ORLANDO – A biomarker algorithm was better than was clinical response at predicting outcomes after 1 week of systemic steroid treatment for graft-versus-host disease, according to findings from a multicenter study.

The findings have implications for early decision making regarding treatment course, Hannah Major-Monfried reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“The same GVHD algorithm that stratifies patients at day 7 after transplant, at [GVHD] diagnosis, also stratifies them after 1 week of steroid treatment into two groups with distinct risks for treatment failure, 6-month nonrelapse mortality, and overall survival,” she said.

The biomarker algorithm, which includes measures of ST2 and REG3-alpha, was previously shown to predict day-28 treatment response and 6-month non-relapse mortality (NRM) when applied at day 7 post transplant before the onset of GVHD and at the time of diagnosis, said Ms. Major-Monfried, a third-year medical student at Icahn School of Medicine at Mount Sinai, New York.

For the current analysis, levels of the biomarkers were measured after 1 week of treatment in 378 patients with acute GVHD from 11 centers in the Mount Sinai Acute GVHD International Consortium.

In a test cohort that included 236 of the patients, the measurements were used to generate a new predicted probability, or treatment score, for 6-month NRM, which had a value between 0 and 1.

Of the 236 patients, 93 (39%) were considered to have high posttreatment probability of NRM, and the remaining patients (61%) had low posttreatment probability of NRM, based on their treatment scores.

“High-risk patients were significantly less likely to respond to treatment than low-risk patients,” she said, noting that very similar results were found in a validation cohort of the remaining 142 patients, which had a similar proportion of high- and low-risk patients as did the test cohort.

The overall 6-month NRM for patients treated for GVHD was 27% in the test cohort. When the biomarker algorithm was used to separate the cohort into high- and low-risk groups, the NRM rate was found to be approximately 4 times higher among the high-risk patients than among the low-risk patients.

Overall survival was also significantly worse among high- vs. low-risk patients in both the test and validation cohorts.

“We can conclude that the increased NRM seen in the high-risk groups can explain these large differences in overall survival,” Ms. Major-Monfried said.

Because treatment decisions are often made after 1 week based on early clinical response, she and her colleagues also explored whether treatment response after 1 week could similarly predict NRM.

In the test cohort, early response – which includes complete or partial response in GVHD symptoms after 1 week of steroids – was observed in 48% of patients, while 52% were early nonresponders. NRM occurred in 17% of the early responders, compared with 36% of the nonresponders in the test cohort, and similar results were found in the validation cohort.

“These differences are independent of biomarkers,” she noted. “These are solely based on observed clinical response.”

When the biomarker algorithm was applied, prediction of NRM was more precise.

“We started with the early responders,” she explained. “When we used the biomarker algorithm to stratify these patients into high- and low-risk groups, we found that 28% of early responders were actually high risk, and that they experienced 38% NRM – significantly higher than the 8% observed in low-risk patients. Similar results were found again in the validation cohort.”

When the biomarker algorithm was used to stratify patients who were nonresponders at 7 days into high- and low-risk groups, 50% were found to be low risk, and those patients experienced 17% NRM, significantly lower than the 57% seen in the high-risk patients. Similar results were again seen in the validation cohort.

“Early responders with high posttreatment probability have high NRM, and perhaps should not be tapered despite the improvement of their clinical symptoms, while early nonresponders with low posttreatment probability have lower NRM and may not need treatment escalation,” Ms. Major-Monfried said.

“In data not shown, many of these patients are actually what we could call ‘slow responders’ who ultimately fare well,” she noted.

Ms. Major-Monfried reported having no disclosures.

[email protected]

ORLANDO – A biomarker algorithm was better than was clinical response at predicting outcomes after 1 week of systemic steroid treatment for graft-versus-host disease, according to findings from a multicenter study.

The findings have implications for early decision making regarding treatment course, Hannah Major-Monfried reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“The same GVHD algorithm that stratifies patients at day 7 after transplant, at [GVHD] diagnosis, also stratifies them after 1 week of steroid treatment into two groups with distinct risks for treatment failure, 6-month nonrelapse mortality, and overall survival,” she said.

The biomarker algorithm, which includes measures of ST2 and REG3-alpha, was previously shown to predict day-28 treatment response and 6-month non-relapse mortality (NRM) when applied at day 7 post transplant before the onset of GVHD and at the time of diagnosis, said Ms. Major-Monfried, a third-year medical student at Icahn School of Medicine at Mount Sinai, New York.

For the current analysis, levels of the biomarkers were measured after 1 week of treatment in 378 patients with acute GVHD from 11 centers in the Mount Sinai Acute GVHD International Consortium.

In a test cohort that included 236 of the patients, the measurements were used to generate a new predicted probability, or treatment score, for 6-month NRM, which had a value between 0 and 1.

Of the 236 patients, 93 (39%) were considered to have high posttreatment probability of NRM, and the remaining patients (61%) had low posttreatment probability of NRM, based on their treatment scores.

“High-risk patients were significantly less likely to respond to treatment than low-risk patients,” she said, noting that very similar results were found in a validation cohort of the remaining 142 patients, which had a similar proportion of high- and low-risk patients as did the test cohort.

The overall 6-month NRM for patients treated for GVHD was 27% in the test cohort. When the biomarker algorithm was used to separate the cohort into high- and low-risk groups, the NRM rate was found to be approximately 4 times higher among the high-risk patients than among the low-risk patients.

Overall survival was also significantly worse among high- vs. low-risk patients in both the test and validation cohorts.

“We can conclude that the increased NRM seen in the high-risk groups can explain these large differences in overall survival,” Ms. Major-Monfried said.

Because treatment decisions are often made after 1 week based on early clinical response, she and her colleagues also explored whether treatment response after 1 week could similarly predict NRM.

In the test cohort, early response – which includes complete or partial response in GVHD symptoms after 1 week of steroids – was observed in 48% of patients, while 52% were early nonresponders. NRM occurred in 17% of the early responders, compared with 36% of the nonresponders in the test cohort, and similar results were found in the validation cohort.

“These differences are independent of biomarkers,” she noted. “These are solely based on observed clinical response.”

When the biomarker algorithm was applied, prediction of NRM was more precise.

“We started with the early responders,” she explained. “When we used the biomarker algorithm to stratify these patients into high- and low-risk groups, we found that 28% of early responders were actually high risk, and that they experienced 38% NRM – significantly higher than the 8% observed in low-risk patients. Similar results were found again in the validation cohort.”

When the biomarker algorithm was used to stratify patients who were nonresponders at 7 days into high- and low-risk groups, 50% were found to be low risk, and those patients experienced 17% NRM, significantly lower than the 57% seen in the high-risk patients. Similar results were again seen in the validation cohort.

“Early responders with high posttreatment probability have high NRM, and perhaps should not be tapered despite the improvement of their clinical symptoms, while early nonresponders with low posttreatment probability have lower NRM and may not need treatment escalation,” Ms. Major-Monfried said.

“In data not shown, many of these patients are actually what we could call ‘slow responders’ who ultimately fare well,” she noted.

Ms. Major-Monfried reported having no disclosures.

[email protected]

ORLANDO – A biomarker algorithm was better than was clinical response at predicting outcomes after 1 week of systemic steroid treatment for graft-versus-host disease, according to findings from a multicenter study.

The findings have implications for early decision making regarding treatment course, Hannah Major-Monfried reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“The same GVHD algorithm that stratifies patients at day 7 after transplant, at [GVHD] diagnosis, also stratifies them after 1 week of steroid treatment into two groups with distinct risks for treatment failure, 6-month nonrelapse mortality, and overall survival,” she said.

The biomarker algorithm, which includes measures of ST2 and REG3-alpha, was previously shown to predict day-28 treatment response and 6-month non-relapse mortality (NRM) when applied at day 7 post transplant before the onset of GVHD and at the time of diagnosis, said Ms. Major-Monfried, a third-year medical student at Icahn School of Medicine at Mount Sinai, New York.

For the current analysis, levels of the biomarkers were measured after 1 week of treatment in 378 patients with acute GVHD from 11 centers in the Mount Sinai Acute GVHD International Consortium.

In a test cohort that included 236 of the patients, the measurements were used to generate a new predicted probability, or treatment score, for 6-month NRM, which had a value between 0 and 1.

Of the 236 patients, 93 (39%) were considered to have high posttreatment probability of NRM, and the remaining patients (61%) had low posttreatment probability of NRM, based on their treatment scores.

“High-risk patients were significantly less likely to respond to treatment than low-risk patients,” she said, noting that very similar results were found in a validation cohort of the remaining 142 patients, which had a similar proportion of high- and low-risk patients as did the test cohort.

The overall 6-month NRM for patients treated for GVHD was 27% in the test cohort. When the biomarker algorithm was used to separate the cohort into high- and low-risk groups, the NRM rate was found to be approximately 4 times higher among the high-risk patients than among the low-risk patients.

Overall survival was also significantly worse among high- vs. low-risk patients in both the test and validation cohorts.

“We can conclude that the increased NRM seen in the high-risk groups can explain these large differences in overall survival,” Ms. Major-Monfried said.

Because treatment decisions are often made after 1 week based on early clinical response, she and her colleagues also explored whether treatment response after 1 week could similarly predict NRM.

In the test cohort, early response – which includes complete or partial response in GVHD symptoms after 1 week of steroids – was observed in 48% of patients, while 52% were early nonresponders. NRM occurred in 17% of the early responders, compared with 36% of the nonresponders in the test cohort, and similar results were found in the validation cohort.

“These differences are independent of biomarkers,” she noted. “These are solely based on observed clinical response.”

When the biomarker algorithm was applied, prediction of NRM was more precise.

“We started with the early responders,” she explained. “When we used the biomarker algorithm to stratify these patients into high- and low-risk groups, we found that 28% of early responders were actually high risk, and that they experienced 38% NRM – significantly higher than the 8% observed in low-risk patients. Similar results were found again in the validation cohort.”

When the biomarker algorithm was used to stratify patients who were nonresponders at 7 days into high- and low-risk groups, 50% were found to be low risk, and those patients experienced 17% NRM, significantly lower than the 57% seen in the high-risk patients. Similar results were again seen in the validation cohort.

“Early responders with high posttreatment probability have high NRM, and perhaps should not be tapered despite the improvement of their clinical symptoms, while early nonresponders with low posttreatment probability have lower NRM and may not need treatment escalation,” Ms. Major-Monfried said.

“In data not shown, many of these patients are actually what we could call ‘slow responders’ who ultimately fare well,” she noted.

Ms. Major-Monfried reported having no disclosures.

[email protected]

The most up-to-date surgical management for lung cancer, the mediastinum and pleura, and the esophagus, will be featured in Sunday’s full-day symposium “Thoracic Surgery 2017 – State of the Art.”

“We will cover not only standard practice and a lot of the major clinical issues that come up in general thoracic surgery but also discuss new developments and directions for thoracic diseases,” said Seth D. Force, MD, of Emory University, course co-chair. “It’s hard for everyone to stay up to date on everything, especially with a lot of the modern techniques and changes in treatment plans. Things are changing pretty quickly. Presentations by the leading experts in our field will help bring participants up to speed on the latest treatments for different thoracic diseases.”

The most up-to-date surgical management for lung cancer, the mediastinum and pleura, and the esophagus, will be featured in Sunday’s full-day symposium “Thoracic Surgery 2017 – State of the Art.”

“We will cover not only standard practice and a lot of the major clinical issues that come up in general thoracic surgery but also discuss new developments and directions for thoracic diseases,” said Seth D. Force, MD, of Emory University, course co-chair. “It’s hard for everyone to stay up to date on everything, especially with a lot of the modern techniques and changes in treatment plans. Things are changing pretty quickly. Presentations by the leading experts in our field will help bring participants up to speed on the latest treatments for different thoracic diseases.”

The most up-to-date surgical management for lung cancer, the mediastinum and pleura, and the esophagus, will be featured in Sunday’s full-day symposium “Thoracic Surgery 2017 – State of the Art.”

“We will cover not only standard practice and a lot of the major clinical issues that come up in general thoracic surgery but also discuss new developments and directions for thoracic diseases,” said Seth D. Force, MD, of Emory University, course co-chair. “It’s hard for everyone to stay up to date on everything, especially with a lot of the modern techniques and changes in treatment plans. Things are changing pretty quickly. Presentations by the leading experts in our field will help bring participants up to speed on the latest treatments for different thoracic diseases.”

Floors in hospital patients’ rooms are frequently contaminated with pathogens such as Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci, which are easily transmitted to the hands of patients, care providers, and visitors, according to a report published in the American Journal of Infection Control.

Disinfection usually focuses on surfaces that are frequently touched by patients’ or health care workers’ hands, such as bed rails and call buttons. Floor disinfection has received limited attention.

However, floors are frequently touched by objects that are then handled, such as shoes and socks, said Abhishek Deshpande, MD, PhD, of the Cleveland Clinic, and his associates.

To examine the extent of floor contamination and the potential for transfer of pathogens to hands, the investigators surveyed five Cleveland-area hospitals.

Andrei Malov/Thinkstock

Floors in hospital patients’ rooms are frequently contaminated with pathogens such as Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci, which are easily transmitted to the hands of patients, care providers, and visitors, according to a report published in the American Journal of Infection Control.

Disinfection usually focuses on surfaces that are frequently touched by patients’ or health care workers’ hands, such as bed rails and call buttons. Floor disinfection has received limited attention.

However, floors are frequently touched by objects that are then handled, such as shoes and socks, said Abhishek Deshpande, MD, PhD, of the Cleveland Clinic, and his associates.

To examine the extent of floor contamination and the potential for transfer of pathogens to hands, the investigators surveyed five Cleveland-area hospitals.

Andrei Malov/Thinkstock

Floors in hospital patients’ rooms are frequently contaminated with pathogens such as Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci, which are easily transmitted to the hands of patients, care providers, and visitors, according to a report published in the American Journal of Infection Control.

Disinfection usually focuses on surfaces that are frequently touched by patients’ or health care workers’ hands, such as bed rails and call buttons. Floor disinfection has received limited attention.

However, floors are frequently touched by objects that are then handled, such as shoes and socks, said Abhishek Deshpande, MD, PhD, of the Cleveland Clinic, and his associates.

To examine the extent of floor contamination and the potential for transfer of pathogens to hands, the investigators surveyed five Cleveland-area hospitals.

Andrei Malov/Thinkstock

WAILEA, HAWAII – In an era when affordable health insurance could become increasingly tough to come by, it’s worth emphasizing that methotrexate is the most cost-effective way to manage extensive psoriasis – and the liquid formulation designed for intramuscular injection can be taken orally to reduce the cost even further, according to Craig L. Leonardi, MD.

“The absolute cheapest way to manage the patient who has no insurance and has bad psoriasis is to put him on methotrexate and teach him how to draw the liquid solution up in a syringe, dump it in a cup of juice, and drink it,” Dr. Leonardi said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Research Foundation. “The bioavailability is equivalent to [that of] the tablets, and it’s only about one-tenth the cost.”

He urged his fellow dermatologists not to forget about methotrexate in the current flashy era of highly effective – and very expensive – biologic therapies for psoriasis.

“I was thinking methotrexate was going to go away, but it turns out I rely more on that drug than ever before. It’s very useful, and it’s safe if used correctly,” said Dr. Leonardi, a dermatologist at Saint Louis University and a prominent clinical trialist.

He highlighted numerous clinical scenarios in which methotrexate remains a valuable treatment in patients with moderate to severe psoriasis. He also touched on patient monitoring requirements, adverse events, and common reasons he receives referrals from physicians whose patients seem to be having problems on methotrexate – referrals that, in most cases, could be avoided, he said, if the referring physician had a fuller understanding of the drug.

“Patients are referred to me all the time for methotrexate intolerance,” Dr. Leonardi said. “When you take methotrexate, you get a brief, dramatic spike in transaminase levels that peaks within a day and then drops off. But, when you get lab tests in these patients, you want to look at trough levels. You want to see the best liver function test values for the week.

“That means you have to tell the patient what day to take the drug and what day to get labs drawn,” he continued. “I’m here to tell you that the vast majority of issues that I see where patients have elevated liver function tests involves them getting their testing done in the first 4 days after taking methotrexate. Take the time to ask about this, and I think you’ll be pleasantly surprised.

“If you just make an adjustment and get them on the right schedule, you’ll discover that the patient is tolerating the drug just fine,” Dr. Leonardi added. “We like getting labs on Monday and dosing on Tuesday.”

Methotrexate’s half-life is 3-15 hours. Psoriasis is often controlled at a methotrexate dose of about 15 mg/week.

Methotrexate’s advantages include ease of use. It’s a straightforward matter to start and stop the drug and to make small dose adjustments. Methotrexate comes in a variety of formulations: the 2.5-mg tablets, the 25 mg/mL solution for IM injection, and prefilled autoinjector devices for subcutaneous administration.

These preloaded pens for subcutaneous injection are just as effective as IM therapy, Dr. Leonardi said. Methotrexate is also better absorbed subcutaneously than it is orally. The bioavailability of oral methotrexate plateaus at a dose of about 22 mg/week, while subcutaneously delivered methotrexate does not. So, if a patient’s psoriasis isn’t adequately controlled on higher-dose oral therapy, it’s worth considering a switch to the preloaded pens.

“It’s a very simple injection, very cost-effective, and your patients may get more bang for the buck by doing that,” according to the dermatologist.

Also, nausea, vomiting, diarrhea, and abdominal pain have been shown to be significantly less frequent and intense with subcutaneous methotrexate than with the tablets. So, if a patient is experiencing limiting gastrointestinal issues on methotrexate tablets, a shift to subcutaneous therapy is often the solution.

What kind of efficacy can physicians expect with methotrexate monotherapy?

Dr. Leonardi cited the results of the European randomized, open-label RESTORE-1 trial (Br J Dermatol. 2011 Nov;165[5]:1109-17) as being consistent with his own extensive clinical experience: a week-16 PASI (Psoriasis Area and Severity Index ) 75 response rate of 42% with methotrexate, compared with 78% for infliximab (Remicade).

Of course, some patients can’t receive a biologic agent because of their age, lack of insurance coverage, or medical contraindications.

“I use methotrexate a lot in Medicare patients, where, with Part D, it’s hard to get access to biologics without really good coinsurance. I think all of us who prescribe biologics understand that,” he observed.

In pediatric patients with extensive psoriasis, he turns to methotrexate as first-line systemic therapy. After 3 months, if the young patient hasn’t responded satisfactorily, Dr. Leonardi asks the insurance company for access to a biologic agent and usually gets it.

Methotrexate really shines in combination with a biologic agent. It inhibits formation of antibiologic antibodies, an important cause of loss of effectiveness of monoclonal antibody therapy.

In one study, 28% of patients on adalimumab (Humira) developed antiadalimumab antibodies during the first 3 years of therapy. These patients were more likely to drop out of therapy for lack of effectiveness.

A key finding in this study was that two-thirds of patients who developed antiadalimumab antibodies did so during the first 28 weeks of therapy (JAMA. 2011 Apr 13;305[14]:1460-8). This time line has influenced Dr. Leonardi’s own clinical practice. He routinely keeps patients on methotrexate for their first 28-36 weeks on a biologic, then tapers the methotrexate in favor of biologic monotherapy.

Other benefits and guidelines

Methotrexate is also a boon in managing psoriasis flares in patients on a biologic.

“We’ve all had patients who are doing well on a biologic, they’re cruising along at 140 weeks, then they get strep throat or another infection, and, next thing you know, you have destabilized psoriasis,” Dr. Leonardi noted.

“One thing I’ll do is add methotrexate to the mix, try to get things under control, and, if we do, then we’ll try to taper the methotrexate,” he continued. “That whole episode might take 4-6 months to resolve before the patient might be able to tolerate biologic monotherapy, though. If they can’t at that point, you might consider rotating to another biologic.”

Current American Academy of Dermatology guidelines recommend that women on methotrexate limit their alcohol intake to one drink per day, two drinks for men. British Society for Rheumatology guidelines recommend a ceiling of 32 g to 64 g of ethanol per week.

“We don’t insist on abstinence. There’s no good evidence that it’s needed,” Dr. Leonardi noted. “If you dose this drug on Tuesday, you can be sure that it’s eliminated from the body on Friday, and that’s when I’ll generally green-light patients to socialize over the weekend. If you can make life a little more tolerable for your patients and they’re willing to follow your instructions, I think it’s a better deal all the way around.”

Prior to initiating methotrexate, he obtains a CBC with platelet count, liver function tests, serum urea nitrogen, creatinine, and screens for latent tuberculosis. In terms of on-treatment monitoring, he gets a CBC and liver function tests every 4-12 weeks and keeps an eye on renal function, especially in older patients, because methotrexate is eliminated renally.

“The guidelines have relaxed regarding the need for liver biopsies,” Dr. Leonardi said. “Most of us are not getting liver biopsies anymore, as is true of our friends in rheumatology.”

He reported having financial relationships with more than a dozen pharmaceutical companies. The SDEF and this news organization are owned by the same parent company.

[email protected]

WAILEA, HAWAII – In an era when affordable health insurance could become increasingly tough to come by, it’s worth emphasizing that methotrexate is the most cost-effective way to manage extensive psoriasis – and the liquid formulation designed for intramuscular injection can be taken orally to reduce the cost even further, according to Craig L. Leonardi, MD.

“The absolute cheapest way to manage the patient who has no insurance and has bad psoriasis is to put him on methotrexate and teach him how to draw the liquid solution up in a syringe, dump it in a cup of juice, and drink it,” Dr. Leonardi said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Research Foundation. “The bioavailability is equivalent to [that of] the tablets, and it’s only about one-tenth the cost.”

He urged his fellow dermatologists not to forget about methotrexate in the current flashy era of highly effective – and very expensive – biologic therapies for psoriasis.

“I was thinking methotrexate was going to go away, but it turns out I rely more on that drug than ever before. It’s very useful, and it’s safe if used correctly,” said Dr. Leonardi, a dermatologist at Saint Louis University and a prominent clinical trialist.

He highlighted numerous clinical scenarios in which methotrexate remains a valuable treatment in patients with moderate to severe psoriasis. He also touched on patient monitoring requirements, adverse events, and common reasons he receives referrals from physicians whose patients seem to be having problems on methotrexate – referrals that, in most cases, could be avoided, he said, if the referring physician had a fuller understanding of the drug.

“Patients are referred to me all the time for methotrexate intolerance,” Dr. Leonardi said. “When you take methotrexate, you get a brief, dramatic spike in transaminase levels that peaks within a day and then drops off. But, when you get lab tests in these patients, you want to look at trough levels. You want to see the best liver function test values for the week.

“That means you have to tell the patient what day to take the drug and what day to get labs drawn,” he continued. “I’m here to tell you that the vast majority of issues that I see where patients have elevated liver function tests involves them getting their testing done in the first 4 days after taking methotrexate. Take the time to ask about this, and I think you’ll be pleasantly surprised.

“If you just make an adjustment and get them on the right schedule, you’ll discover that the patient is tolerating the drug just fine,” Dr. Leonardi added. “We like getting labs on Monday and dosing on Tuesday.”

Methotrexate’s half-life is 3-15 hours. Psoriasis is often controlled at a methotrexate dose of about 15 mg/week.

Methotrexate’s advantages include ease of use. It’s a straightforward matter to start and stop the drug and to make small dose adjustments. Methotrexate comes in a variety of formulations: the 2.5-mg tablets, the 25 mg/mL solution for IM injection, and prefilled autoinjector devices for subcutaneous administration.

These preloaded pens for subcutaneous injection are just as effective as IM therapy, Dr. Leonardi said. Methotrexate is also better absorbed subcutaneously than it is orally. The bioavailability of oral methotrexate plateaus at a dose of about 22 mg/week, while subcutaneously delivered methotrexate does not. So, if a patient’s psoriasis isn’t adequately controlled on higher-dose oral therapy, it’s worth considering a switch to the preloaded pens.

“It’s a very simple injection, very cost-effective, and your patients may get more bang for the buck by doing that,” according to the dermatologist.

Also, nausea, vomiting, diarrhea, and abdominal pain have been shown to be significantly less frequent and intense with subcutaneous methotrexate than with the tablets. So, if a patient is experiencing limiting gastrointestinal issues on methotrexate tablets, a shift to subcutaneous therapy is often the solution.

What kind of efficacy can physicians expect with methotrexate monotherapy?

Dr. Leonardi cited the results of the European randomized, open-label RESTORE-1 trial (Br J Dermatol. 2011 Nov;165[5]:1109-17) as being consistent with his own extensive clinical experience: a week-16 PASI (Psoriasis Area and Severity Index ) 75 response rate of 42% with methotrexate, compared with 78% for infliximab (Remicade).

Of course, some patients can’t receive a biologic agent because of their age, lack of insurance coverage, or medical contraindications.

“I use methotrexate a lot in Medicare patients, where, with Part D, it’s hard to get access to biologics without really good coinsurance. I think all of us who prescribe biologics understand that,” he observed.

In pediatric patients with extensive psoriasis, he turns to methotrexate as first-line systemic therapy. After 3 months, if the young patient hasn’t responded satisfactorily, Dr. Leonardi asks the insurance company for access to a biologic agent and usually gets it.

Methotrexate really shines in combination with a biologic agent. It inhibits formation of antibiologic antibodies, an important cause of loss of effectiveness of monoclonal antibody therapy.

In one study, 28% of patients on adalimumab (Humira) developed antiadalimumab antibodies during the first 3 years of therapy. These patients were more likely to drop out of therapy for lack of effectiveness.

A key finding in this study was that two-thirds of patients who developed antiadalimumab antibodies did so during the first 28 weeks of therapy (JAMA. 2011 Apr 13;305[14]:1460-8). This time line has influenced Dr. Leonardi’s own clinical practice. He routinely keeps patients on methotrexate for their first 28-36 weeks on a biologic, then tapers the methotrexate in favor of biologic monotherapy.

Other benefits and guidelines

Methotrexate is also a boon in managing psoriasis flares in patients on a biologic.

“We’ve all had patients who are doing well on a biologic, they’re cruising along at 140 weeks, then they get strep throat or another infection, and, next thing you know, you have destabilized psoriasis,” Dr. Leonardi noted.

“One thing I’ll do is add methotrexate to the mix, try to get things under control, and, if we do, then we’ll try to taper the methotrexate,” he continued. “That whole episode might take 4-6 months to resolve before the patient might be able to tolerate biologic monotherapy, though. If they can’t at that point, you might consider rotating to another biologic.”

Current American Academy of Dermatology guidelines recommend that women on methotrexate limit their alcohol intake to one drink per day, two drinks for men. British Society for Rheumatology guidelines recommend a ceiling of 32 g to 64 g of ethanol per week.

“We don’t insist on abstinence. There’s no good evidence that it’s needed,” Dr. Leonardi noted. “If you dose this drug on Tuesday, you can be sure that it’s eliminated from the body on Friday, and that’s when I’ll generally green-light patients to socialize over the weekend. If you can make life a little more tolerable for your patients and they’re willing to follow your instructions, I think it’s a better deal all the way around.”

Prior to initiating methotrexate, he obtains a CBC with platelet count, liver function tests, serum urea nitrogen, creatinine, and screens for latent tuberculosis. In terms of on-treatment monitoring, he gets a CBC and liver function tests every 4-12 weeks and keeps an eye on renal function, especially in older patients, because methotrexate is eliminated renally.

“The guidelines have relaxed regarding the need for liver biopsies,” Dr. Leonardi said. “Most of us are not getting liver biopsies anymore, as is true of our friends in rheumatology.”

He reported having financial relationships with more than a dozen pharmaceutical companies. The SDEF and this news organization are owned by the same parent company.

[email protected]

WAILEA, HAWAII – In an era when affordable health insurance could become increasingly tough to come by, it’s worth emphasizing that methotrexate is the most cost-effective way to manage extensive psoriasis – and the liquid formulation designed for intramuscular injection can be taken orally to reduce the cost even further, according to Craig L. Leonardi, MD.

“The absolute cheapest way to manage the patient who has no insurance and has bad psoriasis is to put him on methotrexate and teach him how to draw the liquid solution up in a syringe, dump it in a cup of juice, and drink it,” Dr. Leonardi said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Research Foundation. “The bioavailability is equivalent to [that of] the tablets, and it’s only about one-tenth the cost.”

He urged his fellow dermatologists not to forget about methotrexate in the current flashy era of highly effective – and very expensive – biologic therapies for psoriasis.

“I was thinking methotrexate was going to go away, but it turns out I rely more on that drug than ever before. It’s very useful, and it’s safe if used correctly,” said Dr. Leonardi, a dermatologist at Saint Louis University and a prominent clinical trialist.

He highlighted numerous clinical scenarios in which methotrexate remains a valuable treatment in patients with moderate to severe psoriasis. He also touched on patient monitoring requirements, adverse events, and common reasons he receives referrals from physicians whose patients seem to be having problems on methotrexate – referrals that, in most cases, could be avoided, he said, if the referring physician had a fuller understanding of the drug.

“Patients are referred to me all the time for methotrexate intolerance,” Dr. Leonardi said. “When you take methotrexate, you get a brief, dramatic spike in transaminase levels that peaks within a day and then drops off. But, when you get lab tests in these patients, you want to look at trough levels. You want to see the best liver function test values for the week.

“That means you have to tell the patient what day to take the drug and what day to get labs drawn,” he continued. “I’m here to tell you that the vast majority of issues that I see where patients have elevated liver function tests involves them getting their testing done in the first 4 days after taking methotrexate. Take the time to ask about this, and I think you’ll be pleasantly surprised.

“If you just make an adjustment and get them on the right schedule, you’ll discover that the patient is tolerating the drug just fine,” Dr. Leonardi added. “We like getting labs on Monday and dosing on Tuesday.”

Methotrexate’s half-life is 3-15 hours. Psoriasis is often controlled at a methotrexate dose of about 15 mg/week.

Methotrexate’s advantages include ease of use. It’s a straightforward matter to start and stop the drug and to make small dose adjustments. Methotrexate comes in a variety of formulations: the 2.5-mg tablets, the 25 mg/mL solution for IM injection, and prefilled autoinjector devices for subcutaneous administration.

These preloaded pens for subcutaneous injection are just as effective as IM therapy, Dr. Leonardi said. Methotrexate is also better absorbed subcutaneously than it is orally. The bioavailability of oral methotrexate plateaus at a dose of about 22 mg/week, while subcutaneously delivered methotrexate does not. So, if a patient’s psoriasis isn’t adequately controlled on higher-dose oral therapy, it’s worth considering a switch to the preloaded pens.

“It’s a very simple injection, very cost-effective, and your patients may get more bang for the buck by doing that,” according to the dermatologist.

Also, nausea, vomiting, diarrhea, and abdominal pain have been shown to be significantly less frequent and intense with subcutaneous methotrexate than with the tablets. So, if a patient is experiencing limiting gastrointestinal issues on methotrexate tablets, a shift to subcutaneous therapy is often the solution.

What kind of efficacy can physicians expect with methotrexate monotherapy?

Dr. Leonardi cited the results of the European randomized, open-label RESTORE-1 trial (Br J Dermatol. 2011 Nov;165[5]:1109-17) as being consistent with his own extensive clinical experience: a week-16 PASI (Psoriasis Area and Severity Index ) 75 response rate of 42% with methotrexate, compared with 78% for infliximab (Remicade).

Of course, some patients can’t receive a biologic agent because of their age, lack of insurance coverage, or medical contraindications.

“I use methotrexate a lot in Medicare patients, where, with Part D, it’s hard to get access to biologics without really good coinsurance. I think all of us who prescribe biologics understand that,” he observed.

In pediatric patients with extensive psoriasis, he turns to methotrexate as first-line systemic therapy. After 3 months, if the young patient hasn’t responded satisfactorily, Dr. Leonardi asks the insurance company for access to a biologic agent and usually gets it.

Methotrexate really shines in combination with a biologic agent. It inhibits formation of antibiologic antibodies, an important cause of loss of effectiveness of monoclonal antibody therapy.

In one study, 28% of patients on adalimumab (Humira) developed antiadalimumab antibodies during the first 3 years of therapy. These patients were more likely to drop out of therapy for lack of effectiveness.

A key finding in this study was that two-thirds of patients who developed antiadalimumab antibodies did so during the first 28 weeks of therapy (JAMA. 2011 Apr 13;305[14]:1460-8). This time line has influenced Dr. Leonardi’s own clinical practice. He routinely keeps patients on methotrexate for their first 28-36 weeks on a biologic, then tapers the methotrexate in favor of biologic monotherapy.

Other benefits and guidelines

Methotrexate is also a boon in managing psoriasis flares in patients on a biologic.

“We’ve all had patients who are doing well on a biologic, they’re cruising along at 140 weeks, then they get strep throat or another infection, and, next thing you know, you have destabilized psoriasis,” Dr. Leonardi noted.

“One thing I’ll do is add methotrexate to the mix, try to get things under control, and, if we do, then we’ll try to taper the methotrexate,” he continued. “That whole episode might take 4-6 months to resolve before the patient might be able to tolerate biologic monotherapy, though. If they can’t at that point, you might consider rotating to another biologic.”

Current American Academy of Dermatology guidelines recommend that women on methotrexate limit their alcohol intake to one drink per day, two drinks for men. British Society for Rheumatology guidelines recommend a ceiling of 32 g to 64 g of ethanol per week.

“We don’t insist on abstinence. There’s no good evidence that it’s needed,” Dr. Leonardi noted. “If you dose this drug on Tuesday, you can be sure that it’s eliminated from the body on Friday, and that’s when I’ll generally green-light patients to socialize over the weekend. If you can make life a little more tolerable for your patients and they’re willing to follow your instructions, I think it’s a better deal all the way around.”

Prior to initiating methotrexate, he obtains a CBC with platelet count, liver function tests, serum urea nitrogen, creatinine, and screens for latent tuberculosis. In terms of on-treatment monitoring, he gets a CBC and liver function tests every 4-12 weeks and keeps an eye on renal function, especially in older patients, because methotrexate is eliminated renally.

“The guidelines have relaxed regarding the need for liver biopsies,” Dr. Leonardi said. “Most of us are not getting liver biopsies anymore, as is true of our friends in rheumatology.”

He reported having financial relationships with more than a dozen pharmaceutical companies. The SDEF and this news organization are owned by the same parent company.

[email protected]

The rate of paid legal claims against physicians dropped by more than half between 1992 and 2014, but the average claim payment amount rose, according to an analysis of the National Practitioner Data Bank.

Adam C. Schaffer, MD, of Brigham and Women’s Hospital, Boston, and his colleagues examined paid claims from the National Practitioner Data Bank from Jan. 1, 1992, to Dec. 31, 2014, accounting for specialty. Dollar amounts were inflation-adjusted to 2014 dollars using the Consumer Price Index.

The most common allegation was diagnostic error, followed by surgical error and medication or treatment error. The proportion of paid claims attributable to diagnostic error varied widely and was highest in pathology and radiology. Plastic surgery had the highest percentage of paid claims related to surgical errors. Specialties with the highest percentage of paid claims related to medication/treatment errors were psychiatry, general practice, and pulmonology.

While prior data have shown the overall trend of declining paid malpractice claims and increasing average payments, this study is the first to examine such trends by medical specialty, said Dr. Schaffer.

“We think it is important to try to understand the reasons for the variation among specialties in characteristics of paid malpractice claims, as understanding the reasons for this variation may provide insights about how we can provide the safest care possible,” he said in an interview.

Dr. Schaffer said that he hopes the findings make physicians more aware of the malpractice landscape and aid their future practice decisions.

“Medical malpractice is an issue that concerns many physicians, and physicians’ perceptions of their liability risk can influence the decisions they make in caring for their patients,” he said. “By performing an analysis of a national database of paid medical malpractice claims broken down by specialty, we hope to provide physicians with data that give them an accurate picture of the medical malpractice environment in which they are practicing.”

[email protected]

On Twitter @legal_med

The rate of paid legal claims against physicians dropped by more than half between 1992 and 2014, but the average claim payment amount rose, according to an analysis of the National Practitioner Data Bank.

Adam C. Schaffer, MD, of Brigham and Women’s Hospital, Boston, and his colleagues examined paid claims from the National Practitioner Data Bank from Jan. 1, 1992, to Dec. 31, 2014, accounting for specialty. Dollar amounts were inflation-adjusted to 2014 dollars using the Consumer Price Index.

The most common allegation was diagnostic error, followed by surgical error and medication or treatment error. The proportion of paid claims attributable to diagnostic error varied widely and was highest in pathology and radiology. Plastic surgery had the highest percentage of paid claims related to surgical errors. Specialties with the highest percentage of paid claims related to medication/treatment errors were psychiatry, general practice, and pulmonology.

While prior data have shown the overall trend of declining paid malpractice claims and increasing average payments, this study is the first to examine such trends by medical specialty, said Dr. Schaffer.

“We think it is important to try to understand the reasons for the variation among specialties in characteristics of paid malpractice claims, as understanding the reasons for this variation may provide insights about how we can provide the safest care possible,” he said in an interview.

Dr. Schaffer said that he hopes the findings make physicians more aware of the malpractice landscape and aid their future practice decisions.

“Medical malpractice is an issue that concerns many physicians, and physicians’ perceptions of their liability risk can influence the decisions they make in caring for their patients,” he said. “By performing an analysis of a national database of paid medical malpractice claims broken down by specialty, we hope to provide physicians with data that give them an accurate picture of the medical malpractice environment in which they are practicing.”

[email protected]

On Twitter @legal_med

The rate of paid legal claims against physicians dropped by more than half between 1992 and 2014, but the average claim payment amount rose, according to an analysis of the National Practitioner Data Bank.

Adam C. Schaffer, MD, of Brigham and Women’s Hospital, Boston, and his colleagues examined paid claims from the National Practitioner Data Bank from Jan. 1, 1992, to Dec. 31, 2014, accounting for specialty. Dollar amounts were inflation-adjusted to 2014 dollars using the Consumer Price Index.

The most common allegation was diagnostic error, followed by surgical error and medication or treatment error. The proportion of paid claims attributable to diagnostic error varied widely and was highest in pathology and radiology. Plastic surgery had the highest percentage of paid claims related to surgical errors. Specialties with the highest percentage of paid claims related to medication/treatment errors were psychiatry, general practice, and pulmonology.

While prior data have shown the overall trend of declining paid malpractice claims and increasing average payments, this study is the first to examine such trends by medical specialty, said Dr. Schaffer.

“We think it is important to try to understand the reasons for the variation among specialties in characteristics of paid malpractice claims, as understanding the reasons for this variation may provide insights about how we can provide the safest care possible,” he said in an interview.

Dr. Schaffer said that he hopes the findings make physicians more aware of the malpractice landscape and aid their future practice decisions.

“Medical malpractice is an issue that concerns many physicians, and physicians’ perceptions of their liability risk can influence the decisions they make in caring for their patients,” he said. “By performing an analysis of a national database of paid medical malpractice claims broken down by specialty, we hope to provide physicians with data that give them an accurate picture of the medical malpractice environment in which they are practicing.”

[email protected]

On Twitter @legal_med

As the premier organization focused on extracorporeal circulation technology professionals, AmSECT encourages sharing of the latest trends and developments in the industry. When visiting the Exhibit Hall, stroll over to AmSECT Avenue and explore perfusion technologies and products – all in one place!

Walk the red carpet and meet with Abbott, Spectrum Medical, Medtronic, LivaNova, Terumo and more! See first-hand the latest in perfusion technology and advancements. You’ll gain knowledge of products that you can immediately take back to your facility, and other advancements that will help you remain current in the field of perfusion.

Stop by the AmSECT booth to discover how to keep learning after the conference concludes! AmSECT University provides a platform to facilitate perfusion-related education and earn continuing education units. The AmSECT team is available to answer your questions about AmSECT University and other benefits you will receive by becoming an AmSECT member.

As the premier organization focused on extracorporeal circulation technology professionals, AmSECT encourages sharing of the latest trends and developments in the industry. When visiting the Exhibit Hall, stroll over to AmSECT Avenue and explore perfusion technologies and products – all in one place!

Walk the red carpet and meet with Abbott, Spectrum Medical, Medtronic, LivaNova, Terumo and more! See first-hand the latest in perfusion technology and advancements. You’ll gain knowledge of products that you can immediately take back to your facility, and other advancements that will help you remain current in the field of perfusion.

Stop by the AmSECT booth to discover how to keep learning after the conference concludes! AmSECT University provides a platform to facilitate perfusion-related education and earn continuing education units. The AmSECT team is available to answer your questions about AmSECT University and other benefits you will receive by becoming an AmSECT member.

As the premier organization focused on extracorporeal circulation technology professionals, AmSECT encourages sharing of the latest trends and developments in the industry. When visiting the Exhibit Hall, stroll over to AmSECT Avenue and explore perfusion technologies and products – all in one place!

Walk the red carpet and meet with Abbott, Spectrum Medical, Medtronic, LivaNova, Terumo and more! See first-hand the latest in perfusion technology and advancements. You’ll gain knowledge of products that you can immediately take back to your facility, and other advancements that will help you remain current in the field of perfusion.

Stop by the AmSECT booth to discover how to keep learning after the conference concludes! AmSECT University provides a platform to facilitate perfusion-related education and earn continuing education units. The AmSECT team is available to answer your questions about AmSECT University and other benefits you will receive by becoming an AmSECT member.

Saturday’s course “Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure: Mastery of the Management of End Stage Heart and Lung Disease” will explore novel techniques in heart and lung transplant, mechanical circulatory support, and extracorporeal membrane oxygenation (ECMO). The course is co-chaired by Matthew D. Bacchetta, MD, of Columbia University, Carmelo A. Milano, of Duke University, and Rich Walczak, CCP, FPP, also of Duke University.

The first session will focus on heart transplants, and will cover topics such as perfusion storage for transplantation, maintaining an ex-vivo heart, primary graft dysfunction and a talk from Yoshifumi Naka, MD, of Columbia University, who will provide first-hand accounts of using the latest durable centrifugal left ventricular assist device (LVAD).

Saturday’s course “Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure: Mastery of the Management of End Stage Heart and Lung Disease” will explore novel techniques in heart and lung transplant, mechanical circulatory support, and extracorporeal membrane oxygenation (ECMO). The course is co-chaired by Matthew D. Bacchetta, MD, of Columbia University, Carmelo A. Milano, of Duke University, and Rich Walczak, CCP, FPP, also of Duke University.

The first session will focus on heart transplants, and will cover topics such as perfusion storage for transplantation, maintaining an ex-vivo heart, primary graft dysfunction and a talk from Yoshifumi Naka, MD, of Columbia University, who will provide first-hand accounts of using the latest durable centrifugal left ventricular assist device (LVAD).

Saturday’s course “Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure: Mastery of the Management of End Stage Heart and Lung Disease” will explore novel techniques in heart and lung transplant, mechanical circulatory support, and extracorporeal membrane oxygenation (ECMO). The course is co-chaired by Matthew D. Bacchetta, MD, of Columbia University, Carmelo A. Milano, of Duke University, and Rich Walczak, CCP, FPP, also of Duke University.

The first session will focus on heart transplants, and will cover topics such as perfusion storage for transplantation, maintaining an ex-vivo heart, primary graft dysfunction and a talk from Yoshifumi Naka, MD, of Columbia University, who will provide first-hand accounts of using the latest durable centrifugal left ventricular assist device (LVAD).

Attendees will have the opportunity to hear about exceptional cardiothoracic research at Monday afternoon’s 20th Annual C. Walton Lillehei Resident Forum, which showcases top research by residents.

Co-chairs Dao Nguyen, MD, of the University of Miami Health System and Frederick Y. Chen, MD, PhD, of Tufts Medical Center, along with members of the AATS Research Scholarship Committee reviewed the submitted manuscripts and will judge the oral presentations to select the winner of a prestigious $5,000 cash prize. The competition is limited to original work presented by residents in cardiothoracic surgery and/or residents in general surgical training programs who are working in a cardiothoracic surgical laboratory or clinical rotation in North America.

Attendees will have the opportunity to hear about exceptional cardiothoracic research at Monday afternoon’s 20th Annual C. Walton Lillehei Resident Forum, which showcases top research by residents.

Co-chairs Dao Nguyen, MD, of the University of Miami Health System and Frederick Y. Chen, MD, PhD, of Tufts Medical Center, along with members of the AATS Research Scholarship Committee reviewed the submitted manuscripts and will judge the oral presentations to select the winner of a prestigious $5,000 cash prize. The competition is limited to original work presented by residents in cardiothoracic surgery and/or residents in general surgical training programs who are working in a cardiothoracic surgical laboratory or clinical rotation in North America.

Attendees will have the opportunity to hear about exceptional cardiothoracic research at Monday afternoon’s 20th Annual C. Walton Lillehei Resident Forum, which showcases top research by residents.

Co-chairs Dao Nguyen, MD, of the University of Miami Health System and Frederick Y. Chen, MD, PhD, of Tufts Medical Center, along with members of the AATS Research Scholarship Committee reviewed the submitted manuscripts and will judge the oral presentations to select the winner of a prestigious $5,000 cash prize. The competition is limited to original work presented by residents in cardiothoracic surgery and/or residents in general surgical training programs who are working in a cardiothoracic surgical laboratory or clinical rotation in North America.

“This year’s Adult Cardiac Surgery Symposium will prove to be one of the most dynamic and liveliest to date,” said course chair Vinod H. Thourani, MD, in an interview. “Each session will have dedicated time for robust panel discussion and hopefully significant participant involvement,” he said.

Dr. Thourani, of Emory University, leads an expert roster of clinicians in the AATS/STS Adult Cardiac Surgery Symposium entitled “Excellence Through Knowledge.” The all-day Sunday format allows for an in-depth exploration that can benefit clinicians with a range of perspectives. The talks will include not only examples from clinical experience, but also “will provide the audience with the most up-to-date literature on a variety of topics relevant to the practice of cardiac surgery,” Dr. Thourani said.

“This year’s Adult Cardiac Surgery Symposium will prove to be one of the most dynamic and liveliest to date,” said course chair Vinod H. Thourani, MD, in an interview. “Each session will have dedicated time for robust panel discussion and hopefully significant participant involvement,” he said.

Dr. Thourani, of Emory University, leads an expert roster of clinicians in the AATS/STS Adult Cardiac Surgery Symposium entitled “Excellence Through Knowledge.” The all-day Sunday format allows for an in-depth exploration that can benefit clinicians with a range of perspectives. The talks will include not only examples from clinical experience, but also “will provide the audience with the most up-to-date literature on a variety of topics relevant to the practice of cardiac surgery,” Dr. Thourani said.

“This year’s Adult Cardiac Surgery Symposium will prove to be one of the most dynamic and liveliest to date,” said course chair Vinod H. Thourani, MD, in an interview. “Each session will have dedicated time for robust panel discussion and hopefully significant participant involvement,” he said.

Dr. Thourani, of Emory University, leads an expert roster of clinicians in the AATS/STS Adult Cardiac Surgery Symposium entitled “Excellence Through Knowledge.” The all-day Sunday format allows for an in-depth exploration that can benefit clinicians with a range of perspectives. The talks will include not only examples from clinical experience, but also “will provide the audience with the most up-to-date literature on a variety of topics relevant to the practice of cardiac surgery,” Dr. Thourani said.

The smallest patients get a full day’s focus in the “Congenital Heart Disease Symposium: Innovations and Controversies in the Surgical Management of Congenital Heart Disease,” session on Sunday, April 30.

“This symposium is designed for participants to get up-to-date information about cardiothoracic surgery,” said Katsuhide Maeda, MD, of Stanford University Medical Center, in an interview.

The smallest patients get a full day’s focus in the “Congenital Heart Disease Symposium: Innovations and Controversies in the Surgical Management of Congenital Heart Disease,” session on Sunday, April 30.

“This symposium is designed for participants to get up-to-date information about cardiothoracic surgery,” said Katsuhide Maeda, MD, of Stanford University Medical Center, in an interview.

The smallest patients get a full day’s focus in the “Congenital Heart Disease Symposium: Innovations and Controversies in the Surgical Management of Congenital Heart Disease,” session on Sunday, April 30.

“This symposium is designed for participants to get up-to-date information about cardiothoracic surgery,” said Katsuhide Maeda, MD, of Stanford University Medical Center, in an interview.