services at the University of North Carolina, Chapel Hill, there is too much going on in those 6 weeks to continue this model.
To address preferred changes to this system of care, the .
“What we’d like to do with the new committee opinion is move from this one-off visit at 6 weeks where we tell people ‘you’re good to go, you can have sex, get out of my office,’ to a much more comprehensive approach that reaches out to moms in the first couple of weeks,” explained Dr. Stuebe. “Whether that’s by phone, by asynchronous communication, by in-person visit, [the physician] finds out what’s going on, and then makes appropriate recommendations to help her rather than waiting to see what’s left after 6 weeks,” she said at ACOG’s annual clinical and scientific meeting.
Paying for these services is a big barrier right now, said Dr. Stuebe, but some solutions have already shown signs of being cost effective.
One example, in Dr. Stuebe’s hometown of Durham County, N.C., is a program called Durham Connect, which puts nurses in contact with women at 3 weeks postpartum to make assessments of what care the mother needs, and then offers service referrals to help with those needs.
According to Dr. Stuebe, studies have found every dollar invested in the program would save $3 in emergency department visits for children.
As postpartum care evolves, the most important thing is to remember that when it comes to pregnancy and birth, just because the baby is out doesn’t mean the mother can be ignored, she said.
“When we think about the way postpartum care exists today, you think about the mom being the candy wrapper and the baby being the candy; when the candy’s out of the wrapper, we toss the wrapper,” said Dr. Stuebe. “What these new guidelines are saying is this wrapper is actually pretty important.”
The revised committee opinion states: “The comprehensive postpartum visit should include a full assessment of physical, social, and psychological well-being, including the following domains: mood and emotional well-being; infant care and feeding; sexuality, contraception, and birth spacing; sleep and fatigue; physical recovery from birth; chronic disease management; and health maintenance.”
Dr. Stuebe receives support from Janssen.
AUSTIN, TEX. – While women may have a plethora of options for care during pregnancy, attention given to women after birth is seriously lacking, with detrimental effect.
Currently, postpartum care is limited to a follow-up appointment 6 weeks after pregnancy, but according to Alison Stuebe, MD, medical director of lactation services at the University of North Carolina, Chapel Hill, there is too much going on in those 6 weeks to continue this model.
To address preferred changes to this system of care, the .
“What we’d like to do with the new committee opinion is move from this one-off visit at 6 weeks where we tell people ‘you’re good to go, you can have sex, get out of my office,’ to a much more comprehensive approach that reaches out to moms in the first couple of weeks,” explained Dr. Stuebe. “Whether that’s by phone, by asynchronous communication, by in-person visit, [the physician] finds out what’s going on, and then makes appropriate recommendations to help her rather than waiting to see what’s left after 6 weeks,” she said at ACOG’s annual clinical and scientific meeting.
Paying for these services is a big barrier right now, said Dr. Stuebe, but some solutions have already shown signs of being cost effective.
One example, in Dr. Stuebe’s hometown of Durham County, N.C., is a program called Durham Connect, which puts nurses in contact with women at 3 weeks postpartum to make assessments of what care the mother needs, and then offers service referrals to help with those needs.
According to Dr. Stuebe, studies have found every dollar invested in the program would save $3 in emergency department visits for children.
As postpartum care evolves, the most important thing is to remember that when it comes to pregnancy and birth, just because the baby is out doesn’t mean the mother can be ignored, she said.
“When we think about the way postpartum care exists today, you think about the mom being the candy wrapper and the baby being the candy; when the candy’s out of the wrapper, we toss the wrapper,” said Dr. Stuebe. “What these new guidelines are saying is this wrapper is actually pretty important.”
The revised committee opinion states: “The comprehensive postpartum visit should include a full assessment of physical, social, and psychological well-being, including the following domains: mood and emotional well-being; infant care and feeding; sexuality, contraception, and birth spacing; sleep and fatigue; physical recovery from birth; chronic disease management; and health maintenance.”
Dr. Stuebe receives support from Janssen.
REPORTING FROM ACOG 2018
Prompt palliative care cut hospital costs in pooled study
For adults with serious illness, consulting with a palliative care team within 3 days of hospital admission significantly reduced hospital costs, according to findings from a systematic review and meta-analysis.
In a pooled analysis of six cohort studies, average cost savings per admission were $3,237 (95% confidence interval, –$3,581 to −$2,893) overall, $4,251 for patients with cancer, and $2,105 for patients with other serious illnesses (all P values less than .001), reported Peter May, PhD, of Trinity College Dublin, and his associates.
In this latter group, prompt palliative care consultations saved more when patients had at least four comorbidities rather than two or fewer comorbidities, the reviewers wrote. The report was published in JAMA Internal Medicine.
About one in four Medicare beneficiaries dies in acute care hospitals, often after weeks of intensive, costly care that may not reflect personal wishes, according to an earlier study (JAMA. 2013;309:470-7). Economic studies have tried to pinpoint the cost savings of palliative care. These studies have found it important to consider both the clinical characteristics of patients and the amount of time between admission and palliative consultations, the reviewers noted. However, heterogeneity among older studies had precluded pooled analyses.
The six studies in this meta-analysis were identified by a search of Embase, PsycINFO, CENTRAL, PubMed, CINAHL, and EconLit databases for economic studies of hospital-based palliative care consultations. The studies were published between 2008 and 2017 and included 133,118 adults with cancer, chronic obstructive pulmonary disease, major organ failure, AIDS/HIV, or serious neurodegenerative disease. Patients tended to be in their 60s and were usually Medicare beneficiaries, although one study focused only on Medicaid enrollees. Forty-one percent of patients had a primary diagnosis of cancer, and 93% were discharged alive. Most also had at least two comorbidities. Only 3.6% received a palliative care consultation (range, 2.2% to 22.3%).
The link that they found between more comorbidities and greater cost savings “is the reverse of prior research that assumed that long-stay, high-cost hospitalized patients could not have their care trajectories affected by palliative care,” the researchers wrote. “Current palliative care provision in the United States is characterized by widespread understaffing. Our results suggest that acute care hospitals may be able to reduce costs for this population by increasing palliative care capacity to meet national guidelines.”
Dr. May received grant support from The Atlantic Philanthropies. The reviewers reported having no conflicts of interest.
SOURCE: May P et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.0750.
For adults with serious illness, consulting with a palliative care team within 3 days of hospital admission significantly reduced hospital costs, according to findings from a systematic review and meta-analysis.
In a pooled analysis of six cohort studies, average cost savings per admission were $3,237 (95% confidence interval, –$3,581 to −$2,893) overall, $4,251 for patients with cancer, and $2,105 for patients with other serious illnesses (all P values less than .001), reported Peter May, PhD, of Trinity College Dublin, and his associates.
In this latter group, prompt palliative care consultations saved more when patients had at least four comorbidities rather than two or fewer comorbidities, the reviewers wrote. The report was published in JAMA Internal Medicine.
About one in four Medicare beneficiaries dies in acute care hospitals, often after weeks of intensive, costly care that may not reflect personal wishes, according to an earlier study (JAMA. 2013;309:470-7). Economic studies have tried to pinpoint the cost savings of palliative care. These studies have found it important to consider both the clinical characteristics of patients and the amount of time between admission and palliative consultations, the reviewers noted. However, heterogeneity among older studies had precluded pooled analyses.
The six studies in this meta-analysis were identified by a search of Embase, PsycINFO, CENTRAL, PubMed, CINAHL, and EconLit databases for economic studies of hospital-based palliative care consultations. The studies were published between 2008 and 2017 and included 133,118 adults with cancer, chronic obstructive pulmonary disease, major organ failure, AIDS/HIV, or serious neurodegenerative disease. Patients tended to be in their 60s and were usually Medicare beneficiaries, although one study focused only on Medicaid enrollees. Forty-one percent of patients had a primary diagnosis of cancer, and 93% were discharged alive. Most also had at least two comorbidities. Only 3.6% received a palliative care consultation (range, 2.2% to 22.3%).
The link that they found between more comorbidities and greater cost savings “is the reverse of prior research that assumed that long-stay, high-cost hospitalized patients could not have their care trajectories affected by palliative care,” the researchers wrote. “Current palliative care provision in the United States is characterized by widespread understaffing. Our results suggest that acute care hospitals may be able to reduce costs for this population by increasing palliative care capacity to meet national guidelines.”
Dr. May received grant support from The Atlantic Philanthropies. The reviewers reported having no conflicts of interest.
SOURCE: May P et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.0750.
For adults with serious illness, consulting with a palliative care team within 3 days of hospital admission significantly reduced hospital costs, according to findings from a systematic review and meta-analysis.
In a pooled analysis of six cohort studies, average cost savings per admission were $3,237 (95% confidence interval, –$3,581 to −$2,893) overall, $4,251 for patients with cancer, and $2,105 for patients with other serious illnesses (all P values less than .001), reported Peter May, PhD, of Trinity College Dublin, and his associates.
In this latter group, prompt palliative care consultations saved more when patients had at least four comorbidities rather than two or fewer comorbidities, the reviewers wrote. The report was published in JAMA Internal Medicine.
About one in four Medicare beneficiaries dies in acute care hospitals, often after weeks of intensive, costly care that may not reflect personal wishes, according to an earlier study (JAMA. 2013;309:470-7). Economic studies have tried to pinpoint the cost savings of palliative care. These studies have found it important to consider both the clinical characteristics of patients and the amount of time between admission and palliative consultations, the reviewers noted. However, heterogeneity among older studies had precluded pooled analyses.
The six studies in this meta-analysis were identified by a search of Embase, PsycINFO, CENTRAL, PubMed, CINAHL, and EconLit databases for economic studies of hospital-based palliative care consultations. The studies were published between 2008 and 2017 and included 133,118 adults with cancer, chronic obstructive pulmonary disease, major organ failure, AIDS/HIV, or serious neurodegenerative disease. Patients tended to be in their 60s and were usually Medicare beneficiaries, although one study focused only on Medicaid enrollees. Forty-one percent of patients had a primary diagnosis of cancer, and 93% were discharged alive. Most also had at least two comorbidities. Only 3.6% received a palliative care consultation (range, 2.2% to 22.3%).
The link that they found between more comorbidities and greater cost savings “is the reverse of prior research that assumed that long-stay, high-cost hospitalized patients could not have their care trajectories affected by palliative care,” the researchers wrote. “Current palliative care provision in the United States is characterized by widespread understaffing. Our results suggest that acute care hospitals may be able to reduce costs for this population by increasing palliative care capacity to meet national guidelines.”
Dr. May received grant support from The Atlantic Philanthropies. The reviewers reported having no conflicts of interest.
SOURCE: May P et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.0750.
FROM JAMA INTERNAL MEDICINE
Key clinical point:
Major finding: Average cost savings per admission were $3,237 overall, $4,251 for patients with cancer, and $2,105 for patients with other serious illnesses (all P-values less than .001).
Study details: Systematic review and meta-analysis of six cohort studies of 133,118 adults with cancer, chronic obstructive pulmonary disease, major organ failure, AIDS/HIV, or serious neurodegenerative disease.
Disclosures: Dr. May received grant support from The Atlantic Philanthropies. The reviewers reported having no conflicts of interest.
Source: May P et al. JAMA Intern Med. 2018 Apr 30. doi: 10.1001/jamainternmed.2018.0750.
VRIC is May 9; Register On-Site
Learn about emerging vascular science, engage with researchers, network with colleagues, and support your peers at VRIC, our ‘Annual Meeting’ for basic and translational vascular researchers. Online registration has ended by attendees can register in person the day of the conference. VRIC 2018 will be held at the Hilton San Francisco Union Square, on May 9. Learn more and find the program schedule here.
Learn about emerging vascular science, engage with researchers, network with colleagues, and support your peers at VRIC, our ‘Annual Meeting’ for basic and translational vascular researchers. Online registration has ended by attendees can register in person the day of the conference. VRIC 2018 will be held at the Hilton San Francisco Union Square, on May 9. Learn more and find the program schedule here.
Learn about emerging vascular science, engage with researchers, network with colleagues, and support your peers at VRIC, our ‘Annual Meeting’ for basic and translational vascular researchers. Online registration has ended by attendees can register in person the day of the conference. VRIC 2018 will be held at the Hilton San Francisco Union Square, on May 9. Learn more and find the program schedule here.
Circulating biomarkers predicted melanoma survival
Among patients with metastatic melanoma, detectable circulating levels of BRAFV600 mutated circulating tumor DNA and elevated levels of circulating hepatocyte growth factor separately predicted significantly worse survival, regardless of treatment.
After adjusting for lactate dehydrogenase, ECOG (Eastern Cooperative Oncology Group) status, disease stage, and treatment, hazard ratios for overall survival were 1.75 (95% confidence interval, 1.35-2.28) for detectable versus undetectable circulating tumor DNA (ctDNA) and 1.24 (95% CI, 1.00-1.53) for high versus low circulating hepatocyte growth factor (cHGF), reported William Lu, PhD, of Genentech in South San Francisco, with his associates. Their retrospective, exploratory analysis of the phase 3 BRIM-3 trial was published in JCO Precision Oncology.
BRIM-3 was a multicenter, open-label trial of 675 patients with previously untreated unresectable stage IIIC or stage IV melanoma that tested positive for the BRAFV600 mutation. Patients received either vemurafenib or dacarbazine therapy.
Baseline ctDNA, baseline cHGF, and ECOG performance status most strongly predicted overall survival, said the investigators. Patients whose mutant ctDNA fraction exceeded 0.039 had an 11.5-month shorter median overall survival on vemurafenib (P less than .001) and a 13.9-month shorter median overall survival on dacarbazine (P less than .001) than patients whose mutant ctDNA fraction was less than 0.039, they explained. Similarly, median overall survival times were 5.4 months shorter for vemurafenib (P = .002) and 12.3 months shorter for dacarbazine (P less than .001) when patients had high (more than 438 pg/mL) versus low circulating cHGF.
Median overall survival for vemurafenib was shortest (7.3 months) in the subgroup of 64 patients with detectable BRAFV600 ctDNA and elevated cHGF, according to the researchers. In contrast, median overall survival for vemurafenib was longest (22.0 months) when patients had undetectable ctDNA and an ECOG status of 0.
“Although similar studies have been performed, to our knowledge, our study is unique in its size and in its design as a randomized trial,” Dr. Lu and associates concluded. “The biomarkers in this study can be readily acquired and measured, and require only small volumes of plasma.” They suggested validating the findings in a separate dataset.
F. Hoffman-La Roche provided funding. Roche Molecular Systems makes the Cobas 4800 BRAFV600 Mutation Test used in the study. Dr. Lu disclosed employment and research funding from Genentech/Roche.
SOURCE: Lu W et al. JCO Precis Oncol. 2018 Apr 25. doi: 10.1200/PO.17.00168.
Among patients with metastatic melanoma, detectable circulating levels of BRAFV600 mutated circulating tumor DNA and elevated levels of circulating hepatocyte growth factor separately predicted significantly worse survival, regardless of treatment.
After adjusting for lactate dehydrogenase, ECOG (Eastern Cooperative Oncology Group) status, disease stage, and treatment, hazard ratios for overall survival were 1.75 (95% confidence interval, 1.35-2.28) for detectable versus undetectable circulating tumor DNA (ctDNA) and 1.24 (95% CI, 1.00-1.53) for high versus low circulating hepatocyte growth factor (cHGF), reported William Lu, PhD, of Genentech in South San Francisco, with his associates. Their retrospective, exploratory analysis of the phase 3 BRIM-3 trial was published in JCO Precision Oncology.
BRIM-3 was a multicenter, open-label trial of 675 patients with previously untreated unresectable stage IIIC or stage IV melanoma that tested positive for the BRAFV600 mutation. Patients received either vemurafenib or dacarbazine therapy.
Baseline ctDNA, baseline cHGF, and ECOG performance status most strongly predicted overall survival, said the investigators. Patients whose mutant ctDNA fraction exceeded 0.039 had an 11.5-month shorter median overall survival on vemurafenib (P less than .001) and a 13.9-month shorter median overall survival on dacarbazine (P less than .001) than patients whose mutant ctDNA fraction was less than 0.039, they explained. Similarly, median overall survival times were 5.4 months shorter for vemurafenib (P = .002) and 12.3 months shorter for dacarbazine (P less than .001) when patients had high (more than 438 pg/mL) versus low circulating cHGF.
Median overall survival for vemurafenib was shortest (7.3 months) in the subgroup of 64 patients with detectable BRAFV600 ctDNA and elevated cHGF, according to the researchers. In contrast, median overall survival for vemurafenib was longest (22.0 months) when patients had undetectable ctDNA and an ECOG status of 0.
“Although similar studies have been performed, to our knowledge, our study is unique in its size and in its design as a randomized trial,” Dr. Lu and associates concluded. “The biomarkers in this study can be readily acquired and measured, and require only small volumes of plasma.” They suggested validating the findings in a separate dataset.
F. Hoffman-La Roche provided funding. Roche Molecular Systems makes the Cobas 4800 BRAFV600 Mutation Test used in the study. Dr. Lu disclosed employment and research funding from Genentech/Roche.
SOURCE: Lu W et al. JCO Precis Oncol. 2018 Apr 25. doi: 10.1200/PO.17.00168.
Among patients with metastatic melanoma, detectable circulating levels of BRAFV600 mutated circulating tumor DNA and elevated levels of circulating hepatocyte growth factor separately predicted significantly worse survival, regardless of treatment.
After adjusting for lactate dehydrogenase, ECOG (Eastern Cooperative Oncology Group) status, disease stage, and treatment, hazard ratios for overall survival were 1.75 (95% confidence interval, 1.35-2.28) for detectable versus undetectable circulating tumor DNA (ctDNA) and 1.24 (95% CI, 1.00-1.53) for high versus low circulating hepatocyte growth factor (cHGF), reported William Lu, PhD, of Genentech in South San Francisco, with his associates. Their retrospective, exploratory analysis of the phase 3 BRIM-3 trial was published in JCO Precision Oncology.
BRIM-3 was a multicenter, open-label trial of 675 patients with previously untreated unresectable stage IIIC or stage IV melanoma that tested positive for the BRAFV600 mutation. Patients received either vemurafenib or dacarbazine therapy.
Baseline ctDNA, baseline cHGF, and ECOG performance status most strongly predicted overall survival, said the investigators. Patients whose mutant ctDNA fraction exceeded 0.039 had an 11.5-month shorter median overall survival on vemurafenib (P less than .001) and a 13.9-month shorter median overall survival on dacarbazine (P less than .001) than patients whose mutant ctDNA fraction was less than 0.039, they explained. Similarly, median overall survival times were 5.4 months shorter for vemurafenib (P = .002) and 12.3 months shorter for dacarbazine (P less than .001) when patients had high (more than 438 pg/mL) versus low circulating cHGF.
Median overall survival for vemurafenib was shortest (7.3 months) in the subgroup of 64 patients with detectable BRAFV600 ctDNA and elevated cHGF, according to the researchers. In contrast, median overall survival for vemurafenib was longest (22.0 months) when patients had undetectable ctDNA and an ECOG status of 0.
“Although similar studies have been performed, to our knowledge, our study is unique in its size and in its design as a randomized trial,” Dr. Lu and associates concluded. “The biomarkers in this study can be readily acquired and measured, and require only small volumes of plasma.” They suggested validating the findings in a separate dataset.
F. Hoffman-La Roche provided funding. Roche Molecular Systems makes the Cobas 4800 BRAFV600 Mutation Test used in the study. Dr. Lu disclosed employment and research funding from Genentech/Roche.
SOURCE: Lu W et al. JCO Precis Oncol. 2018 Apr 25. doi: 10.1200/PO.17.00168.
FROM JCO PRECISION ONCOLOGY
Key clinical point: Among patients with metastatic melanoma, high circulating levels of BRAFV600 mutated circulating tumor DNA and circulating hepatocyte growth factor predicted significantly worse overall survival, irrespective of treatment.
Major finding: Adjusted hazard ratios for overall survival were 1.75 for high versus undetectable circulating tumor DNA and 1.24 for high versus low circulating hepatocyte growth factor.
Study details: A retrospective, exploratory analysis of 675 patients with metastatic BRAFV600 mutated advanced melanoma.
Disclosures: F. Hoffman-La Roche provided funding. Roche Molecular Systems makes the Cobas 4800 BRAFV600 Mutation Test used in the study. Dr. Lu disclosed employment and research funding from Genentech/Roche.
Source: Lu W et al. JCO Precis Oncol. 2018 Apr 25. doi: 10.1200/PO.17.00168.
MDedge Daily News: Female physicans face enduring wage gap
A metabolic syndrome scoring system predicts cardiovascular disease risk in type 2 diabetes. A national suicide hotline could become a reality. And anticholinergics’ link to dementia calls for vigilance in elderly patients.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
A metabolic syndrome scoring system predicts cardiovascular disease risk in type 2 diabetes. A national suicide hotline could become a reality. And anticholinergics’ link to dementia calls for vigilance in elderly patients.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
A metabolic syndrome scoring system predicts cardiovascular disease risk in type 2 diabetes. A national suicide hotline could become a reality. And anticholinergics’ link to dementia calls for vigilance in elderly patients.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Getting At-Risk Kids to Change Sexual Behavior
In 2015, young people aged 13- 24 years accounted for > 1 in 5 new HIV diagnoses in the US. Young people aged 15-24 years also account for half of all new sexually transmitted disease infections. Many of those high-risk youth are caught in the juvenile justice system, where they experience more mental illness, substance abuse, and STDs than their peers in the general population.
It is a challenge to identify and implement effective prevention strategies for these young people, but a study at the University of Illinois shows potential. PHAT Life: Preventing HIV/AIDS Among Teens uses role-playing, videos, games, and skill-building exercises to promote knowledge about HIV/AIDS, positive coping, and problem-solving skills.
The study was conducted with 310 urban teens, mostly African American boys, on probation in Chicago’s Cook County, the second-largest county justice system in the US. The participants were assigned to PHAT Life or an equally intensive health information program. Both 2-week programs consisted of 8 90- to 120-minute sessions, delivered at detention-alternative after-school programs.
The study measured the degree of condom use and number of sexual partners in the 6 months before and after the intervention. Among participants who reported the highest-risk sexual behavior at baseline, those assigned to PHAT Life were over 4 times more likely than those in the control group to report a reduction in number of sexual partners and more consistent condom use. Of those who reported having had sex before age 12, the PHAT Life participants reported significantly fewer sexual partners after the intervention.
“Uniquely tailored interventions like PHAT Life … are essential to mitigate young offenders’ poor long-term trajectories,” says Geri Donenberg, PhD, study leader.
The next step, the researchers say, is to identify how best to disseminate PHAT Life resources to ensure it’s self-sustaining in the juvenile justice system.
In 2015, young people aged 13- 24 years accounted for > 1 in 5 new HIV diagnoses in the US. Young people aged 15-24 years also account for half of all new sexually transmitted disease infections. Many of those high-risk youth are caught in the juvenile justice system, where they experience more mental illness, substance abuse, and STDs than their peers in the general population.
It is a challenge to identify and implement effective prevention strategies for these young people, but a study at the University of Illinois shows potential. PHAT Life: Preventing HIV/AIDS Among Teens uses role-playing, videos, games, and skill-building exercises to promote knowledge about HIV/AIDS, positive coping, and problem-solving skills.
The study was conducted with 310 urban teens, mostly African American boys, on probation in Chicago’s Cook County, the second-largest county justice system in the US. The participants were assigned to PHAT Life or an equally intensive health information program. Both 2-week programs consisted of 8 90- to 120-minute sessions, delivered at detention-alternative after-school programs.
The study measured the degree of condom use and number of sexual partners in the 6 months before and after the intervention. Among participants who reported the highest-risk sexual behavior at baseline, those assigned to PHAT Life were over 4 times more likely than those in the control group to report a reduction in number of sexual partners and more consistent condom use. Of those who reported having had sex before age 12, the PHAT Life participants reported significantly fewer sexual partners after the intervention.
“Uniquely tailored interventions like PHAT Life … are essential to mitigate young offenders’ poor long-term trajectories,” says Geri Donenberg, PhD, study leader.
The next step, the researchers say, is to identify how best to disseminate PHAT Life resources to ensure it’s self-sustaining in the juvenile justice system.
In 2015, young people aged 13- 24 years accounted for > 1 in 5 new HIV diagnoses in the US. Young people aged 15-24 years also account for half of all new sexually transmitted disease infections. Many of those high-risk youth are caught in the juvenile justice system, where they experience more mental illness, substance abuse, and STDs than their peers in the general population.
It is a challenge to identify and implement effective prevention strategies for these young people, but a study at the University of Illinois shows potential. PHAT Life: Preventing HIV/AIDS Among Teens uses role-playing, videos, games, and skill-building exercises to promote knowledge about HIV/AIDS, positive coping, and problem-solving skills.
The study was conducted with 310 urban teens, mostly African American boys, on probation in Chicago’s Cook County, the second-largest county justice system in the US. The participants were assigned to PHAT Life or an equally intensive health information program. Both 2-week programs consisted of 8 90- to 120-minute sessions, delivered at detention-alternative after-school programs.
The study measured the degree of condom use and number of sexual partners in the 6 months before and after the intervention. Among participants who reported the highest-risk sexual behavior at baseline, those assigned to PHAT Life were over 4 times more likely than those in the control group to report a reduction in number of sexual partners and more consistent condom use. Of those who reported having had sex before age 12, the PHAT Life participants reported significantly fewer sexual partners after the intervention.
“Uniquely tailored interventions like PHAT Life … are essential to mitigate young offenders’ poor long-term trajectories,” says Geri Donenberg, PhD, study leader.
The next step, the researchers say, is to identify how best to disseminate PHAT Life resources to ensure it’s self-sustaining in the juvenile justice system.