Health care experts have long known of a link between patient outcomes and a hospital’s organizational culture, according to an article in the New York Times by Pauline W. Chen, MD.

“Heart attack patients who are treated at hospitals where nurses feel powerless and senior management is only sporadically involved in patient care tend to fare more poorly than patients hospitalized at institutions where nurses are asked regularly for their input and chief executives hold regular meetings with clinicians to review patient results,” she wrote.

But there is hope for change, Dr. Chen noted, and it’s demonstrable, citing a group of researchers that has written about strategies targeting hospital organizational culture called “Leadership Saves Lives.” The researchers showed hospitals could create significant cultural changes, which could impact patient outcomes, in just 2 years.

“Leadership Saves Lives requires that each hospital create a ‘Guiding Coalition,’ a group of staff members from across the entire institution. The coalition members participate in regular workshops, discussions, and national forums on ways hospitals might improve, then help their respective hospital translate newfound ideas and information into clinical practice,” she wrote.

The researchers monitored heart attack patients to assess the effect of Leadership Saves Lives in 10 hospitals that had below average patient outcomes. Over 2 years, all 10 hospitals changed significantly, but 6 hospitals experienced particularly profound cultural transformations.

“The staff of these hospitals spoke of an institutional shift from ‘because I said so’ to ‘focusing on the why’s,’ ” Dr. Chen wrote. “Instead of accepting that every heart attack patient had to undergo certain testing or take specific drugs because the chief of the department or administrator had previously established such clinical protocols, for example, it became more important to provide the data that proved such rituals were actually helpful. Staff members in these hospitals also said they received, and appreciated, increased support from senior management and a newfound freedom to voice opinions in ‘more of an equal role, no matter what position you are.’ ”

The degree of an institution’s cultural change was directly linked to patient outcomes, the researchers found. Indeed, hospitals that made more substantial changes in their work culture realized larger and more sustained drops in heart attack mortality rates.

References

1. Chen PW. A More Egalitarian Hospital Culture Is Better for Everyone. New York Times. https://www.nytimes.com/2018/05/31/well/live/doctors-patients-hospital-culture-better-health.html. Published May 31, 2018. Accessed June 1, 2018.

2. Curry LA et al. Organizational culture change in U.S. hospitals: A mixed methods longitudinal intervention study. Implementation Science. 2015 Mar 7. doi: 10.1186/s13012-015-0218-0. Accessed June 18, 2018.

Health care experts have long known of a link between patient outcomes and a hospital’s organizational culture, according to an article in the New York Times by Pauline W. Chen, MD.

“Heart attack patients who are treated at hospitals where nurses feel powerless and senior management is only sporadically involved in patient care tend to fare more poorly than patients hospitalized at institutions where nurses are asked regularly for their input and chief executives hold regular meetings with clinicians to review patient results,” she wrote.

But there is hope for change, Dr. Chen noted, and it’s demonstrable, citing a group of researchers that has written about strategies targeting hospital organizational culture called “Leadership Saves Lives.” The researchers showed hospitals could create significant cultural changes, which could impact patient outcomes, in just 2 years.

“Leadership Saves Lives requires that each hospital create a ‘Guiding Coalition,’ a group of staff members from across the entire institution. The coalition members participate in regular workshops, discussions, and national forums on ways hospitals might improve, then help their respective hospital translate newfound ideas and information into clinical practice,” she wrote.

The researchers monitored heart attack patients to assess the effect of Leadership Saves Lives in 10 hospitals that had below average patient outcomes. Over 2 years, all 10 hospitals changed significantly, but 6 hospitals experienced particularly profound cultural transformations.

“The staff of these hospitals spoke of an institutional shift from ‘because I said so’ to ‘focusing on the why’s,’ ” Dr. Chen wrote. “Instead of accepting that every heart attack patient had to undergo certain testing or take specific drugs because the chief of the department or administrator had previously established such clinical protocols, for example, it became more important to provide the data that proved such rituals were actually helpful. Staff members in these hospitals also said they received, and appreciated, increased support from senior management and a newfound freedom to voice opinions in ‘more of an equal role, no matter what position you are.’ ”

The degree of an institution’s cultural change was directly linked to patient outcomes, the researchers found. Indeed, hospitals that made more substantial changes in their work culture realized larger and more sustained drops in heart attack mortality rates.

References

1. Chen PW. A More Egalitarian Hospital Culture Is Better for Everyone. New York Times. https://www.nytimes.com/2018/05/31/well/live/doctors-patients-hospital-culture-better-health.html. Published May 31, 2018. Accessed June 1, 2018.

2. Curry LA et al. Organizational culture change in U.S. hospitals: A mixed methods longitudinal intervention study. Implementation Science. 2015 Mar 7. doi: 10.1186/s13012-015-0218-0. Accessed June 18, 2018.

Health care experts have long known of a link between patient outcomes and a hospital’s organizational culture, according to an article in the New York Times by Pauline W. Chen, MD.

“Heart attack patients who are treated at hospitals where nurses feel powerless and senior management is only sporadically involved in patient care tend to fare more poorly than patients hospitalized at institutions where nurses are asked regularly for their input and chief executives hold regular meetings with clinicians to review patient results,” she wrote.

But there is hope for change, Dr. Chen noted, and it’s demonstrable, citing a group of researchers that has written about strategies targeting hospital organizational culture called “Leadership Saves Lives.” The researchers showed hospitals could create significant cultural changes, which could impact patient outcomes, in just 2 years.

“Leadership Saves Lives requires that each hospital create a ‘Guiding Coalition,’ a group of staff members from across the entire institution. The coalition members participate in regular workshops, discussions, and national forums on ways hospitals might improve, then help their respective hospital translate newfound ideas and information into clinical practice,” she wrote.

The researchers monitored heart attack patients to assess the effect of Leadership Saves Lives in 10 hospitals that had below average patient outcomes. Over 2 years, all 10 hospitals changed significantly, but 6 hospitals experienced particularly profound cultural transformations.

“The staff of these hospitals spoke of an institutional shift from ‘because I said so’ to ‘focusing on the why’s,’ ” Dr. Chen wrote. “Instead of accepting that every heart attack patient had to undergo certain testing or take specific drugs because the chief of the department or administrator had previously established such clinical protocols, for example, it became more important to provide the data that proved such rituals were actually helpful. Staff members in these hospitals also said they received, and appreciated, increased support from senior management and a newfound freedom to voice opinions in ‘more of an equal role, no matter what position you are.’ ”

The degree of an institution’s cultural change was directly linked to patient outcomes, the researchers found. Indeed, hospitals that made more substantial changes in their work culture realized larger and more sustained drops in heart attack mortality rates.

References

1. Chen PW. A More Egalitarian Hospital Culture Is Better for Everyone. New York Times. https://www.nytimes.com/2018/05/31/well/live/doctors-patients-hospital-culture-better-health.html. Published May 31, 2018. Accessed June 1, 2018.

2. Curry LA et al. Organizational culture change in U.S. hospitals: A mixed methods longitudinal intervention study. Implementation Science. 2015 Mar 7. doi: 10.1186/s13012-015-0218-0. Accessed June 18, 2018.

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

What does your patient need to know at the first visit?

Patient education is important initially. There are several causes for nail dystrophy. Oftentimes, when patients present, they believe that they have onychomycosis. Therefore, it is important to counsel individuals with potential nail psoriasis (Figure) and to discuss the differential diagnosis of the condition.

The presence of psoriasis on other areas of the body and the absence of fungal infection on the soles of the feet and in between the toes increases the likelihood of nail psoriasis. The most accurate test to perform is a nail clipping with subsequent periodic acid–Schiff stain. It is important to remember, however, that nail psoriasis and fungal infection of the nail can coexist.

Once the diagnosis of nail psoriasis is established, it is important to review gentle care of the nails. A thorough discussion of therapeutic options is helpful. Patients also should be advised that the presence of nail psoriasis can increase the likelihood of the development of
psoriatic arthritis.

What are your go-to treatments?

Prior to the development of biologic therapies, topical treatments were the mainstay of treatment. Topical corticosteroid preparations can be used around and under the nail. Other therapeutic options include topical calcipotriene and topical retinoids.

Intralesional injection is another therapeutic option. Injection into the nail bed is useful for the treatment of nail bed symptoms of nail psoriasis such as onycholysis. Injection into the proximal nail fold can ameliorate signs of nail matrix psoriasis such as nail pitting. Although injection can be effective, it also can be painful; therefore, many patients do not opt to have this therapy performed.

Systemic therapy has been shown to be highly effective in improving nail psoriasis. There has been a good amount of data from studies specifically done in nail psoriasis and nail data that have been taken from larger phase 3 trials (Elewski et al; van de Kerkhof et al). Therefore, several of the biologics on the market as well apremilast are good options for the treatment of nail psoriasis. When using a systemic agent, it is important to carefully review the benefits and risks of each therapy with patients. Because the nail grows slowly, improvement can be gradual and take several months to peak.

How do you keep patients compliant with treatment?

Because nail psoriasis causes distress among patients, it generally is not too hard for them to be compliant. Of course, it is important to have regular follow-up to monitor progress and to reinforce the importance of continued therapy. At the end of the day, however, treatment success is the best asset to encourage continued compliance.

Resources for Patients
Managing nail psoriasis
http://www.psoriasis.org/about-psoriasis/specific-locations/hands-feet-nails/managing-nail-psoriasis

What is nail psoriasis, and how can I treat it?
http://www.aad.org/public/diseases/scaly-skin/psoriasis/diagnosis-and-treatment-of-psoriasis/what-is-nail-psoriasis-and-how-can-i-treat-it

Suggested Readings
Elewski BE, Okun MM, Papp K, et al. Adalimumab for nail psoriasis: efficacy and safety from the first 26 weeks of phase 3, randomized, placebo controlled trial. J Am Acad Dermatol. 2018;78:90.e1-99.e1.

Van de Kerkhof P, Guenther L, Gottlieb AB, et al. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled, and open-label phases of UNCOVER-3. J Eur Acad Dermatol Venereol. 2017;31:477-482.

Yin N, Choudhary S, Nouri K. Pulsed dye laser for the treatment of nail psoriasis. Cutis. 2013;92:129-135.

What does your patient need to know at the first visit?

Patient education is important initially. There are several causes for nail dystrophy. Oftentimes, when patients present, they believe that they have onychomycosis. Therefore, it is important to counsel individuals with potential nail psoriasis (Figure) and to discuss the differential diagnosis of the condition.

The presence of psoriasis on other areas of the body and the absence of fungal infection on the soles of the feet and in between the toes increases the likelihood of nail psoriasis. The most accurate test to perform is a nail clipping with subsequent periodic acid–Schiff stain. It is important to remember, however, that nail psoriasis and fungal infection of the nail can coexist.

Once the diagnosis of nail psoriasis is established, it is important to review gentle care of the nails. A thorough discussion of therapeutic options is helpful. Patients also should be advised that the presence of nail psoriasis can increase the likelihood of the development of
psoriatic arthritis.

What are your go-to treatments?

Prior to the development of biologic therapies, topical treatments were the mainstay of treatment. Topical corticosteroid preparations can be used around and under the nail. Other therapeutic options include topical calcipotriene and topical retinoids.

Intralesional injection is another therapeutic option. Injection into the nail bed is useful for the treatment of nail bed symptoms of nail psoriasis such as onycholysis. Injection into the proximal nail fold can ameliorate signs of nail matrix psoriasis such as nail pitting. Although injection can be effective, it also can be painful; therefore, many patients do not opt to have this therapy performed.

Systemic therapy has been shown to be highly effective in improving nail psoriasis. There has been a good amount of data from studies specifically done in nail psoriasis and nail data that have been taken from larger phase 3 trials (Elewski et al; van de Kerkhof et al). Therefore, several of the biologics on the market as well apremilast are good options for the treatment of nail psoriasis. When using a systemic agent, it is important to carefully review the benefits and risks of each therapy with patients. Because the nail grows slowly, improvement can be gradual and take several months to peak.

How do you keep patients compliant with treatment?

Because nail psoriasis causes distress among patients, it generally is not too hard for them to be compliant. Of course, it is important to have regular follow-up to monitor progress and to reinforce the importance of continued therapy. At the end of the day, however, treatment success is the best asset to encourage continued compliance.

Resources for Patients
Managing nail psoriasis
http://www.psoriasis.org/about-psoriasis/specific-locations/hands-feet-nails/managing-nail-psoriasis

What is nail psoriasis, and how can I treat it?
http://www.aad.org/public/diseases/scaly-skin/psoriasis/diagnosis-and-treatment-of-psoriasis/what-is-nail-psoriasis-and-how-can-i-treat-it

Suggested Readings
Elewski BE, Okun MM, Papp K, et al. Adalimumab for nail psoriasis: efficacy and safety from the first 26 weeks of phase 3, randomized, placebo controlled trial. J Am Acad Dermatol. 2018;78:90.e1-99.e1.

Van de Kerkhof P, Guenther L, Gottlieb AB, et al. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled, and open-label phases of UNCOVER-3. J Eur Acad Dermatol Venereol. 2017;31:477-482.

Yin N, Choudhary S, Nouri K. Pulsed dye laser for the treatment of nail psoriasis. Cutis. 2013;92:129-135.

What does your patient need to know at the first visit?

Patient education is important initially. There are several causes for nail dystrophy. Oftentimes, when patients present, they believe that they have onychomycosis. Therefore, it is important to counsel individuals with potential nail psoriasis (Figure) and to discuss the differential diagnosis of the condition.

The presence of psoriasis on other areas of the body and the absence of fungal infection on the soles of the feet and in between the toes increases the likelihood of nail psoriasis. The most accurate test to perform is a nail clipping with subsequent periodic acid–Schiff stain. It is important to remember, however, that nail psoriasis and fungal infection of the nail can coexist.

Once the diagnosis of nail psoriasis is established, it is important to review gentle care of the nails. A thorough discussion of therapeutic options is helpful. Patients also should be advised that the presence of nail psoriasis can increase the likelihood of the development of
psoriatic arthritis.

What are your go-to treatments?

Prior to the development of biologic therapies, topical treatments were the mainstay of treatment. Topical corticosteroid preparations can be used around and under the nail. Other therapeutic options include topical calcipotriene and topical retinoids.

Intralesional injection is another therapeutic option. Injection into the nail bed is useful for the treatment of nail bed symptoms of nail psoriasis such as onycholysis. Injection into the proximal nail fold can ameliorate signs of nail matrix psoriasis such as nail pitting. Although injection can be effective, it also can be painful; therefore, many patients do not opt to have this therapy performed.

Systemic therapy has been shown to be highly effective in improving nail psoriasis. There has been a good amount of data from studies specifically done in nail psoriasis and nail data that have been taken from larger phase 3 trials (Elewski et al; van de Kerkhof et al). Therefore, several of the biologics on the market as well apremilast are good options for the treatment of nail psoriasis. When using a systemic agent, it is important to carefully review the benefits and risks of each therapy with patients. Because the nail grows slowly, improvement can be gradual and take several months to peak.

How do you keep patients compliant with treatment?

Because nail psoriasis causes distress among patients, it generally is not too hard for them to be compliant. Of course, it is important to have regular follow-up to monitor progress and to reinforce the importance of continued therapy. At the end of the day, however, treatment success is the best asset to encourage continued compliance.

Resources for Patients
Managing nail psoriasis
http://www.psoriasis.org/about-psoriasis/specific-locations/hands-feet-nails/managing-nail-psoriasis

What is nail psoriasis, and how can I treat it?
http://www.aad.org/public/diseases/scaly-skin/psoriasis/diagnosis-and-treatment-of-psoriasis/what-is-nail-psoriasis-and-how-can-i-treat-it

Suggested Readings
Elewski BE, Okun MM, Papp K, et al. Adalimumab for nail psoriasis: efficacy and safety from the first 26 weeks of phase 3, randomized, placebo controlled trial. J Am Acad Dermatol. 2018;78:90.e1-99.e1.

Van de Kerkhof P, Guenther L, Gottlieb AB, et al. Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled, and open-label phases of UNCOVER-3. J Eur Acad Dermatol Venereol. 2017;31:477-482.

Yin N, Choudhary S, Nouri K. Pulsed dye laser for the treatment of nail psoriasis. Cutis. 2013;92:129-135.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

Granuloma annulare (GA) is a granulomatous skin disorder of uncertain etiology. A number of clinical variants exist, most commonly localized annular plaques on the hands or feet, generalized lesions, or subcutaneous nodules in children. Histologically, GA exhibits granulomatous inflammation with either interstitial or palisading lymphocytes and histiocytes with mucin deposition.

Few data exist regarding the epidemiology of GA. Although the pathogenesis of GA is unknown, associations between GA and underlying systemic processes, such as diabetes mellitus, hyperlipidemia, thyroid disease, and human immunodeficiency virus (HIV), have been suggested.

The purpose of this retrospective study was to determine the number of cases of GA seen annually at the Department of Dermatology at the University of Pennsylvania (Philadelphia, Pennsylvania) from 2008 to 2014. Additionally, we reviewed all cases of biopsy-proven GA from 2010 to 2014 and reported the demographics, underlying medical comorbidities, medications, treatments, and outcomes seen in this patient population.

Methods

We identified the number of outpatients presenting with GA annually using PennSeek, a tool developed by the Penn Medicine Data Analytics Center to search electronic medical records (EMRs). We queried the EMR database to determine the number of discrete patients seen at the Department of Dermatology at the University of Pennsylvania annually from 2008 (the year the EMR was established) to 2014. We then used PennSeek to determine the number of patients given a diagnosis of GA annually from 2008 to 2014 based on the International Classification of Diseases, Ninth Revision (ICD-9).

After using PennSeek to identify all patients given the ICD-9 diagnosis of GA from 2008 to 2014, we reviewed the EMRs of these patients to identify cases that were biopsy proven. For the biopsy-proven cases of GA seen at the University of Pennsylvania from 2010 to 2014, we reviewed the EMRs of these patients for clinical characteristics and treatment outcomes. For each case, we recorded the patient’s age, sex, medical comorbidities, GA subtype, and medications.

This study was approved by the University of Pennsylvania’s institutional review board.

Results

On average, the percentage of patients given a diagnosis of GA annually was 0.22% (95% CI, 0.19%-0.24%). A Pearson χ² test was used to determine if any single annual percentage was significantly different from the others. We found a P value of .321, which suggests that the percentage of patients with GA seen annually has been stable from 2008 to 2014 (Figure).

There were 133 cases of biopsy-proven GA that were reviewed for clinical characteristics; of them, 86.5% were female. Thyroid disease was noted in 30.1% of patients, hyperlipidemia in 30.1%, and hematologic malignancies in 3.8%. Type 1 diabetes mellitus was noted in 1.5% of patients. None of the patients were HIV-positive, 1.5% were hepatitis B–positive, and 2.3% were hepatitis C–positive. Of the 133 cases, 64.7% had localized GA and 30.8% had generalized GA. Photosensitive and papular GA were rarer (1.5% and 2.3% of cases, respectively). Use of a selective serotonin reuptake inhibitor (SSRI) was noted in 18.1% of patients; use of a calcium channel blocker was noted in 9.0% (Table 1).

Comment

We attempted to determine the period of prevalence of GA in a tertiary care, university-based referral practice and evaluate disease associations, treatments, and outcomes of patients with biopsy-proven GA. Our calculated period prevalence of GA of 0.22% to 0.27% is consistent with another review, which reported that 0.1% to 0.4% of new patients presenting to a dermatology practice were given a diagnosis of GA.¹ More than 85% of the cases we reviewed were seen in females, a finding that is more heavily skewed compared to prior reports that have suggested a female to male ratio of approximately 1:1 to 2:1.^1-7 Our findings suggest that GA is a female-predominant condition, or women may be more likely to seek evaluation for the condition.

More than 95% of the cases we reviewed were localized (64.7%) or generalized (30.8%) GA, making these variants the most common forms of GA, which is consistent with prior reports.^1-3,8,9 Other varieties of GA—drug induced, patch, perforating, photosensitive, palmar, and papular—appear rare. Because this study was conducted at an adult hospital, subcutaneous GA, which often is seen in children, may be underrepresented. As a retrospective chart review, it is possible that documentation is insufficient to capture each rare variant.

At 1.5%, the prevalence of type 1 diabetes mellitus in our patients is slightly higher than the national average of 0.3%.²⁵ However, based on a Fisher exact test of analysis of proportions, this difference is not statistically significant (P=.106).

At 1.5% and 2.3%, the prevalence of hepatitis B and hepatitis C, respectively, in our patients is slightly higher than the national average of 0.5% and 1%, respectively.²⁶ However, based on a Fisher exact test of analysis of proportions, these differences are not statistically significant (P=.142 and P=.146, respectively).

Given the high prevalence of hyperlipidemia in the United States (31.7%), this disease is not overrepresented in our sample (30.1%), though others have suggested there may be a connection.^27,28 Based on a Fisher exact test, this difference of proportions is not statistically significant (P=.780).

Selective serotonin reuptake inhibitor use is common in the United States; approximately 11% of Americans older than 12 years use an SSRI.²⁹ At 18.1%, the use of SSRIs in our patient group was statistically significantly higher than the national average (Fisher exact test, P=.017), suggesting a possible association between SSRI use and development of GA, warranting further investigation.

The use of calcium channel blockers, interferon, and tumor necrosis factor inhibitors was not significantly associated with GA in our series.

GA Therapy
The most commonly used treatments for GA in our study were topical steroids and intralesional triamcinolone, followed by hydroxychloroquine; all treatments employed exhibited a widely variable response. Assessing treatment response via retrospective chart review is challenging and response rates may not be accurately captured.

Study Limitations
Our study had several limitations. In calculating the period prevalence of GA, our query was limited by the number of years that the EMR has been in place. The number of cases we reviewed for clinical characteristics was limited to 133, as many cases with the ICD-9 diagnosis of GA were not biopsy proven and therefore were not included in our review. Many of the cases we reviewed were lost to follow-up, which prevented us from determining treatment outcomes.

Another weakness of our study was that our query did not provide an estimate of incidence or prevalence of GA overall, as this analysis was not a population-based study. The power of our study was limited by the number of cases of GA seen annually and the number of patients lost to follow-up. Additionally, our study population may only be generalizable to other large academic centers.

Conclusion

This study further solidifies our understanding of the epidemiology of GA and diseases that can be associated with GA. We identified a higher female to male ratio than previous reports, and consistent with prior reports, we noted potential associations with conditions such as thyroid disease and hyperlipidemia. Our population demonstrated higher rates of SSRI use than expected, warranting further investigation. Dermatologists should be aware of potential disease associations with GA, but as a whole we need better data and larger studies to determine the appropriate evaluation and treatment for patients with GA.

Granuloma annulare (GA) is a granulomatous skin disorder of uncertain etiology. A number of clinical variants exist, most commonly localized annular plaques on the hands or feet, generalized lesions, or subcutaneous nodules in children. Histologically, GA exhibits granulomatous inflammation with either interstitial or palisading lymphocytes and histiocytes with mucin deposition.

Few data exist regarding the epidemiology of GA. Although the pathogenesis of GA is unknown, associations between GA and underlying systemic processes, such as diabetes mellitus, hyperlipidemia, thyroid disease, and human immunodeficiency virus (HIV), have been suggested.

The purpose of this retrospective study was to determine the number of cases of GA seen annually at the Department of Dermatology at the University of Pennsylvania (Philadelphia, Pennsylvania) from 2008 to 2014. Additionally, we reviewed all cases of biopsy-proven GA from 2010 to 2014 and reported the demographics, underlying medical comorbidities, medications, treatments, and outcomes seen in this patient population.

Methods

We identified the number of outpatients presenting with GA annually using PennSeek, a tool developed by the Penn Medicine Data Analytics Center to search electronic medical records (EMRs). We queried the EMR database to determine the number of discrete patients seen at the Department of Dermatology at the University of Pennsylvania annually from 2008 (the year the EMR was established) to 2014. We then used PennSeek to determine the number of patients given a diagnosis of GA annually from 2008 to 2014 based on the International Classification of Diseases, Ninth Revision (ICD-9).

After using PennSeek to identify all patients given the ICD-9 diagnosis of GA from 2008 to 2014, we reviewed the EMRs of these patients to identify cases that were biopsy proven. For the biopsy-proven cases of GA seen at the University of Pennsylvania from 2010 to 2014, we reviewed the EMRs of these patients for clinical characteristics and treatment outcomes. For each case, we recorded the patient’s age, sex, medical comorbidities, GA subtype, and medications.

This study was approved by the University of Pennsylvania’s institutional review board.

Results

On average, the percentage of patients given a diagnosis of GA annually was 0.22% (95% CI, 0.19%-0.24%). A Pearson χ² test was used to determine if any single annual percentage was significantly different from the others. We found a P value of .321, which suggests that the percentage of patients with GA seen annually has been stable from 2008 to 2014 (Figure).

There were 133 cases of biopsy-proven GA that were reviewed for clinical characteristics; of them, 86.5% were female. Thyroid disease was noted in 30.1% of patients, hyperlipidemia in 30.1%, and hematologic malignancies in 3.8%. Type 1 diabetes mellitus was noted in 1.5% of patients. None of the patients were HIV-positive, 1.5% were hepatitis B–positive, and 2.3% were hepatitis C–positive. Of the 133 cases, 64.7% had localized GA and 30.8% had generalized GA. Photosensitive and papular GA were rarer (1.5% and 2.3% of cases, respectively). Use of a selective serotonin reuptake inhibitor (SSRI) was noted in 18.1% of patients; use of a calcium channel blocker was noted in 9.0% (Table 1).

Comment

We attempted to determine the period of prevalence of GA in a tertiary care, university-based referral practice and evaluate disease associations, treatments, and outcomes of patients with biopsy-proven GA. Our calculated period prevalence of GA of 0.22% to 0.27% is consistent with another review, which reported that 0.1% to 0.4% of new patients presenting to a dermatology practice were given a diagnosis of GA.¹ More than 85% of the cases we reviewed were seen in females, a finding that is more heavily skewed compared to prior reports that have suggested a female to male ratio of approximately 1:1 to 2:1.^1-7 Our findings suggest that GA is a female-predominant condition, or women may be more likely to seek evaluation for the condition.

More than 95% of the cases we reviewed were localized (64.7%) or generalized (30.8%) GA, making these variants the most common forms of GA, which is consistent with prior reports.^1-3,8,9 Other varieties of GA—drug induced, patch, perforating, photosensitive, palmar, and papular—appear rare. Because this study was conducted at an adult hospital, subcutaneous GA, which often is seen in children, may be underrepresented. As a retrospective chart review, it is possible that documentation is insufficient to capture each rare variant.

At 1.5%, the prevalence of type 1 diabetes mellitus in our patients is slightly higher than the national average of 0.3%.²⁵ However, based on a Fisher exact test of analysis of proportions, this difference is not statistically significant (P=.106).

At 1.5% and 2.3%, the prevalence of hepatitis B and hepatitis C, respectively, in our patients is slightly higher than the national average of 0.5% and 1%, respectively.²⁶ However, based on a Fisher exact test of analysis of proportions, these differences are not statistically significant (P=.142 and P=.146, respectively).

Given the high prevalence of hyperlipidemia in the United States (31.7%), this disease is not overrepresented in our sample (30.1%), though others have suggested there may be a connection.^27,28 Based on a Fisher exact test, this difference of proportions is not statistically significant (P=.780).

Selective serotonin reuptake inhibitor use is common in the United States; approximately 11% of Americans older than 12 years use an SSRI.²⁹ At 18.1%, the use of SSRIs in our patient group was statistically significantly higher than the national average (Fisher exact test, P=.017), suggesting a possible association between SSRI use and development of GA, warranting further investigation.

The use of calcium channel blockers, interferon, and tumor necrosis factor inhibitors was not significantly associated with GA in our series.

GA Therapy
The most commonly used treatments for GA in our study were topical steroids and intralesional triamcinolone, followed by hydroxychloroquine; all treatments employed exhibited a widely variable response. Assessing treatment response via retrospective chart review is challenging and response rates may not be accurately captured.

Study Limitations
Our study had several limitations. In calculating the period prevalence of GA, our query was limited by the number of years that the EMR has been in place. The number of cases we reviewed for clinical characteristics was limited to 133, as many cases with the ICD-9 diagnosis of GA were not biopsy proven and therefore were not included in our review. Many of the cases we reviewed were lost to follow-up, which prevented us from determining treatment outcomes.

Another weakness of our study was that our query did not provide an estimate of incidence or prevalence of GA overall, as this analysis was not a population-based study. The power of our study was limited by the number of cases of GA seen annually and the number of patients lost to follow-up. Additionally, our study population may only be generalizable to other large academic centers.

Conclusion

This study further solidifies our understanding of the epidemiology of GA and diseases that can be associated with GA. We identified a higher female to male ratio than previous reports, and consistent with prior reports, we noted potential associations with conditions such as thyroid disease and hyperlipidemia. Our population demonstrated higher rates of SSRI use than expected, warranting further investigation. Dermatologists should be aware of potential disease associations with GA, but as a whole we need better data and larger studies to determine the appropriate evaluation and treatment for patients with GA.

Granuloma annulare (GA) is a granulomatous skin disorder of uncertain etiology. A number of clinical variants exist, most commonly localized annular plaques on the hands or feet, generalized lesions, or subcutaneous nodules in children. Histologically, GA exhibits granulomatous inflammation with either interstitial or palisading lymphocytes and histiocytes with mucin deposition.

Few data exist regarding the epidemiology of GA. Although the pathogenesis of GA is unknown, associations between GA and underlying systemic processes, such as diabetes mellitus, hyperlipidemia, thyroid disease, and human immunodeficiency virus (HIV), have been suggested.

The purpose of this retrospective study was to determine the number of cases of GA seen annually at the Department of Dermatology at the University of Pennsylvania (Philadelphia, Pennsylvania) from 2008 to 2014. Additionally, we reviewed all cases of biopsy-proven GA from 2010 to 2014 and reported the demographics, underlying medical comorbidities, medications, treatments, and outcomes seen in this patient population.

Methods

We identified the number of outpatients presenting with GA annually using PennSeek, a tool developed by the Penn Medicine Data Analytics Center to search electronic medical records (EMRs). We queried the EMR database to determine the number of discrete patients seen at the Department of Dermatology at the University of Pennsylvania annually from 2008 (the year the EMR was established) to 2014. We then used PennSeek to determine the number of patients given a diagnosis of GA annually from 2008 to 2014 based on the International Classification of Diseases, Ninth Revision (ICD-9).

After using PennSeek to identify all patients given the ICD-9 diagnosis of GA from 2008 to 2014, we reviewed the EMRs of these patients to identify cases that were biopsy proven. For the biopsy-proven cases of GA seen at the University of Pennsylvania from 2010 to 2014, we reviewed the EMRs of these patients for clinical characteristics and treatment outcomes. For each case, we recorded the patient’s age, sex, medical comorbidities, GA subtype, and medications.

This study was approved by the University of Pennsylvania’s institutional review board.

Results

On average, the percentage of patients given a diagnosis of GA annually was 0.22% (95% CI, 0.19%-0.24%). A Pearson χ² test was used to determine if any single annual percentage was significantly different from the others. We found a P value of .321, which suggests that the percentage of patients with GA seen annually has been stable from 2008 to 2014 (Figure).

There were 133 cases of biopsy-proven GA that were reviewed for clinical characteristics; of them, 86.5% were female. Thyroid disease was noted in 30.1% of patients, hyperlipidemia in 30.1%, and hematologic malignancies in 3.8%. Type 1 diabetes mellitus was noted in 1.5% of patients. None of the patients were HIV-positive, 1.5% were hepatitis B–positive, and 2.3% were hepatitis C–positive. Of the 133 cases, 64.7% had localized GA and 30.8% had generalized GA. Photosensitive and papular GA were rarer (1.5% and 2.3% of cases, respectively). Use of a selective serotonin reuptake inhibitor (SSRI) was noted in 18.1% of patients; use of a calcium channel blocker was noted in 9.0% (Table 1).

Comment

We attempted to determine the period of prevalence of GA in a tertiary care, university-based referral practice and evaluate disease associations, treatments, and outcomes of patients with biopsy-proven GA. Our calculated period prevalence of GA of 0.22% to 0.27% is consistent with another review, which reported that 0.1% to 0.4% of new patients presenting to a dermatology practice were given a diagnosis of GA.¹ More than 85% of the cases we reviewed were seen in females, a finding that is more heavily skewed compared to prior reports that have suggested a female to male ratio of approximately 1:1 to 2:1.^1-7 Our findings suggest that GA is a female-predominant condition, or women may be more likely to seek evaluation for the condition.

More than 95% of the cases we reviewed were localized (64.7%) or generalized (30.8%) GA, making these variants the most common forms of GA, which is consistent with prior reports.^1-3,8,9 Other varieties of GA—drug induced, patch, perforating, photosensitive, palmar, and papular—appear rare. Because this study was conducted at an adult hospital, subcutaneous GA, which often is seen in children, may be underrepresented. As a retrospective chart review, it is possible that documentation is insufficient to capture each rare variant.

At 1.5%, the prevalence of type 1 diabetes mellitus in our patients is slightly higher than the national average of 0.3%.²⁵ However, based on a Fisher exact test of analysis of proportions, this difference is not statistically significant (P=.106).

At 1.5% and 2.3%, the prevalence of hepatitis B and hepatitis C, respectively, in our patients is slightly higher than the national average of 0.5% and 1%, respectively.²⁶ However, based on a Fisher exact test of analysis of proportions, these differences are not statistically significant (P=.142 and P=.146, respectively).

Given the high prevalence of hyperlipidemia in the United States (31.7%), this disease is not overrepresented in our sample (30.1%), though others have suggested there may be a connection.^27,28 Based on a Fisher exact test, this difference of proportions is not statistically significant (P=.780).

Selective serotonin reuptake inhibitor use is common in the United States; approximately 11% of Americans older than 12 years use an SSRI.²⁹ At 18.1%, the use of SSRIs in our patient group was statistically significantly higher than the national average (Fisher exact test, P=.017), suggesting a possible association between SSRI use and development of GA, warranting further investigation.

The use of calcium channel blockers, interferon, and tumor necrosis factor inhibitors was not significantly associated with GA in our series.

GA Therapy
The most commonly used treatments for GA in our study were topical steroids and intralesional triamcinolone, followed by hydroxychloroquine; all treatments employed exhibited a widely variable response. Assessing treatment response via retrospective chart review is challenging and response rates may not be accurately captured.

Study Limitations
Our study had several limitations. In calculating the period prevalence of GA, our query was limited by the number of years that the EMR has been in place. The number of cases we reviewed for clinical characteristics was limited to 133, as many cases with the ICD-9 diagnosis of GA were not biopsy proven and therefore were not included in our review. Many of the cases we reviewed were lost to follow-up, which prevented us from determining treatment outcomes.

Another weakness of our study was that our query did not provide an estimate of incidence or prevalence of GA overall, as this analysis was not a population-based study. The power of our study was limited by the number of cases of GA seen annually and the number of patients lost to follow-up. Additionally, our study population may only be generalizable to other large academic centers.

Conclusion

This study further solidifies our understanding of the epidemiology of GA and diseases that can be associated with GA. We identified a higher female to male ratio than previous reports, and consistent with prior reports, we noted potential associations with conditions such as thyroid disease and hyperlipidemia. Our population demonstrated higher rates of SSRI use than expected, warranting further investigation. Dermatologists should be aware of potential disease associations with GA, but as a whole we need better data and larger studies to determine the appropriate evaluation and treatment for patients with GA.

WASHINGTON – Oncologists and cardiologists need to work hand-in-hand when managing the care of women with breast cancer whose treatment plan includes cardiotoxic therapies and breast irradiation, reported specialists.

Neil Osterweil/MDedge News

Depending on the cancer subtype, women with breast cancer may receive chemotherapy with a cardiotoxic anthracycline such as doxorubicin or epirubicin, or a HER2-targeted agent such as trastuzumab (Herceptin), pertuzumab (Perjeta), or ado-trastuzumab emtansine (Kadcyla).

“The cardiotoxicity related to breast cancer has been a well publicized issue, and chances are your patients know about it and are concerned as well,” Jennifer E. Liu, MD, director of cardiovascular laboratories at Memorial Sloan Kettering Cancer Center in New York, said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Anthracyclines, trastuzumab, and HF

In large adjuvant therapy trials of anthracyclines and trastuzumab in women with breast cancer, doxorubicin alone was associated with an asymptomatic decline in left ventricular ejection fraction (LVEF) of 4% to 11%, and a less than 1% incidence of heart failure (HF), Dr. Liu noted.

When patients received an anthracycline followed by trastuzumab, the incidence of asymptomatic LVEF decline ranged from 4% to 19%, the incidence of clinical HF was 2% to 4%, and the rate of trastuzumab interruption for cardiac adverse events ranged from 5% to 18%.

In comparison, in trials with trastuzumab in combination therapy that did not contain an anthracycline, the risk of cardiovascular complications was lower, with asymptomatic decline in LVEF ranging from 3.2% to 9.4%, and class III/IV HF occurring in just 0.5% of patients. In trials combining trastuzumab and pertuzumab, there were no increases in cardiac toxicity over trastuzumab alone.

Although with longer follow-up, the approximately 4% rate of HF in patients treated with anthracycline-based chemotherapy, paclitaxel, and trastuzumab in the NSABP B-31 trial has not changed significantly; retrospective claims-based studies reflecting daily practice have shown significantly higher rates of HF and or cardiomyopathy, Dr. Liu said.

She cited a 2012 study showing that among 45,537 women with a mean age of 76 years who were treated for breast cancer, the 3-year incidence rates of HF and/or cardiomyopathy were 32% for patients treated with trastuzumab alone, and 41.9% for those treated with an anthracycline followed by trastuzumab. Other, smaller studies also showed lower but significantly elevated risks for the drugs.

The discrepancy between clinical trial and “real world” results may be chalked up to the fact that claims-based data rely on diagnostic codes that may not accurately reflect the actual cardiac diagnosis, and by the fact that clinical trials have strict entry criteria that exclude patients with cardiovascular disease, she said.
 

Radiation risks

Radiation therapy is associated with a more than 7% increase in major coronary events per Gy of mean heart dose, Dr. Liu noted, citing a 2013 study (N Engl J Med. 2013;368:987-98).

Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, said that risk factors for radiation-induced heart disease include anterior or left chest irradiation, cumulative doses above 30 Gy, patient age younger than 50 years, doses of more than 2 Gy per fraction, presence and extent of tumor in or near the heart, lack of radiation shielding, concomitant chemotherapy (especially with anthracyclines), and preexisting cardiovascular disease or risk factors.

Neil Osterweil/MDedge News

Treatment options for LVEF decline

The package insert for trastuzumab recommends withholding the drug for a minimum of 4 weeks if the patient has a 16% or greater decline in LVEF from baseline, or a 10% or greater decline from baseline to below the lower limit of normal. The insert recommends LVEF monitoring every 3 or 4 weeks, and says that trastuzumab can be resumed if LVEF improves to above the lower limit of normal with an absolute decrease from baseline of not more than 15%. The insert also states, however, that “the safety of continuation or resumption of trastuzumab in patients with trastuzumab induced LV dysfunction has never been studied, “ Dr. Liu noted.

She cited an American Society of Clinical Oncology guideline on the prevention and monitoring of cardiac dysfunction in survivors of adult cancers, which states in part that the decision to continue or discontinue cancer therapy in patients with evidence of cardiac dysfunction “made by the oncologist, should be informed by close collaboration with a cardiologist, fully evaluating the clinical circumstances and considering the risks and benefits of continuation of therapy responsible for the cardiac dysfunction.”

“I want to emphasize the importance of accepting and managing cardiovascular risk in patients priors to and during potentially cardiotoxic therapy. To optimize cardiologic and oncologic outcomes, we need to avoid or minimize treatment interruptions of life-saving therapy, and mitigate cardiac events with aggressive cardiovascular risk-factor modification,” Dr. Liu said.

She called for development of better risk stratification tools to tailor cardiac surveillance during therapy, based on both patient-specific and treatment-specific risk factors.

Dr. Liu reported nothing to disclose. Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics. Cota, Dendreon, Ferring Pharmaceuticals. GenomeDx, Janssen, and Nanobiotix.

WASHINGTON – Oncologists and cardiologists need to work hand-in-hand when managing the care of women with breast cancer whose treatment plan includes cardiotoxic therapies and breast irradiation, reported specialists.

Neil Osterweil/MDedge News

Depending on the cancer subtype, women with breast cancer may receive chemotherapy with a cardiotoxic anthracycline such as doxorubicin or epirubicin, or a HER2-targeted agent such as trastuzumab (Herceptin), pertuzumab (Perjeta), or ado-trastuzumab emtansine (Kadcyla).

“The cardiotoxicity related to breast cancer has been a well publicized issue, and chances are your patients know about it and are concerned as well,” Jennifer E. Liu, MD, director of cardiovascular laboratories at Memorial Sloan Kettering Cancer Center in New York, said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Anthracyclines, trastuzumab, and HF

In large adjuvant therapy trials of anthracyclines and trastuzumab in women with breast cancer, doxorubicin alone was associated with an asymptomatic decline in left ventricular ejection fraction (LVEF) of 4% to 11%, and a less than 1% incidence of heart failure (HF), Dr. Liu noted.

When patients received an anthracycline followed by trastuzumab, the incidence of asymptomatic LVEF decline ranged from 4% to 19%, the incidence of clinical HF was 2% to 4%, and the rate of trastuzumab interruption for cardiac adverse events ranged from 5% to 18%.

In comparison, in trials with trastuzumab in combination therapy that did not contain an anthracycline, the risk of cardiovascular complications was lower, with asymptomatic decline in LVEF ranging from 3.2% to 9.4%, and class III/IV HF occurring in just 0.5% of patients. In trials combining trastuzumab and pertuzumab, there were no increases in cardiac toxicity over trastuzumab alone.

Although with longer follow-up, the approximately 4% rate of HF in patients treated with anthracycline-based chemotherapy, paclitaxel, and trastuzumab in the NSABP B-31 trial has not changed significantly; retrospective claims-based studies reflecting daily practice have shown significantly higher rates of HF and or cardiomyopathy, Dr. Liu said.

She cited a 2012 study showing that among 45,537 women with a mean age of 76 years who were treated for breast cancer, the 3-year incidence rates of HF and/or cardiomyopathy were 32% for patients treated with trastuzumab alone, and 41.9% for those treated with an anthracycline followed by trastuzumab. Other, smaller studies also showed lower but significantly elevated risks for the drugs.

The discrepancy between clinical trial and “real world” results may be chalked up to the fact that claims-based data rely on diagnostic codes that may not accurately reflect the actual cardiac diagnosis, and by the fact that clinical trials have strict entry criteria that exclude patients with cardiovascular disease, she said.
 

Radiation risks

Radiation therapy is associated with a more than 7% increase in major coronary events per Gy of mean heart dose, Dr. Liu noted, citing a 2013 study (N Engl J Med. 2013;368:987-98).

Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, said that risk factors for radiation-induced heart disease include anterior or left chest irradiation, cumulative doses above 30 Gy, patient age younger than 50 years, doses of more than 2 Gy per fraction, presence and extent of tumor in or near the heart, lack of radiation shielding, concomitant chemotherapy (especially with anthracyclines), and preexisting cardiovascular disease or risk factors.

Neil Osterweil/MDedge News

Treatment options for LVEF decline

The package insert for trastuzumab recommends withholding the drug for a minimum of 4 weeks if the patient has a 16% or greater decline in LVEF from baseline, or a 10% or greater decline from baseline to below the lower limit of normal. The insert recommends LVEF monitoring every 3 or 4 weeks, and says that trastuzumab can be resumed if LVEF improves to above the lower limit of normal with an absolute decrease from baseline of not more than 15%. The insert also states, however, that “the safety of continuation or resumption of trastuzumab in patients with trastuzumab induced LV dysfunction has never been studied, “ Dr. Liu noted.

She cited an American Society of Clinical Oncology guideline on the prevention and monitoring of cardiac dysfunction in survivors of adult cancers, which states in part that the decision to continue or discontinue cancer therapy in patients with evidence of cardiac dysfunction “made by the oncologist, should be informed by close collaboration with a cardiologist, fully evaluating the clinical circumstances and considering the risks and benefits of continuation of therapy responsible for the cardiac dysfunction.”

“I want to emphasize the importance of accepting and managing cardiovascular risk in patients priors to and during potentially cardiotoxic therapy. To optimize cardiologic and oncologic outcomes, we need to avoid or minimize treatment interruptions of life-saving therapy, and mitigate cardiac events with aggressive cardiovascular risk-factor modification,” Dr. Liu said.

She called for development of better risk stratification tools to tailor cardiac surveillance during therapy, based on both patient-specific and treatment-specific risk factors.

Dr. Liu reported nothing to disclose. Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics. Cota, Dendreon, Ferring Pharmaceuticals. GenomeDx, Janssen, and Nanobiotix.

WASHINGTON – Oncologists and cardiologists need to work hand-in-hand when managing the care of women with breast cancer whose treatment plan includes cardiotoxic therapies and breast irradiation, reported specialists.

Neil Osterweil/MDedge News

Depending on the cancer subtype, women with breast cancer may receive chemotherapy with a cardiotoxic anthracycline such as doxorubicin or epirubicin, or a HER2-targeted agent such as trastuzumab (Herceptin), pertuzumab (Perjeta), or ado-trastuzumab emtansine (Kadcyla).

“The cardiotoxicity related to breast cancer has been a well publicized issue, and chances are your patients know about it and are concerned as well,” Jennifer E. Liu, MD, director of cardiovascular laboratories at Memorial Sloan Kettering Cancer Center in New York, said at the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient meeting.
 

Anthracyclines, trastuzumab, and HF

In large adjuvant therapy trials of anthracyclines and trastuzumab in women with breast cancer, doxorubicin alone was associated with an asymptomatic decline in left ventricular ejection fraction (LVEF) of 4% to 11%, and a less than 1% incidence of heart failure (HF), Dr. Liu noted.

When patients received an anthracycline followed by trastuzumab, the incidence of asymptomatic LVEF decline ranged from 4% to 19%, the incidence of clinical HF was 2% to 4%, and the rate of trastuzumab interruption for cardiac adverse events ranged from 5% to 18%.

In comparison, in trials with trastuzumab in combination therapy that did not contain an anthracycline, the risk of cardiovascular complications was lower, with asymptomatic decline in LVEF ranging from 3.2% to 9.4%, and class III/IV HF occurring in just 0.5% of patients. In trials combining trastuzumab and pertuzumab, there were no increases in cardiac toxicity over trastuzumab alone.

Although with longer follow-up, the approximately 4% rate of HF in patients treated with anthracycline-based chemotherapy, paclitaxel, and trastuzumab in the NSABP B-31 trial has not changed significantly; retrospective claims-based studies reflecting daily practice have shown significantly higher rates of HF and or cardiomyopathy, Dr. Liu said.

She cited a 2012 study showing that among 45,537 women with a mean age of 76 years who were treated for breast cancer, the 3-year incidence rates of HF and/or cardiomyopathy were 32% for patients treated with trastuzumab alone, and 41.9% for those treated with an anthracycline followed by trastuzumab. Other, smaller studies also showed lower but significantly elevated risks for the drugs.

The discrepancy between clinical trial and “real world” results may be chalked up to the fact that claims-based data rely on diagnostic codes that may not accurately reflect the actual cardiac diagnosis, and by the fact that clinical trials have strict entry criteria that exclude patients with cardiovascular disease, she said.
 

Radiation risks

Radiation therapy is associated with a more than 7% increase in major coronary events per Gy of mean heart dose, Dr. Liu noted, citing a 2013 study (N Engl J Med. 2013;368:987-98).

Paul Nguyen, MD, a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, said that risk factors for radiation-induced heart disease include anterior or left chest irradiation, cumulative doses above 30 Gy, patient age younger than 50 years, doses of more than 2 Gy per fraction, presence and extent of tumor in or near the heart, lack of radiation shielding, concomitant chemotherapy (especially with anthracyclines), and preexisting cardiovascular disease or risk factors.

Neil Osterweil/MDedge News

Treatment options for LVEF decline

The package insert for trastuzumab recommends withholding the drug for a minimum of 4 weeks if the patient has a 16% or greater decline in LVEF from baseline, or a 10% or greater decline from baseline to below the lower limit of normal. The insert recommends LVEF monitoring every 3 or 4 weeks, and says that trastuzumab can be resumed if LVEF improves to above the lower limit of normal with an absolute decrease from baseline of not more than 15%. The insert also states, however, that “the safety of continuation or resumption of trastuzumab in patients with trastuzumab induced LV dysfunction has never been studied, “ Dr. Liu noted.

She cited an American Society of Clinical Oncology guideline on the prevention and monitoring of cardiac dysfunction in survivors of adult cancers, which states in part that the decision to continue or discontinue cancer therapy in patients with evidence of cardiac dysfunction “made by the oncologist, should be informed by close collaboration with a cardiologist, fully evaluating the clinical circumstances and considering the risks and benefits of continuation of therapy responsible for the cardiac dysfunction.”

“I want to emphasize the importance of accepting and managing cardiovascular risk in patients priors to and during potentially cardiotoxic therapy. To optimize cardiologic and oncologic outcomes, we need to avoid or minimize treatment interruptions of life-saving therapy, and mitigate cardiac events with aggressive cardiovascular risk-factor modification,” Dr. Liu said.

She called for development of better risk stratification tools to tailor cardiac surveillance during therapy, based on both patient-specific and treatment-specific risk factors.

Dr. Liu reported nothing to disclose. Dr. Nguyen reported consulting fees/honoraria from Astellas, Augmenix, Blue Earth Diagnostics. Cota, Dendreon, Ferring Pharmaceuticals. GenomeDx, Janssen, and Nanobiotix.

A new single-surgeon study suggests that the experience gained from performing more than 60 robot-assisted thoracoscopic (RATS) pulmonary lobectomies could allow surgeons to reach “mastery” and shave about 90 minutes off adjusted operating time.

Master Video/Shutterstock

The findings provide “further support to the adaptation of formalized robotic training and credentialing procedures,” wrote the authors of the retrospective, single-center study, which was presented at the 2018 Academic Surgical Congress and published in Surgery.

According to the study authors, advantages of robotic surgery, compared with thoracoscopic surgery, include “3-dimensional visualization, enhanced maneuverability in small spaces, and the ease of the hilar and mediastinal dissection. Disadvantages include the lack of haptic feedback, increased cost, and increased operative time.”

In the new study, the authors, led by thoracic surgeon Brian N. Arnold, MD, of Yale University, New Haven, Conn., attempted to quantify the learning curve in RATS pulmonary lobectomies by using a more “statistically rigorous” technique than previous studies.

The study tracked 101 of 116 consecutive patients who underwent RATS pulmonary lobectomy at a single unnamed center from 2010 to 2016. Some patients, such as those who underwent a right middle lobectomy that is considered an easier procedure, were excluded. All patients were treated by the same unidentified surgeon.

Researchers identified three phases of the RATS learning curve: cases 1-22, cases 23-63, and cases 64-101.

On average, the patients were aged 69 years; 52% were female. Overall, a third of the patients developed complications.

After controlling for various factors, the researchers found that adjusted operating time and estimated blood loss were statistically different between the first and second phases (P less than .05 and P = .016, respectively). They were also different between the first and third phases (P less than .05 and P = .006, respectively).

Specifically, operating time in the first phase was a mean of 256 minutes versus 195 minutes in the second phase (P = .0002) and 168 minutes in the third phase (P less than .0001). Blood loss was 200 mL (interquartile range, 150-300 mL) in the first phase versus 150 mL (IQR, 75-200 mL; P = .0219) in the second phase and 150 mL (IQR, 100-150 mL; P = .0096) in the third phase.

The researchers found no statistically significant evidence that the surgeon’s growing experience affected length of stay, postoperative complications, chest tube duration, or conversion rate. No patients died within 30 or 90 days.

The researchers also compared operating time, length of stay, and complication rate in the RATS procedures with those in video-assisted thoracoscopic (VATS) lobectomies performed at the same institution from 2008 to 2014. There was only a statistically significant difference in mean operating time (RATS, 319 minutes; VATS, 253 minutes; P less than .001)

The study authors noted that the surgeon had extensive previous experience with VATS procedures. “Therefore, for better or for worse, the results may not apply to surgeons without this experience who move from open surgery to robotic surgery.”

Study funding and disclosures were not reported.

SOURCE: Arnold BN et al. Surgery. 2019 Feb;165(2):450-4.

A new single-surgeon study suggests that the experience gained from performing more than 60 robot-assisted thoracoscopic (RATS) pulmonary lobectomies could allow surgeons to reach “mastery” and shave about 90 minutes off adjusted operating time.

Master Video/Shutterstock

The findings provide “further support to the adaptation of formalized robotic training and credentialing procedures,” wrote the authors of the retrospective, single-center study, which was presented at the 2018 Academic Surgical Congress and published in Surgery.

According to the study authors, advantages of robotic surgery, compared with thoracoscopic surgery, include “3-dimensional visualization, enhanced maneuverability in small spaces, and the ease of the hilar and mediastinal dissection. Disadvantages include the lack of haptic feedback, increased cost, and increased operative time.”

In the new study, the authors, led by thoracic surgeon Brian N. Arnold, MD, of Yale University, New Haven, Conn., attempted to quantify the learning curve in RATS pulmonary lobectomies by using a more “statistically rigorous” technique than previous studies.

The study tracked 101 of 116 consecutive patients who underwent RATS pulmonary lobectomy at a single unnamed center from 2010 to 2016. Some patients, such as those who underwent a right middle lobectomy that is considered an easier procedure, were excluded. All patients were treated by the same unidentified surgeon.

Researchers identified three phases of the RATS learning curve: cases 1-22, cases 23-63, and cases 64-101.

On average, the patients were aged 69 years; 52% were female. Overall, a third of the patients developed complications.

After controlling for various factors, the researchers found that adjusted operating time and estimated blood loss were statistically different between the first and second phases (P less than .05 and P = .016, respectively). They were also different between the first and third phases (P less than .05 and P = .006, respectively).

Specifically, operating time in the first phase was a mean of 256 minutes versus 195 minutes in the second phase (P = .0002) and 168 minutes in the third phase (P less than .0001). Blood loss was 200 mL (interquartile range, 150-300 mL) in the first phase versus 150 mL (IQR, 75-200 mL; P = .0219) in the second phase and 150 mL (IQR, 100-150 mL; P = .0096) in the third phase.

The researchers found no statistically significant evidence that the surgeon’s growing experience affected length of stay, postoperative complications, chest tube duration, or conversion rate. No patients died within 30 or 90 days.

The researchers also compared operating time, length of stay, and complication rate in the RATS procedures with those in video-assisted thoracoscopic (VATS) lobectomies performed at the same institution from 2008 to 2014. There was only a statistically significant difference in mean operating time (RATS, 319 minutes; VATS, 253 minutes; P less than .001)

The study authors noted that the surgeon had extensive previous experience with VATS procedures. “Therefore, for better or for worse, the results may not apply to surgeons without this experience who move from open surgery to robotic surgery.”

Study funding and disclosures were not reported.

SOURCE: Arnold BN et al. Surgery. 2019 Feb;165(2):450-4.

A new single-surgeon study suggests that the experience gained from performing more than 60 robot-assisted thoracoscopic (RATS) pulmonary lobectomies could allow surgeons to reach “mastery” and shave about 90 minutes off adjusted operating time.

Master Video/Shutterstock

The findings provide “further support to the adaptation of formalized robotic training and credentialing procedures,” wrote the authors of the retrospective, single-center study, which was presented at the 2018 Academic Surgical Congress and published in Surgery.

According to the study authors, advantages of robotic surgery, compared with thoracoscopic surgery, include “3-dimensional visualization, enhanced maneuverability in small spaces, and the ease of the hilar and mediastinal dissection. Disadvantages include the lack of haptic feedback, increased cost, and increased operative time.”

In the new study, the authors, led by thoracic surgeon Brian N. Arnold, MD, of Yale University, New Haven, Conn., attempted to quantify the learning curve in RATS pulmonary lobectomies by using a more “statistically rigorous” technique than previous studies.

The study tracked 101 of 116 consecutive patients who underwent RATS pulmonary lobectomy at a single unnamed center from 2010 to 2016. Some patients, such as those who underwent a right middle lobectomy that is considered an easier procedure, were excluded. All patients were treated by the same unidentified surgeon.

Researchers identified three phases of the RATS learning curve: cases 1-22, cases 23-63, and cases 64-101.

On average, the patients were aged 69 years; 52% were female. Overall, a third of the patients developed complications.

After controlling for various factors, the researchers found that adjusted operating time and estimated blood loss were statistically different between the first and second phases (P less than .05 and P = .016, respectively). They were also different between the first and third phases (P less than .05 and P = .006, respectively).

Specifically, operating time in the first phase was a mean of 256 minutes versus 195 minutes in the second phase (P = .0002) and 168 minutes in the third phase (P less than .0001). Blood loss was 200 mL (interquartile range, 150-300 mL) in the first phase versus 150 mL (IQR, 75-200 mL; P = .0219) in the second phase and 150 mL (IQR, 100-150 mL; P = .0096) in the third phase.

The researchers found no statistically significant evidence that the surgeon’s growing experience affected length of stay, postoperative complications, chest tube duration, or conversion rate. No patients died within 30 or 90 days.

The researchers also compared operating time, length of stay, and complication rate in the RATS procedures with those in video-assisted thoracoscopic (VATS) lobectomies performed at the same institution from 2008 to 2014. There was only a statistically significant difference in mean operating time (RATS, 319 minutes; VATS, 253 minutes; P less than .001)

The study authors noted that the surgeon had extensive previous experience with VATS procedures. “Therefore, for better or for worse, the results may not apply to surgeons without this experience who move from open surgery to robotic surgery.”

Study funding and disclosures were not reported.

SOURCE: Arnold BN et al. Surgery. 2019 Feb;165(2):450-4.

The Food and Drug Administration issued a letter on Feb. 4, 2019, to health care providers regarding interim results from a postapproval study for Abiomed’s Impella RP System because these results appear to have a higher mortality rate than was seen in premarket clinical studies.

The Impella RP system was approved in 2017 to help patients maintain stable heart function for up to 14 days without open chest surgery. As a condition of its approval, the FDA mandated Abiomed to perform a postapproval study (PAS); this study reflects use in a broader population than the premarket studies, which adhered to stricter inclusion and exclusion criteria.

Earlier in January, Abiomed submitted data to the FDA suggesting that differences in preimplant characteristics between patients in the PAS and those in the premarket clinical studies may explain the difference in mortality. Specifically, 16 of the 23 patients enrolled in the PAS would not have met the enrollment criteria for the premarket clinical studies because they were in cardiogenic shock for longer than 48 hours, experienced an in-hospital cardiac arrest, were treated with an intra-aortic balloon pump, or suffered a preimplant hypoxic or ischemic neurologic event.

“Although the FDA is concerned about the high mortality rate from the interim PAS results,” they wrote in the letter, which is available on the FDA website, “we believe that, when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP system continue to outweigh the risks.”

cpalmer@mdedge.com

The Food and Drug Administration issued a letter on Feb. 4, 2019, to health care providers regarding interim results from a postapproval study for Abiomed’s Impella RP System because these results appear to have a higher mortality rate than was seen in premarket clinical studies.

The Impella RP system was approved in 2017 to help patients maintain stable heart function for up to 14 days without open chest surgery. As a condition of its approval, the FDA mandated Abiomed to perform a postapproval study (PAS); this study reflects use in a broader population than the premarket studies, which adhered to stricter inclusion and exclusion criteria.

Earlier in January, Abiomed submitted data to the FDA suggesting that differences in preimplant characteristics between patients in the PAS and those in the premarket clinical studies may explain the difference in mortality. Specifically, 16 of the 23 patients enrolled in the PAS would not have met the enrollment criteria for the premarket clinical studies because they were in cardiogenic shock for longer than 48 hours, experienced an in-hospital cardiac arrest, were treated with an intra-aortic balloon pump, or suffered a preimplant hypoxic or ischemic neurologic event.

“Although the FDA is concerned about the high mortality rate from the interim PAS results,” they wrote in the letter, which is available on the FDA website, “we believe that, when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP system continue to outweigh the risks.”

cpalmer@mdedge.com

The Food and Drug Administration issued a letter on Feb. 4, 2019, to health care providers regarding interim results from a postapproval study for Abiomed’s Impella RP System because these results appear to have a higher mortality rate than was seen in premarket clinical studies.

The Impella RP system was approved in 2017 to help patients maintain stable heart function for up to 14 days without open chest surgery. As a condition of its approval, the FDA mandated Abiomed to perform a postapproval study (PAS); this study reflects use in a broader population than the premarket studies, which adhered to stricter inclusion and exclusion criteria.

Earlier in January, Abiomed submitted data to the FDA suggesting that differences in preimplant characteristics between patients in the PAS and those in the premarket clinical studies may explain the difference in mortality. Specifically, 16 of the 23 patients enrolled in the PAS would not have met the enrollment criteria for the premarket clinical studies because they were in cardiogenic shock for longer than 48 hours, experienced an in-hospital cardiac arrest, were treated with an intra-aortic balloon pump, or suffered a preimplant hypoxic or ischemic neurologic event.

“Although the FDA is concerned about the high mortality rate from the interim PAS results,” they wrote in the letter, which is available on the FDA website, “we believe that, when the device is used for the currently approved indication in appropriately selected patients, the benefits of the Impella RP system continue to outweigh the risks.”

cpalmer@mdedge.com

Family histories of psoriasis and of psoriatic arthritis have different effects on skin phenotypes, disease severity, and musculoskeletal features, the results of a retrospective cohort study suggest.

A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.

“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.

Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.


The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.

Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.

Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.

In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.

Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.

Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).

Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.

SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.

Family histories of psoriasis and of psoriatic arthritis have different effects on skin phenotypes, disease severity, and musculoskeletal features, the results of a retrospective cohort study suggest.

A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.

“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.

Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.


The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.

Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.

Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.

In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.

Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.

Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).

Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.

SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.

Family histories of psoriasis and of psoriatic arthritis have different effects on skin phenotypes, disease severity, and musculoskeletal features, the results of a retrospective cohort study suggest.

A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.

“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.

Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.


The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.

Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.

Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.

In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.

Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.

Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).

Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.

SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.

In this episode, Gary H. Lyman, MD (https://bitly.is/2UJzUly) joins David Henry, MD, (http://bit.ly/2MFDfzm) to talk about biosimilars. 

Dr. Lyman talks about the definition of biosimilars, how they are made, which are approved, and which ones are on the market. 

He also talks about extrapolation and interchangeability as well as where some biosimilars stand in both ASCO and NCCN guidelines for patients who are going into supportive care. 

And Ilana Yurkiewicz, MD (https://stanford.io/2RXPixR), talks about what the word "cure" means to you compared to what it means to patients in a world with OS, PFS, DFS, CR, etc. (26:35). 

Subscribe here:

Apple Podcasts
Google Podcasts

Show Notes

By Hitomi Hosoya, MD, PhD

- Biosimilars are biologic products that are highly similar to the reference products with no clinically meaningful difference in terms of safety, efficacy, purity, and potency.

- Unlike “generic” products, biosimilars are produced in living systems, therefore they cannot be replicated identically. 

- The Food and Drug Administration encourages companies to produce biosimilars as a patent expires on the original product.

- For approval, the FDA requires largely preclinical data; amino acid sequence and molecular structures, pharmacodynamics and pharmacokinetic data in animal models and humans. Also, no greater immunogenicity should be demonstrated.

- Large randomized trials are not usually required for approval of biosimilars as there is already data on the original product. Post-marketing surveillance is important.

- 14 biosimilars have already been approved by the FDA.

- Interchangeable designation of biosimilars is yet to come.

- At this early stage of biosimilar marketing, we see a 10%-11% cost reduction. This is expected to increase as the market expands.

References:

 JAMA Oncol.2018 Feb 1;4(2):241-247

 JCSO 2018;16(6):e283-e289.

Contact us: podcasts@mdedge.com

MDedge Hematology/Oncology Twitter: @MDedgeHemOnc

Ilana Yurkiewicz Twitter: @ilanayurkiewicz

In this episode, Gary H. Lyman, MD (https://bitly.is/2UJzUly) joins David Henry, MD, (http://bit.ly/2MFDfzm) to talk about biosimilars. 

Dr. Lyman talks about the definition of biosimilars, how they are made, which are approved, and which ones are on the market. 

He also talks about extrapolation and interchangeability as well as where some biosimilars stand in both ASCO and NCCN guidelines for patients who are going into supportive care. 

And Ilana Yurkiewicz, MD (https://stanford.io/2RXPixR), talks about what the word "cure" means to you compared to what it means to patients in a world with OS, PFS, DFS, CR, etc. (26:35). 

Subscribe here:

Apple Podcasts
Google Podcasts

Show Notes

By Hitomi Hosoya, MD, PhD

- Biosimilars are biologic products that are highly similar to the reference products with no clinically meaningful difference in terms of safety, efficacy, purity, and potency.

- Unlike “generic” products, biosimilars are produced in living systems, therefore they cannot be replicated identically. 

- The Food and Drug Administration encourages companies to produce biosimilars as a patent expires on the original product.

- For approval, the FDA requires largely preclinical data; amino acid sequence and molecular structures, pharmacodynamics and pharmacokinetic data in animal models and humans. Also, no greater immunogenicity should be demonstrated.

- Large randomized trials are not usually required for approval of biosimilars as there is already data on the original product. Post-marketing surveillance is important.

- 14 biosimilars have already been approved by the FDA.

- Interchangeable designation of biosimilars is yet to come.

- At this early stage of biosimilar marketing, we see a 10%-11% cost reduction. This is expected to increase as the market expands.

References:

 JAMA Oncol.2018 Feb 1;4(2):241-247

 JCSO 2018;16(6):e283-e289.

Contact us: podcasts@mdedge.com

MDedge Hematology/Oncology Twitter: @MDedgeHemOnc

Ilana Yurkiewicz Twitter: @ilanayurkiewicz

In this episode, Gary H. Lyman, MD (https://bitly.is/2UJzUly) joins David Henry, MD, (http://bit.ly/2MFDfzm) to talk about biosimilars. 

Dr. Lyman talks about the definition of biosimilars, how they are made, which are approved, and which ones are on the market. 

He also talks about extrapolation and interchangeability as well as where some biosimilars stand in both ASCO and NCCN guidelines for patients who are going into supportive care. 

And Ilana Yurkiewicz, MD (https://stanford.io/2RXPixR), talks about what the word "cure" means to you compared to what it means to patients in a world with OS, PFS, DFS, CR, etc. (26:35). 

Subscribe here:

Apple Podcasts
Google Podcasts

Show Notes

By Hitomi Hosoya, MD, PhD

- Biosimilars are biologic products that are highly similar to the reference products with no clinically meaningful difference in terms of safety, efficacy, purity, and potency.

- Unlike “generic” products, biosimilars are produced in living systems, therefore they cannot be replicated identically. 

- The Food and Drug Administration encourages companies to produce biosimilars as a patent expires on the original product.

- For approval, the FDA requires largely preclinical data; amino acid sequence and molecular structures, pharmacodynamics and pharmacokinetic data in animal models and humans. Also, no greater immunogenicity should be demonstrated.

- Large randomized trials are not usually required for approval of biosimilars as there is already data on the original product. Post-marketing surveillance is important.

- 14 biosimilars have already been approved by the FDA.

- Interchangeable designation of biosimilars is yet to come.

- At this early stage of biosimilar marketing, we see a 10%-11% cost reduction. This is expected to increase as the market expands.

References:

 JAMA Oncol.2018 Feb 1;4(2):241-247

 JCSO 2018;16(6):e283-e289.

Contact us: podcasts@mdedge.com

MDedge Hematology/Oncology Twitter: @MDedgeHemOnc

Ilana Yurkiewicz Twitter: @ilanayurkiewicz