Rheumatology News

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

gtwachtman@mdedge.com

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

gtwachtman@mdedge.com

The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.

“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”

“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”

The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.

“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”

The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.

Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.

“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”

Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.

Dr. Edgerton highlighted why this agreement between the two agencies is so important.

“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”

Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.

The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.

gtwachtman@mdedge.com

Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.

copyright Joss/Fotolia.com

“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D₃ (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D₃.

The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.

At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.

The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.

At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.

Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm² greater total BMD, compared with those with sufficient vitamin D at baseline.

Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm² higher head BMD, and a mean 12-g higher total BMC.

Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.

The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.

There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.

“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.

Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.

Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.

“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”

She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.

Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.

“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”

Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.

The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.

SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.

Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.

copyright Joss/Fotolia.com

“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D₃ (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D₃.

The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.

At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.

The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.

At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.

Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm² greater total BMD, compared with those with sufficient vitamin D at baseline.

Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm² higher head BMD, and a mean 12-g higher total BMC.

Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.

The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.

There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.

“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.

Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.

Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.

“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”

She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.

Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.

“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”

Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.

The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.

SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.

Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.

copyright Joss/Fotolia.com

“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D₃ (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D₃.

The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.

At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.

The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.

At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.

Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm² greater total BMD, compared with those with sufficient vitamin D at baseline.

Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm² higher head BMD, and a mean 12-g higher total BMC.

Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.

The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.

There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.

“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.

Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.

Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.

“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”

She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.

Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.

“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”

Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.

The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.

SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.

Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.

Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.

To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.

Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.

Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).

No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.

In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.

The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.

“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.

The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.

SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.

Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.

Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.

To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.

Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.

Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).

No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.

In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.

The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.

“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.

The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.

SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.

Psoriasis patients are at increased risk for several types of cancer, notably lymphoma and keratinocyte cancer, based on data from a systematic review and meta-analysis of more than 2 million patients.

Previous studies have identified an increased overall cancer risk in psoriasis patients, compared with the general population or controls without psoriasis, and both lymphomas and keratinocyte cancers occur more often in psoriasis patients, compared with controls, but additional larger studies have been conducted since the last meta-analysis was published in 2013, wrote Sofie Vaengebjerg, MD, of the University of Copenhagen and colleagues.

To better identify the risk of cancer in psoriasis and psoriatic arthritis patients and to explore the impact of biologics, the researchers reviewed data from 112 studies totaling 2,053,932 patients in a study published in JAMA Dermatology.

Overall, the risk of any cancer was slightly higher in psoriasis patients (risk ratio, 1.21; 95% confidence interval, 1.11-1.33), compared with controls, with a prevalence of 4.78% and an incidence rate of 11.75 per 1,000 person-years. The most common cancer among psoriasis patients was keratinocyte cancer, with a risk ratio of 2.28 (95% CI, 1.73-3.01), a prevalence of 2.55%, and an incidence rate of 4.35 per 1,000 person-years.

Other cancers with significantly elevated risk among psoriasis patients were lymphomas (RR, 1.56; 95% CI, 1.37-1.78), lung cancer (RR, 1.26; 95% CI, 1.13-1.40), and bladder cancer (RR, 1.12; 95% CI, 1.04-1.19).

No increased risk of cancer was noted among psoriasis patients who were treated with biologics. “However, patients receiving biologic agents are selected and the results might be reliant on selection bias, and studies investigating long-term safety of these drugs are still limited,” the researchers wrote.

In addition, psoriatic arthritis was not associated with any overall increase in cancer risk, with the exception of three studies showing an increased risk for breast cancer, the researchers noted. The overall cancer prevalence for psoriatic arthritis patients was 5.74%, with an incidence rate of 6.44 per 1,000 person-years.

The study findings were limited by several factors, including the inconsistencies in study design and characteristics and the small amount of data on biologic agents and psoriatic arthritis, the researchers noted. However, the results were strengthened by the large number of patients, real-world study settings, inclusion of biologics, and analysis of cancer in psoriatic arthritis patients.

“Clinicians treating patients with psoriasis should be aware of this increased risk, especially for lymphomas, as immunogenic treatment might be associated with exacerbations,” and should be aware that more research is needed to assess cancer risk associated with biologics, they concluded.

The study received no outside funding. Lead author Dr. Vaengebjerg had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including AbbVie, Janssen, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, and Sanofi.

SOURCE: Vaengebjerg S et al. JAMA Dermatol. 2020 Feb 19. doi:10.1001/jamadermatol.2020.0024.

The Food and Drug Administration has approved formerly prescription-only Voltaren Arthritis Pain (diclofenac sodium topical gel, 1%) for nonprescription use via a process known as a prescription to over-the-counter (Rx-to-OTC) switch, according to a news release from the agency.

“As a result of the Rx-to-OTC switch process, many products sold over the counter today use ingredients or dosage strengths that were available only by prescription 30 years ago,” Karen Mahoney, MD, acting deputy director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the release.

This switch to nonprescription status is usually initiated by the manufacturer, who must provide data that demonstrates the drug in question is both safe and effective as self-medication in accordance with the proposed labeling and that consumers can use it safely and effectively without the supervision of a health care professional.

This particular therapy is a topical NSAID gel and was first approved by the FDA in 2007 with the indication for relief of osteoarthritis pain. It can take 7 days to have an effect, but if patients find it takes longer than that or they need to use it for more than 21 days, they should seek medical attention. The gel can cause severe allergic reactions, especially in people allergic to aspirin; patients who experience such reactions are advised to stop use and seek immediate medical care. Other concerns include potential for liver damage with extended use; the possibility of severe stomach bleeds; and risk of heart attack, heart failure, and stroke.

The gel will no longer be available in prescription form.

Full prescribing information can be found on the FDA website, as can the full news release regarding this approval.

cpalmer@mdedge.com

The Food and Drug Administration has approved formerly prescription-only Voltaren Arthritis Pain (diclofenac sodium topical gel, 1%) for nonprescription use via a process known as a prescription to over-the-counter (Rx-to-OTC) switch, according to a news release from the agency.

“As a result of the Rx-to-OTC switch process, many products sold over the counter today use ingredients or dosage strengths that were available only by prescription 30 years ago,” Karen Mahoney, MD, acting deputy director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the release.

This switch to nonprescription status is usually initiated by the manufacturer, who must provide data that demonstrates the drug in question is both safe and effective as self-medication in accordance with the proposed labeling and that consumers can use it safely and effectively without the supervision of a health care professional.

This particular therapy is a topical NSAID gel and was first approved by the FDA in 2007 with the indication for relief of osteoarthritis pain. It can take 7 days to have an effect, but if patients find it takes longer than that or they need to use it for more than 21 days, they should seek medical attention. The gel can cause severe allergic reactions, especially in people allergic to aspirin; patients who experience such reactions are advised to stop use and seek immediate medical care. Other concerns include potential for liver damage with extended use; the possibility of severe stomach bleeds; and risk of heart attack, heart failure, and stroke.

The gel will no longer be available in prescription form.

Full prescribing information can be found on the FDA website, as can the full news release regarding this approval.

cpalmer@mdedge.com

The Food and Drug Administration has approved formerly prescription-only Voltaren Arthritis Pain (diclofenac sodium topical gel, 1%) for nonprescription use via a process known as a prescription to over-the-counter (Rx-to-OTC) switch, according to a news release from the agency.

“As a result of the Rx-to-OTC switch process, many products sold over the counter today use ingredients or dosage strengths that were available only by prescription 30 years ago,” Karen Mahoney, MD, acting deputy director of the Office of Nonprescription Drugs in the FDA’s Center for Drug Evaluation and Research, said in the release.

This switch to nonprescription status is usually initiated by the manufacturer, who must provide data that demonstrates the drug in question is both safe and effective as self-medication in accordance with the proposed labeling and that consumers can use it safely and effectively without the supervision of a health care professional.

This particular therapy is a topical NSAID gel and was first approved by the FDA in 2007 with the indication for relief of osteoarthritis pain. It can take 7 days to have an effect, but if patients find it takes longer than that or they need to use it for more than 21 days, they should seek medical attention. The gel can cause severe allergic reactions, especially in people allergic to aspirin; patients who experience such reactions are advised to stop use and seek immediate medical care. Other concerns include potential for liver damage with extended use; the possibility of severe stomach bleeds; and risk of heart attack, heart failure, and stroke.

The gel will no longer be available in prescription form.

Full prescribing information can be found on the FDA website, as can the full news release regarding this approval.

cpalmer@mdedge.com

Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.

Dr. Harris R. Perlman

“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.

Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.

“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).

Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.

In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.

Sharon Worcester/MDedge News

Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
 

Why STB?

Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.

Courtesy Dr. Arthur Mandelin Northwestern University, Chicago

Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.

A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).

A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).

Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.

Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.

“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.

“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.

Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.

In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.

Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.

“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”

The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.

A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.

“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
 

Next steps

These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”

The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).

“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”

In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).

The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.

One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”

In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).

“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.

In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).

Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”

Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.

Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.

“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”

However, Dr. Pitzalis stressed that there remains much work to do.

“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.

Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.

He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”

Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.

“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.

The authors interviewed for this article reported having no relevant financial disclosures.

sworcester@mdedge.com

Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.

Dr. Harris R. Perlman

“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.

Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.

“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).

Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.

In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.

Sharon Worcester/MDedge News

Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
 

Why STB?

Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.

Courtesy Dr. Arthur Mandelin Northwestern University, Chicago

Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.

A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).

A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).

Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.

Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.

“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.

“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.

Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.

In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.

Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.

“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”

The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.

A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.

“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
 

Next steps

These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”

The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).

“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”

In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).

The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.

One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”

In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).

“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.

In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).

Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”

Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.

Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.

“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”

However, Dr. Pitzalis stressed that there remains much work to do.

“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.

Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.

He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”

Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.

“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.

The authors interviewed for this article reported having no relevant financial disclosures.

sworcester@mdedge.com

Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.

Dr. Harris R. Perlman

“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.

Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.

“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).

Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.

In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.

Sharon Worcester/MDedge News

Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
 

Why STB?

Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.

Courtesy Dr. Arthur Mandelin Northwestern University, Chicago

Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.

A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).

A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).

Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.

Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.

“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.

“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.

Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.

In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.

Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.

“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”

The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.

A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.

“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
 

Next steps

These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”

The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).

“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”

In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).

The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.

One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”

In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).

“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.

In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).

Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”

Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.

Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.

“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”

However, Dr. Pitzalis stressed that there remains much work to do.

“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.

Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.

He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”

Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.

“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.

The authors interviewed for this article reported having no relevant financial disclosures.

sworcester@mdedge.com

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Rheumatologists may have a tough time in the office, but they know how to enjoy themselves once the workday ends, according to Medscape’s 2020 Lifestyle, Happiness, & Burnout Report.

In the Medscape survey, less than one-quarter of rheumatologists reported being happy at work, the same as internal medicine, with only neurologists reporting worse at-work happiness rates. While all measured specialties were happier outside of work than at work, no specialty had more of a gap than rheumatologists, rising from 22% at work to 60% outside of work.

The rate of burnout in rheumatologists was slightly higher than that seen in physicians overall (45% vs. 41%), with 78% of rheumatologists reporting that the growing number of bureaucratic tasks contributed most to burnout, followed by increased time devoted to EHRs (43%) and spending too much time at work (40%).

Rheumatologists most commonly dealt with burnout through exercise (46%), isolating themselves from others (45%), and talking with family/friends (44%). Rheumatologists were about average when it came to taking vacation, with 47% taking 3-4 weeks off of work, compared with 44% of all physicians; only 29% took less than 3 weeks’ vacation.

More than 90% of rheumatologists reported that they’d never contemplated suicide, with only 6% reported that they’d thought about it and none reporting that they’d attempted suicide. Similarly, 79% of rheumatologists reported that they are not and do not plan to seek professional help for symptoms of burnout and/or depression, with 10% saying they were currently seeing professional help and 8% saying they had been to therapy but were not anymore.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com

Rheumatologists may have a tough time in the office, but they know how to enjoy themselves once the workday ends, according to Medscape’s 2020 Lifestyle, Happiness, & Burnout Report.

In the Medscape survey, less than one-quarter of rheumatologists reported being happy at work, the same as internal medicine, with only neurologists reporting worse at-work happiness rates. While all measured specialties were happier outside of work than at work, no specialty had more of a gap than rheumatologists, rising from 22% at work to 60% outside of work.

The rate of burnout in rheumatologists was slightly higher than that seen in physicians overall (45% vs. 41%), with 78% of rheumatologists reporting that the growing number of bureaucratic tasks contributed most to burnout, followed by increased time devoted to EHRs (43%) and spending too much time at work (40%).

Rheumatologists most commonly dealt with burnout through exercise (46%), isolating themselves from others (45%), and talking with family/friends (44%). Rheumatologists were about average when it came to taking vacation, with 47% taking 3-4 weeks off of work, compared with 44% of all physicians; only 29% took less than 3 weeks’ vacation.

More than 90% of rheumatologists reported that they’d never contemplated suicide, with only 6% reported that they’d thought about it and none reporting that they’d attempted suicide. Similarly, 79% of rheumatologists reported that they are not and do not plan to seek professional help for symptoms of burnout and/or depression, with 10% saying they were currently seeing professional help and 8% saying they had been to therapy but were not anymore.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com

Rheumatologists may have a tough time in the office, but they know how to enjoy themselves once the workday ends, according to Medscape’s 2020 Lifestyle, Happiness, & Burnout Report.

In the Medscape survey, less than one-quarter of rheumatologists reported being happy at work, the same as internal medicine, with only neurologists reporting worse at-work happiness rates. While all measured specialties were happier outside of work than at work, no specialty had more of a gap than rheumatologists, rising from 22% at work to 60% outside of work.

The rate of burnout in rheumatologists was slightly higher than that seen in physicians overall (45% vs. 41%), with 78% of rheumatologists reporting that the growing number of bureaucratic tasks contributed most to burnout, followed by increased time devoted to EHRs (43%) and spending too much time at work (40%).

Rheumatologists most commonly dealt with burnout through exercise (46%), isolating themselves from others (45%), and talking with family/friends (44%). Rheumatologists were about average when it came to taking vacation, with 47% taking 3-4 weeks off of work, compared with 44% of all physicians; only 29% took less than 3 weeks’ vacation.

More than 90% of rheumatologists reported that they’d never contemplated suicide, with only 6% reported that they’d thought about it and none reporting that they’d attempted suicide. Similarly, 79% of rheumatologists reported that they are not and do not plan to seek professional help for symptoms of burnout and/or depression, with 10% saying they were currently seeing professional help and 8% saying they had been to therapy but were not anymore.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

lfranki@mdedge.com