It has been estimated that 2 million serious adverse drug reactions (ADRs) occur annually in the United States, resulting in 100,000 deaths.¹ Although the acute morbidity and mortality of these ADRs are readily apparent, postdischarge sequalae are critical aspects of a patient’s care. Herein, we present an approach to outpatient dermatologic follow-up of 3 ADRs: acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). For these ADRs, the first step is prompt diagnosis and discontinuation of any potentially causative medications.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

Ninety percent of the time, AGEP is caused by medications, most commonly antibiotics, and less often it is caused by viruses.^2-4 It presents as a cutaneous eruption with nonfollicular sterile pustules, fever, and leukocytosis, usually within 5 days after starting a causative medication.⁵ After stopping the medication, cutaneous findings generally improve within 1 week, and leukocytosis often resolves within 1 week.³

Notable Sequelae

Although AGEP typically is considered benign,² there have been reports of severe sequelae including death from a systemic inflammatory response and complications such as bacterial superinfection and sepsis.^6,7 Visceral involvement can be seen in up to 20% of AGEP patients, with systemic symptoms similar  to those seen in DRESS syndrome. Mortality has been reported in up to 5% of cases, mainly in patients with comorbidities and notable mucosal involvement.⁸ More severe disease can be seen in patients with known dermatologic disease, as AGEP can provoke an isomorphic phenomenon.⁹ Laboratory alterations typically seen in AGEP include neutrophilia, eosinophilia, and elevated liver enzymes.²

Follow-up Recommendations

Patients should be informed of the expected timeline for resolution and should be counseled on the possibility of rare systemic symptoms. Laboratory abnormalities should be monitored every 2 to 4 weeks until normalized.

DRESS SYNDROME

DRESS syndrome is characterized by a morbilliform eruption that can be accompanied by fever; eosinophilia; purpura; facial edema; lymphadenopathy; and liver, renal, or other organ dysfunction. DRESS syndrome most often presents within 8 weeks of exposure to a causative drug.^10,11 The most common causative agents are anticonvulsants, antimicrobials, and allopurinol.¹² Treatment includes topical corticosteroids and systemic corticosteroids for internal organ involvement.¹⁰

Short-term Sequelae

Several potential sequelae may occur within 6 months of resolution of DRESS syndrome, resulting from both the ADR itself and/or systemic corticosteroids that often are required for treatment.¹³ Complications secondary to herpesviruses have been reported.¹⁴ Cases of cytomegalovirus-induced gastric ulcers can lead to gastrointestinal tract bleeds.¹⁵

Infections including Cryptococcus species and herpes zoster also have been reported.¹⁶ Patients, particularly those treated with systemic corticosteroids, should be monitored with close follow-up for infectious complications and treatment-related adverse effects.¹³

Long-term Sequelae

Endocrine
Thyroid gland abnormalities secondary to DRESS syndrome include Graves disease and Hashimoto disease as well as variations in biomarkers including elevated free thyroxine and low and elevated thyroid-stimulating hormone levels.^16,17 Type 1 diabetes mellitus also has been seen after DRESS syndrome, developing within the first 10 months after onset with unknown pathogenesis.¹⁸

Autoimmune
Other reported sequelae of DRESS syndrome include elevated antinuclear antibodies with possible development into systemic lupus erythematosus, autoimmune hemolytic anemia, vitiligo, and rheumatoid arthritis.^11,16 Symptoms may be exacerbated in patients with preexisting autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and patients with preexisting renal disease are at an increased risk for requiring lifelong hemodialysis after DRESS syndrome.¹⁶

Other
Studies have demonstrated that pneumonia, thrombosis, and alopecia can be complications of DRESS syndrome.^11,16 Psychiatric disturbances including fear of taking new medications, anxiety, and depression also have been reported.¹⁹ Children with DRESS syndrome may develop vitiligo, alopecia, sclerodermatous lesions, photophobia, uveitis, and Vogt-Koyanagi-Harada disease.¹⁷

Follow-up Recommendations

It is important to inform patients of both the potential short-term and long-term sequelae of DRESS syndrome, including those associated with treatment. A thorough review of systems should be performed at each visit, along with laboratory evaluation including a complete blood cell count with differential and liver function testing every 1 to 2 weeks after discharge until normalized, with monthly monitoring of glucose, thyroid-stimulating hormone, and free thyroxine levels for 3 months after discharge.

STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS

Stevens-Johnson syndrome/toxic epidermal necrolysis are severe ADRs that present with dusky violaceous macules. Inciting medications include nonsteroidal anti-inflammatory drugs, allopurinol, antibiotics, and anticonvulsants, and symptoms begin 1 to 3 weeks after medication exposure.¹² Initially, the lesions often begin on the trunk and can progress to full-body erythema and exfoliation with a necrotic epidermis and mucosal involvement.^12,20

Notable Sequelae

Cutaneous
Chronic eczema can present at any time and can vary in severity in SJS/TEN patients.²¹ Xerosis and pruritus can be treated with emollients.¹¹ Dyschromia is common. Hypertrophic and keloidal scarring can result from surgical debridement and are best prevented with the use of nonadherent dressings.²² Nail changes such as anonychia, dystrophy, longitudinal ridges, and pterygium also are seen, and topical steroids can be helpful. Other reported dermatologic sequelae include dyschromia and eruption of ectopic sebaceous glands.^21,22

Ocular
Ocular sequelae include dry eyes, photophobia, symblepharon, corneal scarring, corneal neovascularization, corneal xerosis, trichiasis, reduced visual acuity, blindness, and subconjunctival fibrosis. The most common sequelae are bilateral conjunctivitis and corneal ulcerations.^22,23 Early and regular ophthalmologic follow-up is recommended, as SJS/TEN-induced blindness can result from delayed therapy, destroying corneal stem cells.²¹ Amniotic membrane transplantation replaces the damaged corneal membrane, which may reduce corneal inflammation.²⁴

Chronic dry eye syndrome can recur for years after SJS/TEN resolves and progresses over time.²² Frequent use of nonpreserved artificial tears and salivary gland transplantation can be helpful.²⁴ Unfortunately, ocular disease may develop months after discharge; therefore, it is recommended that dermatologists ask all SJS/TEN patients about ocular symptoms in follow-up visits. If ocular involvement was present initially, patients should be followed by ophthalmology for at least 1 year after discharge.²³

Genitourinary
Genitourinary sequelae in SJS/TEN include adhesions, particularly in the female urethra and vaginal opening; vaginal adenosis; vulvovaginal endometriosis; and persistent genital ulcerations most commonly reported in females.²² Prompt inpatient gynecologic or urologic consultation is critical to reduce these potentially permanent outcomes. Topical corticosteroid therapy is recommended in the acute phase.²²

Psychologic
Posttraumatic stress disorder may occur in patients with SJS/TEN. One study showed that 23% (7/30) of patients had posttraumatic stress disorder 6 months after hospitalization for SJS/TEN. The investigators recommended routine psychiatric assessment in the acute disease period and for at least 1 year after discharge.²⁵

Pulmonary, Gastrointestinal, and Renal
Interstitial pneumonia and obliterative bronchitis/bronchiolitis can be caused by SJS/TEN. Interstitial pneumonia tends to occur during the acute course, while obliterative airway disease manifests after resolution of SJS/TEN.^21,22 Abnormal pulmonary function testing can be seen in more than half of SJS/TEN patients 2 months after the ADR.²² Gastrointestinal sequelae include esophageal strictures, intestinal ulceration, and cholestasis.²² Renal sequelae include acute kidney injury and glomerulonephritis, which may be secondary to the volume loss seen in SJS/TEN but may be irreversible.²¹

Special Populations
A correlation with infertility in women has been documented in patients with SJS/TEN; thus, follow-up with obstetrics and gynecology is recommended in women of child-bearing potential. The most considerable risk in pregnant women with SJS/TEN is premature birth, and mucosal necrosis of SJS/TEN can impair vaginal delivery.²⁶ Antiretrovirals can be a cause of SJS/TEN in the human immunodeficiency virus–positive population.²⁷ In those cases, it is best to discontinue the medication and find an alternative.

Risk factors for children can be different and can include viral and febrile illnesses as well as mycoplasma infection.²⁸ Children also can be at an increased risk for poor ocular outcomes, such as permanent deficiency in visual acuity and blindness.²⁹

Follow-up Recommendations

Patients should be counseled regarding sequelae and the multisystem nature of SJS/TEN. Inpatient referrals should be given as needed. It is important to watch for ocular symptoms for 1 year after SJS/TEN resolution. When ocular involvement is present, follow-up with ophthalmology is recommended within 1 month of discharge and then at the discretion of the ophthalmologist. Pulmonary function should be monitored for 1 year after SJS/TEN, starting 1 month after discharge and then at the discretion of the pulmonologist. Patients also should be screened for psychologic sequelae for at least 1 year after discharge.

FINAL THOUGHTS

Adverse drug reactions are notable causes of inpatient hospitalization and may lead to considerable sequelae. These ADRs range in severity from more common and benign maculopapular exanthems to severe multiorgan ADRs such as DRESS syndrome and SJS/TEN.

In AGEP, it is important to monitor patients with preexisting dermatologic diseases and to screen for visceral involvement. DRESS syndrome has the potential to cause immune dysregulation and variable long-term adverse sequelae, both from the disease itself and from corticosteroid therapy. Mucocutaneous sequelae of SJS/TEN can potentially affect a patient’s cutaneous, ocular, genitourinary, mental, pulmonary, gastrointestinal, and renal health.

The baseline recommendations provided here warrant more frequent monitoring if the findings and symptoms are severe. In all of these cases, if a causative medication is identified, it should be added to the patient’s allergy list and the patient should be counseled extensively to avoid this medication and other medications in the same class. If a single agent cannot be identified, referrals for patch testing may be of some utility, particularly in AGEP and DRESS syndrome.^30,31

It has been estimated that 2 million serious adverse drug reactions (ADRs) occur annually in the United States, resulting in 100,000 deaths.¹ Although the acute morbidity and mortality of these ADRs are readily apparent, postdischarge sequalae are critical aspects of a patient’s care. Herein, we present an approach to outpatient dermatologic follow-up of 3 ADRs: acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). For these ADRs, the first step is prompt diagnosis and discontinuation of any potentially causative medications.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

Ninety percent of the time, AGEP is caused by medications, most commonly antibiotics, and less often it is caused by viruses.^2-4 It presents as a cutaneous eruption with nonfollicular sterile pustules, fever, and leukocytosis, usually within 5 days after starting a causative medication.⁵ After stopping the medication, cutaneous findings generally improve within 1 week, and leukocytosis often resolves within 1 week.³

Notable Sequelae

Although AGEP typically is considered benign,² there have been reports of severe sequelae including death from a systemic inflammatory response and complications such as bacterial superinfection and sepsis.^6,7 Visceral involvement can be seen in up to 20% of AGEP patients, with systemic symptoms similar  to those seen in DRESS syndrome. Mortality has been reported in up to 5% of cases, mainly in patients with comorbidities and notable mucosal involvement.⁸ More severe disease can be seen in patients with known dermatologic disease, as AGEP can provoke an isomorphic phenomenon.⁹ Laboratory alterations typically seen in AGEP include neutrophilia, eosinophilia, and elevated liver enzymes.²

Follow-up Recommendations

Patients should be informed of the expected timeline for resolution and should be counseled on the possibility of rare systemic symptoms. Laboratory abnormalities should be monitored every 2 to 4 weeks until normalized.

DRESS SYNDROME

DRESS syndrome is characterized by a morbilliform eruption that can be accompanied by fever; eosinophilia; purpura; facial edema; lymphadenopathy; and liver, renal, or other organ dysfunction. DRESS syndrome most often presents within 8 weeks of exposure to a causative drug.^10,11 The most common causative agents are anticonvulsants, antimicrobials, and allopurinol.¹² Treatment includes topical corticosteroids and systemic corticosteroids for internal organ involvement.¹⁰

Short-term Sequelae

Several potential sequelae may occur within 6 months of resolution of DRESS syndrome, resulting from both the ADR itself and/or systemic corticosteroids that often are required for treatment.¹³ Complications secondary to herpesviruses have been reported.¹⁴ Cases of cytomegalovirus-induced gastric ulcers can lead to gastrointestinal tract bleeds.¹⁵

Infections including Cryptococcus species and herpes zoster also have been reported.¹⁶ Patients, particularly those treated with systemic corticosteroids, should be monitored with close follow-up for infectious complications and treatment-related adverse effects.¹³

Long-term Sequelae

Endocrine
Thyroid gland abnormalities secondary to DRESS syndrome include Graves disease and Hashimoto disease as well as variations in biomarkers including elevated free thyroxine and low and elevated thyroid-stimulating hormone levels.^16,17 Type 1 diabetes mellitus also has been seen after DRESS syndrome, developing within the first 10 months after onset with unknown pathogenesis.¹⁸

Autoimmune
Other reported sequelae of DRESS syndrome include elevated antinuclear antibodies with possible development into systemic lupus erythematosus, autoimmune hemolytic anemia, vitiligo, and rheumatoid arthritis.^11,16 Symptoms may be exacerbated in patients with preexisting autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and patients with preexisting renal disease are at an increased risk for requiring lifelong hemodialysis after DRESS syndrome.¹⁶

Other
Studies have demonstrated that pneumonia, thrombosis, and alopecia can be complications of DRESS syndrome.^11,16 Psychiatric disturbances including fear of taking new medications, anxiety, and depression also have been reported.¹⁹ Children with DRESS syndrome may develop vitiligo, alopecia, sclerodermatous lesions, photophobia, uveitis, and Vogt-Koyanagi-Harada disease.¹⁷

Follow-up Recommendations

It is important to inform patients of both the potential short-term and long-term sequelae of DRESS syndrome, including those associated with treatment. A thorough review of systems should be performed at each visit, along with laboratory evaluation including a complete blood cell count with differential and liver function testing every 1 to 2 weeks after discharge until normalized, with monthly monitoring of glucose, thyroid-stimulating hormone, and free thyroxine levels for 3 months after discharge.

STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS

Stevens-Johnson syndrome/toxic epidermal necrolysis are severe ADRs that present with dusky violaceous macules. Inciting medications include nonsteroidal anti-inflammatory drugs, allopurinol, antibiotics, and anticonvulsants, and symptoms begin 1 to 3 weeks after medication exposure.¹² Initially, the lesions often begin on the trunk and can progress to full-body erythema and exfoliation with a necrotic epidermis and mucosal involvement.^12,20

Notable Sequelae

Cutaneous
Chronic eczema can present at any time and can vary in severity in SJS/TEN patients.²¹ Xerosis and pruritus can be treated with emollients.¹¹ Dyschromia is common. Hypertrophic and keloidal scarring can result from surgical debridement and are best prevented with the use of nonadherent dressings.²² Nail changes such as anonychia, dystrophy, longitudinal ridges, and pterygium also are seen, and topical steroids can be helpful. Other reported dermatologic sequelae include dyschromia and eruption of ectopic sebaceous glands.^21,22

Ocular
Ocular sequelae include dry eyes, photophobia, symblepharon, corneal scarring, corneal neovascularization, corneal xerosis, trichiasis, reduced visual acuity, blindness, and subconjunctival fibrosis. The most common sequelae are bilateral conjunctivitis and corneal ulcerations.^22,23 Early and regular ophthalmologic follow-up is recommended, as SJS/TEN-induced blindness can result from delayed therapy, destroying corneal stem cells.²¹ Amniotic membrane transplantation replaces the damaged corneal membrane, which may reduce corneal inflammation.²⁴

Chronic dry eye syndrome can recur for years after SJS/TEN resolves and progresses over time.²² Frequent use of nonpreserved artificial tears and salivary gland transplantation can be helpful.²⁴ Unfortunately, ocular disease may develop months after discharge; therefore, it is recommended that dermatologists ask all SJS/TEN patients about ocular symptoms in follow-up visits. If ocular involvement was present initially, patients should be followed by ophthalmology for at least 1 year after discharge.²³

Genitourinary
Genitourinary sequelae in SJS/TEN include adhesions, particularly in the female urethra and vaginal opening; vaginal adenosis; vulvovaginal endometriosis; and persistent genital ulcerations most commonly reported in females.²² Prompt inpatient gynecologic or urologic consultation is critical to reduce these potentially permanent outcomes. Topical corticosteroid therapy is recommended in the acute phase.²²

Psychologic
Posttraumatic stress disorder may occur in patients with SJS/TEN. One study showed that 23% (7/30) of patients had posttraumatic stress disorder 6 months after hospitalization for SJS/TEN. The investigators recommended routine psychiatric assessment in the acute disease period and for at least 1 year after discharge.²⁵

Pulmonary, Gastrointestinal, and Renal
Interstitial pneumonia and obliterative bronchitis/bronchiolitis can be caused by SJS/TEN. Interstitial pneumonia tends to occur during the acute course, while obliterative airway disease manifests after resolution of SJS/TEN.^21,22 Abnormal pulmonary function testing can be seen in more than half of SJS/TEN patients 2 months after the ADR.²² Gastrointestinal sequelae include esophageal strictures, intestinal ulceration, and cholestasis.²² Renal sequelae include acute kidney injury and glomerulonephritis, which may be secondary to the volume loss seen in SJS/TEN but may be irreversible.²¹

Special Populations
A correlation with infertility in women has been documented in patients with SJS/TEN; thus, follow-up with obstetrics and gynecology is recommended in women of child-bearing potential. The most considerable risk in pregnant women with SJS/TEN is premature birth, and mucosal necrosis of SJS/TEN can impair vaginal delivery.²⁶ Antiretrovirals can be a cause of SJS/TEN in the human immunodeficiency virus–positive population.²⁷ In those cases, it is best to discontinue the medication and find an alternative.

Risk factors for children can be different and can include viral and febrile illnesses as well as mycoplasma infection.²⁸ Children also can be at an increased risk for poor ocular outcomes, such as permanent deficiency in visual acuity and blindness.²⁹

Follow-up Recommendations

Patients should be counseled regarding sequelae and the multisystem nature of SJS/TEN. Inpatient referrals should be given as needed. It is important to watch for ocular symptoms for 1 year after SJS/TEN resolution. When ocular involvement is present, follow-up with ophthalmology is recommended within 1 month of discharge and then at the discretion of the ophthalmologist. Pulmonary function should be monitored for 1 year after SJS/TEN, starting 1 month after discharge and then at the discretion of the pulmonologist. Patients also should be screened for psychologic sequelae for at least 1 year after discharge.

FINAL THOUGHTS

Adverse drug reactions are notable causes of inpatient hospitalization and may lead to considerable sequelae. These ADRs range in severity from more common and benign maculopapular exanthems to severe multiorgan ADRs such as DRESS syndrome and SJS/TEN.

In AGEP, it is important to monitor patients with preexisting dermatologic diseases and to screen for visceral involvement. DRESS syndrome has the potential to cause immune dysregulation and variable long-term adverse sequelae, both from the disease itself and from corticosteroid therapy. Mucocutaneous sequelae of SJS/TEN can potentially affect a patient’s cutaneous, ocular, genitourinary, mental, pulmonary, gastrointestinal, and renal health.

The baseline recommendations provided here warrant more frequent monitoring if the findings and symptoms are severe. In all of these cases, if a causative medication is identified, it should be added to the patient’s allergy list and the patient should be counseled extensively to avoid this medication and other medications in the same class. If a single agent cannot be identified, referrals for patch testing may be of some utility, particularly in AGEP and DRESS syndrome.^30,31

It has been estimated that 2 million serious adverse drug reactions (ADRs) occur annually in the United States, resulting in 100,000 deaths.¹ Although the acute morbidity and mortality of these ADRs are readily apparent, postdischarge sequalae are critical aspects of a patient’s care. Herein, we present an approach to outpatient dermatologic follow-up of 3 ADRs: acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). For these ADRs, the first step is prompt diagnosis and discontinuation of any potentially causative medications.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

Ninety percent of the time, AGEP is caused by medications, most commonly antibiotics, and less often it is caused by viruses.^2-4 It presents as a cutaneous eruption with nonfollicular sterile pustules, fever, and leukocytosis, usually within 5 days after starting a causative medication.⁵ After stopping the medication, cutaneous findings generally improve within 1 week, and leukocytosis often resolves within 1 week.³

Notable Sequelae

Although AGEP typically is considered benign,² there have been reports of severe sequelae including death from a systemic inflammatory response and complications such as bacterial superinfection and sepsis.^6,7 Visceral involvement can be seen in up to 20% of AGEP patients, with systemic symptoms similar  to those seen in DRESS syndrome. Mortality has been reported in up to 5% of cases, mainly in patients with comorbidities and notable mucosal involvement.⁸ More severe disease can be seen in patients with known dermatologic disease, as AGEP can provoke an isomorphic phenomenon.⁹ Laboratory alterations typically seen in AGEP include neutrophilia, eosinophilia, and elevated liver enzymes.²

Follow-up Recommendations

Patients should be informed of the expected timeline for resolution and should be counseled on the possibility of rare systemic symptoms. Laboratory abnormalities should be monitored every 2 to 4 weeks until normalized.

DRESS SYNDROME

DRESS syndrome is characterized by a morbilliform eruption that can be accompanied by fever; eosinophilia; purpura; facial edema; lymphadenopathy; and liver, renal, or other organ dysfunction. DRESS syndrome most often presents within 8 weeks of exposure to a causative drug.^10,11 The most common causative agents are anticonvulsants, antimicrobials, and allopurinol.¹² Treatment includes topical corticosteroids and systemic corticosteroids for internal organ involvement.¹⁰

Short-term Sequelae

Several potential sequelae may occur within 6 months of resolution of DRESS syndrome, resulting from both the ADR itself and/or systemic corticosteroids that often are required for treatment.¹³ Complications secondary to herpesviruses have been reported.¹⁴ Cases of cytomegalovirus-induced gastric ulcers can lead to gastrointestinal tract bleeds.¹⁵

Infections including Cryptococcus species and herpes zoster also have been reported.¹⁶ Patients, particularly those treated with systemic corticosteroids, should be monitored with close follow-up for infectious complications and treatment-related adverse effects.¹³

Long-term Sequelae

Endocrine
Thyroid gland abnormalities secondary to DRESS syndrome include Graves disease and Hashimoto disease as well as variations in biomarkers including elevated free thyroxine and low and elevated thyroid-stimulating hormone levels.^16,17 Type 1 diabetes mellitus also has been seen after DRESS syndrome, developing within the first 10 months after onset with unknown pathogenesis.¹⁸

Autoimmune
Other reported sequelae of DRESS syndrome include elevated antinuclear antibodies with possible development into systemic lupus erythematosus, autoimmune hemolytic anemia, vitiligo, and rheumatoid arthritis.^11,16 Symptoms may be exacerbated in patients with preexisting autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and patients with preexisting renal disease are at an increased risk for requiring lifelong hemodialysis after DRESS syndrome.¹⁶

Other
Studies have demonstrated that pneumonia, thrombosis, and alopecia can be complications of DRESS syndrome.^11,16 Psychiatric disturbances including fear of taking new medications, anxiety, and depression also have been reported.¹⁹ Children with DRESS syndrome may develop vitiligo, alopecia, sclerodermatous lesions, photophobia, uveitis, and Vogt-Koyanagi-Harada disease.¹⁷

Follow-up Recommendations

It is important to inform patients of both the potential short-term and long-term sequelae of DRESS syndrome, including those associated with treatment. A thorough review of systems should be performed at each visit, along with laboratory evaluation including a complete blood cell count with differential and liver function testing every 1 to 2 weeks after discharge until normalized, with monthly monitoring of glucose, thyroid-stimulating hormone, and free thyroxine levels for 3 months after discharge.

STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS

Stevens-Johnson syndrome/toxic epidermal necrolysis are severe ADRs that present with dusky violaceous macules. Inciting medications include nonsteroidal anti-inflammatory drugs, allopurinol, antibiotics, and anticonvulsants, and symptoms begin 1 to 3 weeks after medication exposure.¹² Initially, the lesions often begin on the trunk and can progress to full-body erythema and exfoliation with a necrotic epidermis and mucosal involvement.^12,20

Notable Sequelae

Cutaneous
Chronic eczema can present at any time and can vary in severity in SJS/TEN patients.²¹ Xerosis and pruritus can be treated with emollients.¹¹ Dyschromia is common. Hypertrophic and keloidal scarring can result from surgical debridement and are best prevented with the use of nonadherent dressings.²² Nail changes such as anonychia, dystrophy, longitudinal ridges, and pterygium also are seen, and topical steroids can be helpful. Other reported dermatologic sequelae include dyschromia and eruption of ectopic sebaceous glands.^21,22

Ocular
Ocular sequelae include dry eyes, photophobia, symblepharon, corneal scarring, corneal neovascularization, corneal xerosis, trichiasis, reduced visual acuity, blindness, and subconjunctival fibrosis. The most common sequelae are bilateral conjunctivitis and corneal ulcerations.^22,23 Early and regular ophthalmologic follow-up is recommended, as SJS/TEN-induced blindness can result from delayed therapy, destroying corneal stem cells.²¹ Amniotic membrane transplantation replaces the damaged corneal membrane, which may reduce corneal inflammation.²⁴

Chronic dry eye syndrome can recur for years after SJS/TEN resolves and progresses over time.²² Frequent use of nonpreserved artificial tears and salivary gland transplantation can be helpful.²⁴ Unfortunately, ocular disease may develop months after discharge; therefore, it is recommended that dermatologists ask all SJS/TEN patients about ocular symptoms in follow-up visits. If ocular involvement was present initially, patients should be followed by ophthalmology for at least 1 year after discharge.²³

Genitourinary
Genitourinary sequelae in SJS/TEN include adhesions, particularly in the female urethra and vaginal opening; vaginal adenosis; vulvovaginal endometriosis; and persistent genital ulcerations most commonly reported in females.²² Prompt inpatient gynecologic or urologic consultation is critical to reduce these potentially permanent outcomes. Topical corticosteroid therapy is recommended in the acute phase.²²

Psychologic
Posttraumatic stress disorder may occur in patients with SJS/TEN. One study showed that 23% (7/30) of patients had posttraumatic stress disorder 6 months after hospitalization for SJS/TEN. The investigators recommended routine psychiatric assessment in the acute disease period and for at least 1 year after discharge.²⁵

Pulmonary, Gastrointestinal, and Renal
Interstitial pneumonia and obliterative bronchitis/bronchiolitis can be caused by SJS/TEN. Interstitial pneumonia tends to occur during the acute course, while obliterative airway disease manifests after resolution of SJS/TEN.^21,22 Abnormal pulmonary function testing can be seen in more than half of SJS/TEN patients 2 months after the ADR.²² Gastrointestinal sequelae include esophageal strictures, intestinal ulceration, and cholestasis.²² Renal sequelae include acute kidney injury and glomerulonephritis, which may be secondary to the volume loss seen in SJS/TEN but may be irreversible.²¹

Special Populations
A correlation with infertility in women has been documented in patients with SJS/TEN; thus, follow-up with obstetrics and gynecology is recommended in women of child-bearing potential. The most considerable risk in pregnant women with SJS/TEN is premature birth, and mucosal necrosis of SJS/TEN can impair vaginal delivery.²⁶ Antiretrovirals can be a cause of SJS/TEN in the human immunodeficiency virus–positive population.²⁷ In those cases, it is best to discontinue the medication and find an alternative.

Risk factors for children can be different and can include viral and febrile illnesses as well as mycoplasma infection.²⁸ Children also can be at an increased risk for poor ocular outcomes, such as permanent deficiency in visual acuity and blindness.²⁹

Follow-up Recommendations

Patients should be counseled regarding sequelae and the multisystem nature of SJS/TEN. Inpatient referrals should be given as needed. It is important to watch for ocular symptoms for 1 year after SJS/TEN resolution. When ocular involvement is present, follow-up with ophthalmology is recommended within 1 month of discharge and then at the discretion of the ophthalmologist. Pulmonary function should be monitored for 1 year after SJS/TEN, starting 1 month after discharge and then at the discretion of the pulmonologist. Patients also should be screened for psychologic sequelae for at least 1 year after discharge.

FINAL THOUGHTS

Adverse drug reactions are notable causes of inpatient hospitalization and may lead to considerable sequelae. These ADRs range in severity from more common and benign maculopapular exanthems to severe multiorgan ADRs such as DRESS syndrome and SJS/TEN.

In AGEP, it is important to monitor patients with preexisting dermatologic diseases and to screen for visceral involvement. DRESS syndrome has the potential to cause immune dysregulation and variable long-term adverse sequelae, both from the disease itself and from corticosteroid therapy. Mucocutaneous sequelae of SJS/TEN can potentially affect a patient’s cutaneous, ocular, genitourinary, mental, pulmonary, gastrointestinal, and renal health.

The baseline recommendations provided here warrant more frequent monitoring if the findings and symptoms are severe. In all of these cases, if a causative medication is identified, it should be added to the patient’s allergy list and the patient should be counseled extensively to avoid this medication and other medications in the same class. If a single agent cannot be identified, referrals for patch testing may be of some utility, particularly in AGEP and DRESS syndrome.^30,31

As systemic therapies for advanced melanoma increase, some historical prognostic factors continue to hold true while refined and novel risk factors are emerging, according to the results of three studies published in JAMA Dermatology.

Among the most prominent findings of those studies are that ulceration, mitotic index, and head and neck location in localized disease were predictive of early recurrence; time to recurrence was not associated with survival in unresectable stage IV melanoma; and certain gene markers may be linked with particular types of metastasis.

The first study, conducted by Lena A. von Schuckmann, MBBS, of the University of Queensland School of Public Health in Australia, and colleagues, evaluated the risk of early melanoma recurrence in patients with localized disease.

“With the introduction of targeted and immune therapies for treatment of metastatic melanoma, including possible adjuvant therapy, a detailed understanding of the risk of melanoma recurrence may assist clinicians to advise patients with a primary tumor at high risk of disease metastasis,” the researchers wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0440).

They conducted a prospective cohort study of 700 patients with high-risk, category T1b to T4b cutaneous melanoma, refined from an initial recruitment population of 1,254 individuals. Using self-administered patient questionnaires in conjunction with histologic, imaging, and clinical data over the course of 2 years, the investigators looked for factors that predicted recurrence.

Of 700 patients, 94 (13.4%) had disease recurrence, most often (70.2%) locoregional recurrence. Independent predictors of recurrence included mitotic rate greater than 3/mm², thickness, ulceration, and primary tumor location on the head or neck.

Patients with negative single lymph node biopsy (SLNB) were less likely to have recurrence than were those who did not undergo SLNB. Among 64 patients whose locoregional disease was excised, 37 (57.8%) were disease free at 2 years, whereas 7 patients (10.9%) had new locoregional disease and 20 patients (31.3%) developed a new distant recurrence.

“[O]ur data appear to support the recommendation for careful scar and regional skin and lymph node examination during patient follow-up,” the investigators concluded, alluding to the relatively high rate of locoregional recurrence. “Subsequent recurrences occurring at distant sites were more likely to involve multiple organs, which is consistent with other studies.”

The second melanoma article, investigating associations between time to relapse and survival, was authored by Anaïs Vallet, MD, of Hôpital Saint-Louis, Paris, and colleagues.

“Although the kinetics of metastatic disease seem to be correlated with patient survival, the first relapse is not predictable, and data from the literature on the topic are controversial,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0425). “We hypothesized that the progression of the metastatic disease would be associated with the time from primary excision to the first distant recurrence of melanoma.”

To test this hypothesis, the investigators analyzed data from 638 patients with unresectable stage III or IV melanoma. Inclusion required first-line treatment with chemotherapy, targeted therapies, or immunotherapies. The interval between primary excision and distant disease recurrence, measured as a categorical and continuous variable, was compared with overall survival and progression-free survival. The analysis revealed no associations between time to recurrence and either survival measure, even when stratified by treatment.

“Now that immunotherapies and targeted therapies have been approved in the adjuvant setting for patients with stage III disease, it would be interesting to analyze recurrence-free survival and [progression-free survival] in relapsing patients who previously received adjuvant therapies,” the investigators wrote.

The third study was conducted by Laura Calomarde-Rees, MD, of Instituto Valenciano de Oncología, València, Spain, and colleagues.

“Our aim was to identify risk factors associated with lymphatic (locoregional metastasis) or hematogenous (distant metastasis) progression because these have not been studied separately to date in patients with localized melanoma,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0069).

The retrospective study involved 1,177 patients with stage I to II melanoma. Multiple disease variables were evaluated in the context of each type of metastasis, including age, sex, tumor location, and others.

The investigators found locoregional spread was most often associated with vascular invasion (hazard ratio [HR], 3.2), greater Breslow thickness (HR, 5.4; thickness greater than 4 mm), acral location (HR, 2.4), head/neck location (HR, 1.7), and age greater than 55 years (HR, 1.9).

Distant metastasis was most often associated with greater Breslow thickness (HR, 10.4; thickness greater than 4 mm), TERT promoter mutations (HR, 2.9), BRAF mutations (HR, 1.9), and absence of regression (HR, 0.1).

“Risk factors for lymphatic and hematogenous metastasis differ,” the investigators concluded. “A greater understanding of the clinical, histopathologic, and molecular factors involved could help to identify patients with an increased risk of recurrence and guide the design of individualized follow-up programs and adjuvant targeted therapies.”

Dr. von Schuckmann and colleagues disclosed study funding from the National Health and Medical Research Council and other relationships with the Norwegian Cancer Society project. Dr. Vallet and colleagues reported study support from French National Cancer Institute, MSD, BMS, Roche, and Novartis; and additional relationships with Incyte, Amgen, Pfizer, and others. Dr. Calomarde-Rees and colleagues disclosed no conflicts of interest.

As systemic therapies for advanced melanoma increase, some historical prognostic factors continue to hold true while refined and novel risk factors are emerging, according to the results of three studies published in JAMA Dermatology.

Among the most prominent findings of those studies are that ulceration, mitotic index, and head and neck location in localized disease were predictive of early recurrence; time to recurrence was not associated with survival in unresectable stage IV melanoma; and certain gene markers may be linked with particular types of metastasis.

The first study, conducted by Lena A. von Schuckmann, MBBS, of the University of Queensland School of Public Health in Australia, and colleagues, evaluated the risk of early melanoma recurrence in patients with localized disease.

“With the introduction of targeted and immune therapies for treatment of metastatic melanoma, including possible adjuvant therapy, a detailed understanding of the risk of melanoma recurrence may assist clinicians to advise patients with a primary tumor at high risk of disease metastasis,” the researchers wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0440).

They conducted a prospective cohort study of 700 patients with high-risk, category T1b to T4b cutaneous melanoma, refined from an initial recruitment population of 1,254 individuals. Using self-administered patient questionnaires in conjunction with histologic, imaging, and clinical data over the course of 2 years, the investigators looked for factors that predicted recurrence.

Of 700 patients, 94 (13.4%) had disease recurrence, most often (70.2%) locoregional recurrence. Independent predictors of recurrence included mitotic rate greater than 3/mm², thickness, ulceration, and primary tumor location on the head or neck.

Patients with negative single lymph node biopsy (SLNB) were less likely to have recurrence than were those who did not undergo SLNB. Among 64 patients whose locoregional disease was excised, 37 (57.8%) were disease free at 2 years, whereas 7 patients (10.9%) had new locoregional disease and 20 patients (31.3%) developed a new distant recurrence.

“[O]ur data appear to support the recommendation for careful scar and regional skin and lymph node examination during patient follow-up,” the investigators concluded, alluding to the relatively high rate of locoregional recurrence. “Subsequent recurrences occurring at distant sites were more likely to involve multiple organs, which is consistent with other studies.”

The second melanoma article, investigating associations between time to relapse and survival, was authored by Anaïs Vallet, MD, of Hôpital Saint-Louis, Paris, and colleagues.

“Although the kinetics of metastatic disease seem to be correlated with patient survival, the first relapse is not predictable, and data from the literature on the topic are controversial,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0425). “We hypothesized that the progression of the metastatic disease would be associated with the time from primary excision to the first distant recurrence of melanoma.”

To test this hypothesis, the investigators analyzed data from 638 patients with unresectable stage III or IV melanoma. Inclusion required first-line treatment with chemotherapy, targeted therapies, or immunotherapies. The interval between primary excision and distant disease recurrence, measured as a categorical and continuous variable, was compared with overall survival and progression-free survival. The analysis revealed no associations between time to recurrence and either survival measure, even when stratified by treatment.

“Now that immunotherapies and targeted therapies have been approved in the adjuvant setting for patients with stage III disease, it would be interesting to analyze recurrence-free survival and [progression-free survival] in relapsing patients who previously received adjuvant therapies,” the investigators wrote.

The third study was conducted by Laura Calomarde-Rees, MD, of Instituto Valenciano de Oncología, València, Spain, and colleagues.

“Our aim was to identify risk factors associated with lymphatic (locoregional metastasis) or hematogenous (distant metastasis) progression because these have not been studied separately to date in patients with localized melanoma,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0069).

The retrospective study involved 1,177 patients with stage I to II melanoma. Multiple disease variables were evaluated in the context of each type of metastasis, including age, sex, tumor location, and others.

The investigators found locoregional spread was most often associated with vascular invasion (hazard ratio [HR], 3.2), greater Breslow thickness (HR, 5.4; thickness greater than 4 mm), acral location (HR, 2.4), head/neck location (HR, 1.7), and age greater than 55 years (HR, 1.9).

Distant metastasis was most often associated with greater Breslow thickness (HR, 10.4; thickness greater than 4 mm), TERT promoter mutations (HR, 2.9), BRAF mutations (HR, 1.9), and absence of regression (HR, 0.1).

“Risk factors for lymphatic and hematogenous metastasis differ,” the investigators concluded. “A greater understanding of the clinical, histopathologic, and molecular factors involved could help to identify patients with an increased risk of recurrence and guide the design of individualized follow-up programs and adjuvant targeted therapies.”

Dr. von Schuckmann and colleagues disclosed study funding from the National Health and Medical Research Council and other relationships with the Norwegian Cancer Society project. Dr. Vallet and colleagues reported study support from French National Cancer Institute, MSD, BMS, Roche, and Novartis; and additional relationships with Incyte, Amgen, Pfizer, and others. Dr. Calomarde-Rees and colleagues disclosed no conflicts of interest.

As systemic therapies for advanced melanoma increase, some historical prognostic factors continue to hold true while refined and novel risk factors are emerging, according to the results of three studies published in JAMA Dermatology.

Among the most prominent findings of those studies are that ulceration, mitotic index, and head and neck location in localized disease were predictive of early recurrence; time to recurrence was not associated with survival in unresectable stage IV melanoma; and certain gene markers may be linked with particular types of metastasis.

The first study, conducted by Lena A. von Schuckmann, MBBS, of the University of Queensland School of Public Health in Australia, and colleagues, evaluated the risk of early melanoma recurrence in patients with localized disease.

“With the introduction of targeted and immune therapies for treatment of metastatic melanoma, including possible adjuvant therapy, a detailed understanding of the risk of melanoma recurrence may assist clinicians to advise patients with a primary tumor at high risk of disease metastasis,” the researchers wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0440).

They conducted a prospective cohort study of 700 patients with high-risk, category T1b to T4b cutaneous melanoma, refined from an initial recruitment population of 1,254 individuals. Using self-administered patient questionnaires in conjunction with histologic, imaging, and clinical data over the course of 2 years, the investigators looked for factors that predicted recurrence.

Of 700 patients, 94 (13.4%) had disease recurrence, most often (70.2%) locoregional recurrence. Independent predictors of recurrence included mitotic rate greater than 3/mm², thickness, ulceration, and primary tumor location on the head or neck.

Patients with negative single lymph node biopsy (SLNB) were less likely to have recurrence than were those who did not undergo SLNB. Among 64 patients whose locoregional disease was excised, 37 (57.8%) were disease free at 2 years, whereas 7 patients (10.9%) had new locoregional disease and 20 patients (31.3%) developed a new distant recurrence.

“[O]ur data appear to support the recommendation for careful scar and regional skin and lymph node examination during patient follow-up,” the investigators concluded, alluding to the relatively high rate of locoregional recurrence. “Subsequent recurrences occurring at distant sites were more likely to involve multiple organs, which is consistent with other studies.”

The second melanoma article, investigating associations between time to relapse and survival, was authored by Anaïs Vallet, MD, of Hôpital Saint-Louis, Paris, and colleagues.

“Although the kinetics of metastatic disease seem to be correlated with patient survival, the first relapse is not predictable, and data from the literature on the topic are controversial,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0425). “We hypothesized that the progression of the metastatic disease would be associated with the time from primary excision to the first distant recurrence of melanoma.”

To test this hypothesis, the investigators analyzed data from 638 patients with unresectable stage III or IV melanoma. Inclusion required first-line treatment with chemotherapy, targeted therapies, or immunotherapies. The interval between primary excision and distant disease recurrence, measured as a categorical and continuous variable, was compared with overall survival and progression-free survival. The analysis revealed no associations between time to recurrence and either survival measure, even when stratified by treatment.

“Now that immunotherapies and targeted therapies have been approved in the adjuvant setting for patients with stage III disease, it would be interesting to analyze recurrence-free survival and [progression-free survival] in relapsing patients who previously received adjuvant therapies,” the investigators wrote.

The third study was conducted by Laura Calomarde-Rees, MD, of Instituto Valenciano de Oncología, València, Spain, and colleagues.

“Our aim was to identify risk factors associated with lymphatic (locoregional metastasis) or hematogenous (distant metastasis) progression because these have not been studied separately to date in patients with localized melanoma,” they wrote (JAMA Dermatol. 2019 May 1. doi: 10.1001/jamadermatol.2019.0069).

The retrospective study involved 1,177 patients with stage I to II melanoma. Multiple disease variables were evaluated in the context of each type of metastasis, including age, sex, tumor location, and others.

The investigators found locoregional spread was most often associated with vascular invasion (hazard ratio [HR], 3.2), greater Breslow thickness (HR, 5.4; thickness greater than 4 mm), acral location (HR, 2.4), head/neck location (HR, 1.7), and age greater than 55 years (HR, 1.9).

Distant metastasis was most often associated with greater Breslow thickness (HR, 10.4; thickness greater than 4 mm), TERT promoter mutations (HR, 2.9), BRAF mutations (HR, 1.9), and absence of regression (HR, 0.1).

“Risk factors for lymphatic and hematogenous metastasis differ,” the investigators concluded. “A greater understanding of the clinical, histopathologic, and molecular factors involved could help to identify patients with an increased risk of recurrence and guide the design of individualized follow-up programs and adjuvant targeted therapies.”

Dr. von Schuckmann and colleagues disclosed study funding from the National Health and Medical Research Council and other relationships with the Norwegian Cancer Society project. Dr. Vallet and colleagues reported study support from French National Cancer Institute, MSD, BMS, Roche, and Novartis; and additional relationships with Incyte, Amgen, Pfizer, and others. Dr. Calomarde-Rees and colleagues disclosed no conflicts of interest.

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

agallegos@mdedge.com

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

agallegos@mdedge.com

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

agallegos@mdedge.com

The Trump administration is asking an appeals court to strike down the entire Affordable Care Act (ACA), a shift from the administration’s earlier stance that had supported some elements of the law in a lawsuit challenging its constitutionality.

jsmith/iStockphoto

In a brief issued May 1 to the 5th U.S. Court of Appeals, Justice Department attorneys wrote that provisions of the health care law cannot be severed from the whole and thus, the entire ACA should be ruled invalid. The Justice Department did not specify why it changed its position in Texas v. United States, except to say the new opinion came upon further consideration and review of the lower court’s opinion.

Texas v. United States, filed by a group of 18 Republican state attorneys general and two individuals in 2018, centers on whether the ACA should stand if provisions of the law are no longer valid. The plaintiffs argue that, because budget legislation in 2017 zeroed out the penalties associated with the ACA’s individual mandate, the mandate is invalid. If the mandate is severed, the entire ACA should be struck down, the plaintiffs said. The Justice Department declined to fully defend the law and so 16 Democratic state attorneys general intervened to defend the ACA in the case.

In an initial brief, the Trump administration agreed that the mandate was unconstitutional and should be parsed. Attorneys for the administration wrote that, if the mandate is found unconstitutional, the court should also consider finding two other provisions – the guaranteed issue and community rating requirements – of the ACA invalid. Guaranteed issue refers to insurers in the individual market offering coverage to all citizens, regardless of preexisting conditions, while community rating refers to charging equal premiums to every patient, no matter their past health status. At the time however, the Trump administration said the remainder of the ACA can stand without the three linked provisions.

In December 2018, a district court declared the entire ACA to be invalid, a decision immediately appealed to the 5th Circuit by the Democratic attorneys general. The circuit court froze the case in light of the federal government’s partial shutdown at the time. The case remains on hold.

The Trump administration’s new stance that the entire ACA should be declared unconstitutional was widely condemned by Democratic legislators.

“If President Trump wins against health care, families lose,” Sen. Patty Murray (D-Wash.) tweeted May 1. “They’ll lose their health care, lose protections for preexisting conditions, and lose to insurance companies who will have free rein to deny coverage and leave patients to shoulder high costs.”

The White House had not issued a statement about its new position in the case at press time.

In a separate brief filed with the appeals court on May 1, Texas Attorney General Ken Paxton, a Republican plaintiff in the case, reiterated his side’s opposition to the ACA and called for the court to uphold the lower court’s ruling striking down the law.

“Congress meant for the individual mandate to be the centerpiece of Obamacare,” Attorney General Paxton said in a statement. “Without the constitutional justification for the centerpiece, the law must go down. Obamacare is a failed social experiment. The sooner it is invalidated, the better, so each state can decide what type of health care system it wants and how best to provide for those with preexisting conditions, which is federalism that the founders intended.”

Timothy Jost, a health law professor at Washington and Lee University in Lexington, Va., said that administration’s revised position in Texas v. U.S. won’t have much impact on the case.

“The Department of Justice brief doesn’t change anything,” Mr. Jost said in an interview. “They basically make the same arguments that the individual plaintiffs and the state plaintiffs do as to the major issues in the case.

However, Mr. Jost said that the administration’s brief sounds confused and reads almost like two separate briefs. On one hand, the Justice Department argues that the entire ACA should be invalid because the mandate cannot be severed. On the other hand, the agency argues that court relief should be “limited only to those provisions that actually injure the individual plaintiffs.” Specifically, Justice Department attorneys indicate that health care fraud and abuse protections in the ACA should be preserved.

“It looks like they kind of want to have their cake and eat it, too,” Mr. Jost said. “They want to preserve the provisions of the ACA they like, but not the sections that they don’t like. That could serve to confuse the issue for the appellate court.”

Oral arguments in the case are slated for July with a possible decision expected by the end of 2019. Legal analysts expect the losing side to appeal to the Supreme Court.

agallegos@mdedge.com

The Trump administration is asking an appeals court to strike down the entire Affordable Care Act (ACA), a shift from the administration’s earlier stance that had supported some elements of the law in a lawsuit challenging its constitutionality.

jsmith/iStockphoto

In a brief issued May 1 to the 5th U.S. Court of Appeals, Justice Department attorneys wrote that provisions of the health care law cannot be severed from the whole and thus, the entire ACA should be ruled invalid. The Justice Department did not specify why it changed its position in Texas v. United States, except to say the new opinion came upon further consideration and review of the lower court’s opinion.

Texas v. United States, filed by a group of 18 Republican state attorneys general and two individuals in 2018, centers on whether the ACA should stand if provisions of the law are no longer valid. The plaintiffs argue that, because budget legislation in 2017 zeroed out the penalties associated with the ACA’s individual mandate, the mandate is invalid. If the mandate is severed, the entire ACA should be struck down, the plaintiffs said. The Justice Department declined to fully defend the law and so 16 Democratic state attorneys general intervened to defend the ACA in the case.

In an initial brief, the Trump administration agreed that the mandate was unconstitutional and should be parsed. Attorneys for the administration wrote that, if the mandate is found unconstitutional, the court should also consider finding two other provisions – the guaranteed issue and community rating requirements – of the ACA invalid. Guaranteed issue refers to insurers in the individual market offering coverage to all citizens, regardless of preexisting conditions, while community rating refers to charging equal premiums to every patient, no matter their past health status. At the time however, the Trump administration said the remainder of the ACA can stand without the three linked provisions.

In December 2018, a district court declared the entire ACA to be invalid, a decision immediately appealed to the 5th Circuit by the Democratic attorneys general. The circuit court froze the case in light of the federal government’s partial shutdown at the time. The case remains on hold.

The Trump administration’s new stance that the entire ACA should be declared unconstitutional was widely condemned by Democratic legislators.

“If President Trump wins against health care, families lose,” Sen. Patty Murray (D-Wash.) tweeted May 1. “They’ll lose their health care, lose protections for preexisting conditions, and lose to insurance companies who will have free rein to deny coverage and leave patients to shoulder high costs.”

The White House had not issued a statement about its new position in the case at press time.

In a separate brief filed with the appeals court on May 1, Texas Attorney General Ken Paxton, a Republican plaintiff in the case, reiterated his side’s opposition to the ACA and called for the court to uphold the lower court’s ruling striking down the law.

“Congress meant for the individual mandate to be the centerpiece of Obamacare,” Attorney General Paxton said in a statement. “Without the constitutional justification for the centerpiece, the law must go down. Obamacare is a failed social experiment. The sooner it is invalidated, the better, so each state can decide what type of health care system it wants and how best to provide for those with preexisting conditions, which is federalism that the founders intended.”

Timothy Jost, a health law professor at Washington and Lee University in Lexington, Va., said that administration’s revised position in Texas v. U.S. won’t have much impact on the case.

“The Department of Justice brief doesn’t change anything,” Mr. Jost said in an interview. “They basically make the same arguments that the individual plaintiffs and the state plaintiffs do as to the major issues in the case.

However, Mr. Jost said that the administration’s brief sounds confused and reads almost like two separate briefs. On one hand, the Justice Department argues that the entire ACA should be invalid because the mandate cannot be severed. On the other hand, the agency argues that court relief should be “limited only to those provisions that actually injure the individual plaintiffs.” Specifically, Justice Department attorneys indicate that health care fraud and abuse protections in the ACA should be preserved.

“It looks like they kind of want to have their cake and eat it, too,” Mr. Jost said. “They want to preserve the provisions of the ACA they like, but not the sections that they don’t like. That could serve to confuse the issue for the appellate court.”

Oral arguments in the case are slated for July with a possible decision expected by the end of 2019. Legal analysts expect the losing side to appeal to the Supreme Court.

agallegos@mdedge.com

The Trump administration is asking an appeals court to strike down the entire Affordable Care Act (ACA), a shift from the administration’s earlier stance that had supported some elements of the law in a lawsuit challenging its constitutionality.

jsmith/iStockphoto

In a brief issued May 1 to the 5th U.S. Court of Appeals, Justice Department attorneys wrote that provisions of the health care law cannot be severed from the whole and thus, the entire ACA should be ruled invalid. The Justice Department did not specify why it changed its position in Texas v. United States, except to say the new opinion came upon further consideration and review of the lower court’s opinion.

Texas v. United States, filed by a group of 18 Republican state attorneys general and two individuals in 2018, centers on whether the ACA should stand if provisions of the law are no longer valid. The plaintiffs argue that, because budget legislation in 2017 zeroed out the penalties associated with the ACA’s individual mandate, the mandate is invalid. If the mandate is severed, the entire ACA should be struck down, the plaintiffs said. The Justice Department declined to fully defend the law and so 16 Democratic state attorneys general intervened to defend the ACA in the case.

In an initial brief, the Trump administration agreed that the mandate was unconstitutional and should be parsed. Attorneys for the administration wrote that, if the mandate is found unconstitutional, the court should also consider finding two other provisions – the guaranteed issue and community rating requirements – of the ACA invalid. Guaranteed issue refers to insurers in the individual market offering coverage to all citizens, regardless of preexisting conditions, while community rating refers to charging equal premiums to every patient, no matter their past health status. At the time however, the Trump administration said the remainder of the ACA can stand without the three linked provisions.

In December 2018, a district court declared the entire ACA to be invalid, a decision immediately appealed to the 5th Circuit by the Democratic attorneys general. The circuit court froze the case in light of the federal government’s partial shutdown at the time. The case remains on hold.

The Trump administration’s new stance that the entire ACA should be declared unconstitutional was widely condemned by Democratic legislators.

“If President Trump wins against health care, families lose,” Sen. Patty Murray (D-Wash.) tweeted May 1. “They’ll lose their health care, lose protections for preexisting conditions, and lose to insurance companies who will have free rein to deny coverage and leave patients to shoulder high costs.”

The White House had not issued a statement about its new position in the case at press time.

In a separate brief filed with the appeals court on May 1, Texas Attorney General Ken Paxton, a Republican plaintiff in the case, reiterated his side’s opposition to the ACA and called for the court to uphold the lower court’s ruling striking down the law.

“Congress meant for the individual mandate to be the centerpiece of Obamacare,” Attorney General Paxton said in a statement. “Without the constitutional justification for the centerpiece, the law must go down. Obamacare is a failed social experiment. The sooner it is invalidated, the better, so each state can decide what type of health care system it wants and how best to provide for those with preexisting conditions, which is federalism that the founders intended.”

Timothy Jost, a health law professor at Washington and Lee University in Lexington, Va., said that administration’s revised position in Texas v. U.S. won’t have much impact on the case.

“The Department of Justice brief doesn’t change anything,” Mr. Jost said in an interview. “They basically make the same arguments that the individual plaintiffs and the state plaintiffs do as to the major issues in the case.

However, Mr. Jost said that the administration’s brief sounds confused and reads almost like two separate briefs. On one hand, the Justice Department argues that the entire ACA should be invalid because the mandate cannot be severed. On the other hand, the agency argues that court relief should be “limited only to those provisions that actually injure the individual plaintiffs.” Specifically, Justice Department attorneys indicate that health care fraud and abuse protections in the ACA should be preserved.

“It looks like they kind of want to have their cake and eat it, too,” Mr. Jost said. “They want to preserve the provisions of the ACA they like, but not the sections that they don’t like. That could serve to confuse the issue for the appellate court.”

Oral arguments in the case are slated for July with a possible decision expected by the end of 2019. Legal analysts expect the losing side to appeal to the Supreme Court.

agallegos@mdedge.com

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

sdominick/iStock/Getty Images

“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

sdominick/iStock/Getty Images

“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

An opioid prescription management program implemented at the Cleveland Clinic has led to a reduction in the number of narcotics prescribed to patients after breast surgery, according to research presented in a recent webcast from the annual meeting of the American Society of Breast Surgeons.

sdominick/iStock/Getty Images

“The opioid epidemic has become a critical issue, and narcotic abuse has continued to rise,” Stephanie Valente, DO, FACS, from the Cleveland Clinic, said in her presentation. “Excess narcotic prescriptions may be contributing to this opioid epidemic,” and there are no current narcotic prescribing guidelines for patients after breast surgery, she said. In addition, studies have shown surgeons can overestimate the number of opioid pills a patient needs after surgery for pain control, and any excess pills are at risk of being stolen or inappropriately used, she added.

Dr. Valente and colleagues performed a baseline evaluation of narcotic pills prescribed by surgeons at the Cleveland Clinic for patients who have undergone excisional biopsy or lumpectomy, mastectomy, and mastectomy with reconstruction. They found the median number of narcotics prescribed were 15 pills for excisional biopsy or lumpectomy patients, 20 pills for mastectomy patients and 28 pills for mastectomy with reconstruction patients.

The researchers sought to lower those numbers, and created a departmental change in which they decreased the median number of pills prescribed at discharge from 15 pills to 10 pills for excisional biopsy or lumpectomy patients and from 28 pills to 25 pills for patients who undergo mastectomy with reconstruction. They then examined 100 consecutive patients after a 3-month implementation period to determine whether prescribing numbers had changed and found the surgeons adhered to the prescribing guidelines, which resulted in a statistically significant reduction in median opioid pills prescribed for excisional biopsy or lumpectomy (P less than .01) and mastectomy with reconstruction patients (P less than .01).

“After their departmental plan change, we observed that, as planned, a statistically significant decrease in prescribing practices amongst surgeons was able to be performed, showing that surgeons were able to adhere to these new prescribing practices,” said Dr. Valente.

When they examined the number of pills patients reported they used after surgery, they found excisional biopsy or lumpectomy patients took an average of 1 pill, mastectomy patients took an average of 3 pills, and mastectomy with reconstruction patients took an average of 18 pills. “These were all statistically much less than what was being prescribed even after our purposeful reduction,” said Dr. Valente.

In the study, 40% of patients who underwent breast surgery overall reported that they did not have any postoperative narcotic use at all, with the least narcotic use seen among patients who underwent excisional biopsy or lumpectomy.

“Further directions for opiate reduction can include evaluation of the impact of type and amount of local anesthetic given intraoperatively, and the amount of narcotics used postoperatively … to identify patient factors that contribute to the low narcotic usage postoperatively, and finally, to figure out how to maximize the benefit of adding a formal ERAS [enhanced recovery after surgery] protocol to further reduce patient needs for as many narcotic pills,” said Dr. Valente.

Dr. Valente had no disclosures.

Health care professionals may not be compelled to provide medical care, including abortion services or even referrals, if they object on religious or moral grounds under a federal regulation finalized May 2.

The regulation also requires health care entities that receive federal funding to alert their employees to their federal conscience rights.

This final rule “replaces a 2011 rule that has proven inadequate, and ensures that HHS implements the full set of tools appropriate for enforcing the conscience protections passed by Congress,” HHS officials said in a statement. “These federal laws protect providers, individuals, and other health care entities from having to provide, participate in, pay for, provide coverage of, or refer for, services such as abortion, sterilization, or assisted suicide. It also includes conscience protections with respect to advance directives.”

The regulation was first proposed in January 2018, shortly after the formation of the Conscience and Religious Freedom Division within the HHS Office of Civil Rights (OCR).

Application of the regulation extends beyond the clinic and hospital. The regulation notes that, on a case-by-case basis, those providing emergency services such as EMTs or even ambulance drivers could be protected should they choose to exercise their conscience and not provide services based on their religious beliefs.

“With this final rule, the Department seeks to educate protected entities and covered entities as to their legal rights and obligations; to encourage individuals and organizations with religious beliefs or moral convictions to enter, or remain in, the health care industry; and to prevent others from being dissuaded from filing complaints due to prior OCR complaint resolutions or sub-regulatory guidance that no reflect the views of the Department,” according to the regulation.

HHS officials denied accusations that the regulation puts the needs of providers over those of patients.

By “protecting a diversity of beliefs among health care providers, these protections ensure that options are available to patients who desire, and would feel most comfortable with, a provider whose religious beliefs or moral convictions match their own. Even where a patient and provider do not share the same religious beliefs or moral convictions, it is not necessarily the case that patients would want providers to be forced to violate their religious beliefs or moral convictions,” according to the regulation.

However, the American Civil Liberties Union and others see the new regulation as license to discriminate.

“Once again, this administration shows itself to be determined to use religious liberty to harm communities it deems less worthy of equal treatment under the law,” Louise Melling, ACLU deputy legal director, said in a statement. “This rule threatens to prevent people from accessing critical medical care and may endanger people’s lives. Religious liberty is a fundamental right, but it does not include the right to discriminate or harm others. Denying patients health care is not religious liberty. Discriminating against patients based on their gender or gender expression is not religious liberty. Medical standards, not religious beliefs, should guide medical care.”

The regulation does not yet have a scheduled publication date in the Federal Register, nor has it been posted as a preview document on the publication’s website. It will become effective 60 days after publication.

gtwachtman@mdedge.com

Health care professionals may not be compelled to provide medical care, including abortion services or even referrals, if they object on religious or moral grounds under a federal regulation finalized May 2.

The regulation also requires health care entities that receive federal funding to alert their employees to their federal conscience rights.

This final rule “replaces a 2011 rule that has proven inadequate, and ensures that HHS implements the full set of tools appropriate for enforcing the conscience protections passed by Congress,” HHS officials said in a statement. “These federal laws protect providers, individuals, and other health care entities from having to provide, participate in, pay for, provide coverage of, or refer for, services such as abortion, sterilization, or assisted suicide. It also includes conscience protections with respect to advance directives.”

The regulation was first proposed in January 2018, shortly after the formation of the Conscience and Religious Freedom Division within the HHS Office of Civil Rights (OCR).

Application of the regulation extends beyond the clinic and hospital. The regulation notes that, on a case-by-case basis, those providing emergency services such as EMTs or even ambulance drivers could be protected should they choose to exercise their conscience and not provide services based on their religious beliefs.

“With this final rule, the Department seeks to educate protected entities and covered entities as to their legal rights and obligations; to encourage individuals and organizations with religious beliefs or moral convictions to enter, or remain in, the health care industry; and to prevent others from being dissuaded from filing complaints due to prior OCR complaint resolutions or sub-regulatory guidance that no reflect the views of the Department,” according to the regulation.

HHS officials denied accusations that the regulation puts the needs of providers over those of patients.

By “protecting a diversity of beliefs among health care providers, these protections ensure that options are available to patients who desire, and would feel most comfortable with, a provider whose religious beliefs or moral convictions match their own. Even where a patient and provider do not share the same religious beliefs or moral convictions, it is not necessarily the case that patients would want providers to be forced to violate their religious beliefs or moral convictions,” according to the regulation.

However, the American Civil Liberties Union and others see the new regulation as license to discriminate.

“Once again, this administration shows itself to be determined to use religious liberty to harm communities it deems less worthy of equal treatment under the law,” Louise Melling, ACLU deputy legal director, said in a statement. “This rule threatens to prevent people from accessing critical medical care and may endanger people’s lives. Religious liberty is a fundamental right, but it does not include the right to discriminate or harm others. Denying patients health care is not religious liberty. Discriminating against patients based on their gender or gender expression is not religious liberty. Medical standards, not religious beliefs, should guide medical care.”

The regulation does not yet have a scheduled publication date in the Federal Register, nor has it been posted as a preview document on the publication’s website. It will become effective 60 days after publication.

gtwachtman@mdedge.com

Health care professionals may not be compelled to provide medical care, including abortion services or even referrals, if they object on religious or moral grounds under a federal regulation finalized May 2.

The regulation also requires health care entities that receive federal funding to alert their employees to their federal conscience rights.

This final rule “replaces a 2011 rule that has proven inadequate, and ensures that HHS implements the full set of tools appropriate for enforcing the conscience protections passed by Congress,” HHS officials said in a statement. “These federal laws protect providers, individuals, and other health care entities from having to provide, participate in, pay for, provide coverage of, or refer for, services such as abortion, sterilization, or assisted suicide. It also includes conscience protections with respect to advance directives.”

The regulation was first proposed in January 2018, shortly after the formation of the Conscience and Religious Freedom Division within the HHS Office of Civil Rights (OCR).

Application of the regulation extends beyond the clinic and hospital. The regulation notes that, on a case-by-case basis, those providing emergency services such as EMTs or even ambulance drivers could be protected should they choose to exercise their conscience and not provide services based on their religious beliefs.

“With this final rule, the Department seeks to educate protected entities and covered entities as to their legal rights and obligations; to encourage individuals and organizations with religious beliefs or moral convictions to enter, or remain in, the health care industry; and to prevent others from being dissuaded from filing complaints due to prior OCR complaint resolutions or sub-regulatory guidance that no reflect the views of the Department,” according to the regulation.

HHS officials denied accusations that the regulation puts the needs of providers over those of patients.

By “protecting a diversity of beliefs among health care providers, these protections ensure that options are available to patients who desire, and would feel most comfortable with, a provider whose religious beliefs or moral convictions match their own. Even where a patient and provider do not share the same religious beliefs or moral convictions, it is not necessarily the case that patients would want providers to be forced to violate their religious beliefs or moral convictions,” according to the regulation.

However, the American Civil Liberties Union and others see the new regulation as license to discriminate.

“Once again, this administration shows itself to be determined to use religious liberty to harm communities it deems less worthy of equal treatment under the law,” Louise Melling, ACLU deputy legal director, said in a statement. “This rule threatens to prevent people from accessing critical medical care and may endanger people’s lives. Religious liberty is a fundamental right, but it does not include the right to discriminate or harm others. Denying patients health care is not religious liberty. Discriminating against patients based on their gender or gender expression is not religious liberty. Medical standards, not religious beliefs, should guide medical care.”

The regulation does not yet have a scheduled publication date in the Federal Register, nor has it been posted as a preview document on the publication’s website. It will become effective 60 days after publication.

gtwachtman@mdedge.com

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

Medicare officials aim to shift the program’s focus from sickness to wellness with the introduction of two new primary care value-based payment care models.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.

“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.

TheaDesign/Thinkstock

The American Medical Association also voiced its support.

“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”

The American College of Physicians also noted their support of the new models.

“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits,” Robert McLean, MD, ACP president, said in a statement.

The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things.”

gtwachtman@mdedge.com

Medicare officials aim to shift the program’s focus from sickness to wellness with the introduction of two new primary care value-based payment care models.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.

“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.

TheaDesign/Thinkstock

The American Medical Association also voiced its support.

“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”

The American College of Physicians also noted their support of the new models.

“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits,” Robert McLean, MD, ACP president, said in a statement.

The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things.”

gtwachtman@mdedge.com

Medicare officials aim to shift the program’s focus from sickness to wellness with the introduction of two new primary care value-based payment care models.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

“We’re launching CMS Primary Cares, an initiative of two new payment models that will enroll a quarter or more of traditional Medicare beneficiaries and a quarter of providers in arrangements that pay for keeping patients healthy, rather than ordering procedures,” Alex Azar, secretary of Health and Human Services, said April 22 during a press conference.

“Today’s announcement creates innovation in primary care that has the potential to entirely transform our fee-for-service system – which is about 65% of the Medicare program – into one that drives value,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said during the press conference.

TheaDesign/Thinkstock

The American Medical Association also voiced its support.

“Providing adequate financial support for high-quality primary care must be an essential element of any strategy to improve the quality and affordability of our country’s health care system, Gerald E. Harmon, MD, immediate past chair of the AMA Board of Trustees, said in a statement. “Many primary care physicians have been struggling to deliver the care their patients need and to financially sustain their practices under current Medicare payments. The new primary care payment models announced today will provide practices with more resources and more flexibility to deliver the highest-quality care to their patients.”

The American College of Physicians also noted their support of the new models.

“ACP is optimistic that the new models will emphasize the important role primary care plays in value-based care delivery, that models are voluntary and have a range of risk options, and that practices should use population health management data to reap potential benefits,” Robert McLean, MD, ACP president, said in a statement.

The success and viability of these models will depend on the extent that they are supported by payers in addition to Medicare and Medicaid, are adequately adjusted for differences in the risk and health status of patients seen by each practice, are provided predictable and adequate payments to support and sustain practices (especially smaller independent ones), are appropriately scaled for the financial risk expected of a practice, are provided meaningful and timely data to support improvement, and are truly able to reduce administrative tasks and costs, among other things.”

gtwachtman@mdedge.com

ATLANTA – Combination entinostat and pembrolizumab showed promising activity in a phase 2 study of non–small cell lung cancer patients who progressed on or after anti-programmed death-ligand 1 (PD-L1) therapy, and new analyses have identified gene signatures associated with treatment response.

Gene set analysis in tumors from 43 of the patients – 4 responders and 39 nonresponders – who participated in the open-label ENCORE-601 study revealed that Myc gene signaling was enriched in responders vs. nonresponders, Suresh S. Ramalingam, MD, said at the annual meeting of the American Association for Cancer Research.

High Myc gene activity is known from previous studies to be associated with response to immune checkpoint inhibition, and this has been attributed to high PD-L1 expression, decrease in interferon signatures, and exclusion of lymphocytes, he noted.

“And we know from other publications that entinostat is known to decrease Myc activity,” he said. “Therefore, our putative hypothesis at this time – albeit on a small set of patients – is that for patients with baseline high Myc activity, when they have developed resistance to PD-1 or PD-L1 inhibition ... giving them entinostat drives down the Myc activity and results in a change in the tumor microenvironment to one where immune checkpoint inhibition could be rendered effective.”


Patients from ENCORE-601 also were evaluated by baseline circulating classical monocyte levels as prior findings showed improved overall survival and progression-free survival (PFS) in melanoma patients with higher vs. lower counts, Dr. Ramalingam explained.

The overall response rate (ORR) in those with baseline levels above the median (MHi, 11 patients) was 21.1% vs. 6.5% in those with levels below the median (MLo, 32 patients); median PFS was 4.7 vs. 2.7 months in the MHi and MLo groups, respectively, said Dr. Ramalingam of Winship Cancer Institute, Emory University, Atlanta.

ENCORE-601 included 76 subjects who received entinostat at a dose of 5 mg per week plus intravenous pembrolizumab at 200 mg every 3 weeks. The confirmed ORR with treatment in 72 efficacy-evaluable patients was 10%, with an additional 50% of patients having stable disease. The median duration of response was 8 months, and median PFS was 2.8 months.

Top-line results from the study, which was undertaken based in part on preclinical data showing synergy between the oral class 1-selective histone deacetylase inhibitor entinostat and anti-PD-1 inhibition, were presented at the 2018 World Conference on Lung Cancer, and the current findings represent secondary outcome measures involving analyses in pretreatment tumor samples from patients with sufficient RNA yield for analysis.


The data may provide a mechanistic basis for the responses seen with entinostat and pembrolizumab in ENCORE-601, Dr. Ramalingam said.

“Now we acknowledge that this is a relatively small dataset, and therefore further studies are warranted using these biomarkers to further understand whether they can be used as predictive biomarkers for treatment,” he said, noting that one such clinical trial is currently in the discussion phase.

The ENCORE-601 findings are important given that “with the movement of checkpoint inhibitors to the front-line setting, there is now an unmet need in the second-line [setting] where patients have already received a checkpoint inhibitor and have developed disease progression,” he noted, adding that “while chemotherapy remains central to this group of patients, development of novel agents is an unmet need.”

Dr. Ramalingam disclosed ties to AbbVie, Advaxis, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Loxo, Merck, Nektar, Takeda, and Syndax.

sworcester@mdedge.com

SOURCE: Ramalingam S et al. AACR 2019, Abstract CT041.

ATLANTA – Combination entinostat and pembrolizumab showed promising activity in a phase 2 study of non–small cell lung cancer patients who progressed on or after anti-programmed death-ligand 1 (PD-L1) therapy, and new analyses have identified gene signatures associated with treatment response.

Gene set analysis in tumors from 43 of the patients – 4 responders and 39 nonresponders – who participated in the open-label ENCORE-601 study revealed that Myc gene signaling was enriched in responders vs. nonresponders, Suresh S. Ramalingam, MD, said at the annual meeting of the American Association for Cancer Research.

High Myc gene activity is known from previous studies to be associated with response to immune checkpoint inhibition, and this has been attributed to high PD-L1 expression, decrease in interferon signatures, and exclusion of lymphocytes, he noted.

“And we know from other publications that entinostat is known to decrease Myc activity,” he said. “Therefore, our putative hypothesis at this time – albeit on a small set of patients – is that for patients with baseline high Myc activity, when they have developed resistance to PD-1 or PD-L1 inhibition ... giving them entinostat drives down the Myc activity and results in a change in the tumor microenvironment to one where immune checkpoint inhibition could be rendered effective.”


Patients from ENCORE-601 also were evaluated by baseline circulating classical monocyte levels as prior findings showed improved overall survival and progression-free survival (PFS) in melanoma patients with higher vs. lower counts, Dr. Ramalingam explained.

The overall response rate (ORR) in those with baseline levels above the median (MHi, 11 patients) was 21.1% vs. 6.5% in those with levels below the median (MLo, 32 patients); median PFS was 4.7 vs. 2.7 months in the MHi and MLo groups, respectively, said Dr. Ramalingam of Winship Cancer Institute, Emory University, Atlanta.

ENCORE-601 included 76 subjects who received entinostat at a dose of 5 mg per week plus intravenous pembrolizumab at 200 mg every 3 weeks. The confirmed ORR with treatment in 72 efficacy-evaluable patients was 10%, with an additional 50% of patients having stable disease. The median duration of response was 8 months, and median PFS was 2.8 months.

Top-line results from the study, which was undertaken based in part on preclinical data showing synergy between the oral class 1-selective histone deacetylase inhibitor entinostat and anti-PD-1 inhibition, were presented at the 2018 World Conference on Lung Cancer, and the current findings represent secondary outcome measures involving analyses in pretreatment tumor samples from patients with sufficient RNA yield for analysis.


The data may provide a mechanistic basis for the responses seen with entinostat and pembrolizumab in ENCORE-601, Dr. Ramalingam said.

“Now we acknowledge that this is a relatively small dataset, and therefore further studies are warranted using these biomarkers to further understand whether they can be used as predictive biomarkers for treatment,” he said, noting that one such clinical trial is currently in the discussion phase.

The ENCORE-601 findings are important given that “with the movement of checkpoint inhibitors to the front-line setting, there is now an unmet need in the second-line [setting] where patients have already received a checkpoint inhibitor and have developed disease progression,” he noted, adding that “while chemotherapy remains central to this group of patients, development of novel agents is an unmet need.”

Dr. Ramalingam disclosed ties to AbbVie, Advaxis, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Loxo, Merck, Nektar, Takeda, and Syndax.

sworcester@mdedge.com

SOURCE: Ramalingam S et al. AACR 2019, Abstract CT041.

ATLANTA – Combination entinostat and pembrolizumab showed promising activity in a phase 2 study of non–small cell lung cancer patients who progressed on or after anti-programmed death-ligand 1 (PD-L1) therapy, and new analyses have identified gene signatures associated with treatment response.

Gene set analysis in tumors from 43 of the patients – 4 responders and 39 nonresponders – who participated in the open-label ENCORE-601 study revealed that Myc gene signaling was enriched in responders vs. nonresponders, Suresh S. Ramalingam, MD, said at the annual meeting of the American Association for Cancer Research.

High Myc gene activity is known from previous studies to be associated with response to immune checkpoint inhibition, and this has been attributed to high PD-L1 expression, decrease in interferon signatures, and exclusion of lymphocytes, he noted.

“And we know from other publications that entinostat is known to decrease Myc activity,” he said. “Therefore, our putative hypothesis at this time – albeit on a small set of patients – is that for patients with baseline high Myc activity, when they have developed resistance to PD-1 or PD-L1 inhibition ... giving them entinostat drives down the Myc activity and results in a change in the tumor microenvironment to one where immune checkpoint inhibition could be rendered effective.”


Patients from ENCORE-601 also were evaluated by baseline circulating classical monocyte levels as prior findings showed improved overall survival and progression-free survival (PFS) in melanoma patients with higher vs. lower counts, Dr. Ramalingam explained.

The overall response rate (ORR) in those with baseline levels above the median (MHi, 11 patients) was 21.1% vs. 6.5% in those with levels below the median (MLo, 32 patients); median PFS was 4.7 vs. 2.7 months in the MHi and MLo groups, respectively, said Dr. Ramalingam of Winship Cancer Institute, Emory University, Atlanta.

ENCORE-601 included 76 subjects who received entinostat at a dose of 5 mg per week plus intravenous pembrolizumab at 200 mg every 3 weeks. The confirmed ORR with treatment in 72 efficacy-evaluable patients was 10%, with an additional 50% of patients having stable disease. The median duration of response was 8 months, and median PFS was 2.8 months.

Top-line results from the study, which was undertaken based in part on preclinical data showing synergy between the oral class 1-selective histone deacetylase inhibitor entinostat and anti-PD-1 inhibition, were presented at the 2018 World Conference on Lung Cancer, and the current findings represent secondary outcome measures involving analyses in pretreatment tumor samples from patients with sufficient RNA yield for analysis.


The data may provide a mechanistic basis for the responses seen with entinostat and pembrolizumab in ENCORE-601, Dr. Ramalingam said.

“Now we acknowledge that this is a relatively small dataset, and therefore further studies are warranted using these biomarkers to further understand whether they can be used as predictive biomarkers for treatment,” he said, noting that one such clinical trial is currently in the discussion phase.

The ENCORE-601 findings are important given that “with the movement of checkpoint inhibitors to the front-line setting, there is now an unmet need in the second-line [setting] where patients have already received a checkpoint inhibitor and have developed disease progression,” he noted, adding that “while chemotherapy remains central to this group of patients, development of novel agents is an unmet need.”

Dr. Ramalingam disclosed ties to AbbVie, Advaxis, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Loxo, Merck, Nektar, Takeda, and Syndax.

sworcester@mdedge.com

SOURCE: Ramalingam S et al. AACR 2019, Abstract CT041.