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Cases of Drug-Associated Endocarditis Multiply
As the epidemic of opioid use has expanded, so has the incidence of drug-associated endocarditis. North Carolina, where CDC researchers analyzed discharge data from 128 hospitals, saw about a 12-fold jump in hospitalizations for endocarditis combined with drug dependence between 2010-2015.
The incidence of hospitalizations sharply increased, particularly beginning in 2013, from 0.2 cases per 100,000 persons per year in 2010 to 2.7 cases per 100,000 persons in 2015. The rise was fastest among adults aged 18 to 25 years.
About one-third of the patients also were infected with hepatitis C virus (HCV), a not unexpected finding since IV drug use is a recognized risk factor for both endocarditis and HCV infection.
The financial repercussions also are evident. Between 2010 and 2015, the median hospital charge for drug dependence-associated endocarditis hospitalization jumped from $1.1 million to $22.2 million—an 18-fold increase.
The findings suggest a need to focus on preventive interventions, the researchers say, such as fact-based drug education, syringe service programs, safe injection education, and treatment programs offering opioid agonist and antagonist therapies.
As the epidemic of opioid use has expanded, so has the incidence of drug-associated endocarditis. North Carolina, where CDC researchers analyzed discharge data from 128 hospitals, saw about a 12-fold jump in hospitalizations for endocarditis combined with drug dependence between 2010-2015.
The incidence of hospitalizations sharply increased, particularly beginning in 2013, from 0.2 cases per 100,000 persons per year in 2010 to 2.7 cases per 100,000 persons in 2015. The rise was fastest among adults aged 18 to 25 years.
About one-third of the patients also were infected with hepatitis C virus (HCV), a not unexpected finding since IV drug use is a recognized risk factor for both endocarditis and HCV infection.
The financial repercussions also are evident. Between 2010 and 2015, the median hospital charge for drug dependence-associated endocarditis hospitalization jumped from $1.1 million to $22.2 million—an 18-fold increase.
The findings suggest a need to focus on preventive interventions, the researchers say, such as fact-based drug education, syringe service programs, safe injection education, and treatment programs offering opioid agonist and antagonist therapies.
As the epidemic of opioid use has expanded, so has the incidence of drug-associated endocarditis. North Carolina, where CDC researchers analyzed discharge data from 128 hospitals, saw about a 12-fold jump in hospitalizations for endocarditis combined with drug dependence between 2010-2015.
The incidence of hospitalizations sharply increased, particularly beginning in 2013, from 0.2 cases per 100,000 persons per year in 2010 to 2.7 cases per 100,000 persons in 2015. The rise was fastest among adults aged 18 to 25 years.
About one-third of the patients also were infected with hepatitis C virus (HCV), a not unexpected finding since IV drug use is a recognized risk factor for both endocarditis and HCV infection.
The financial repercussions also are evident. Between 2010 and 2015, the median hospital charge for drug dependence-associated endocarditis hospitalization jumped from $1.1 million to $22.2 million—an 18-fold increase.
The findings suggest a need to focus on preventive interventions, the researchers say, such as fact-based drug education, syringe service programs, safe injection education, and treatment programs offering opioid agonist and antagonist therapies.
Nivolumab Linked to Nephritis in Melanoma
Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.
The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.
Related: Getting a Better Picture of Skin Cancer
The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.
The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.
A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.
The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.
Related: Immunotherapy in Melanoma
Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.
Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2
Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.
The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.
Related: Getting a Better Picture of Skin Cancer
The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.
The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.
A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.
The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.
Related: Immunotherapy in Melanoma
Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.
Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2
Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.
The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.
Related: Getting a Better Picture of Skin Cancer
The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.
The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.
A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.
The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.
Related: Immunotherapy in Melanoma
Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.
Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2
FDA approves first treatment for cGVHD
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia. 
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.
This makes ibrutinib the first FDA-approved therapy for cGVHD.
Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.
“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.
The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.
Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.
Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.
FDA grants drug orphan designation for PNH
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to RA101495 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
RA101495 is a synthetic, macrocyclic peptide being developed by Ra Pharmaceuticals.
The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
By binding to a region of C5 corresponding to C5b, RA101495 also disrupts the interaction between C5b and C6 and prevents assembly of the membrane attack complex.
In phase 1 studies, dosing of RA101495 was well tolerated in healthy volunteers and demonstrated sustained and near complete suppression of hemolysis and complement activity.
The phase 1 results were presented at the 21st Congress of the European Hematology Association in June 2016 (abstracts LB2249 and P632).
RA101495 is currently under investigation in a phase 2 trial of patients with PNH.
“There is an urgent need for new treatment options for patients suffering from PNH,” said Doug Treco, PhD, president and chief executive officer of Ra Pharmaceuticals.
“The current standard of care requires biweekly intravenous infusions, a dosing regimen that imposes a severe burden on patients, providers, and caregivers. We have designed RA101495 for once-daily, subcutaneous self-administration, an approach which has the potential to ease this burden, improve convenience, and provide much-needed dosing flexibility.”
“We are encouraged by our initial phase 2 data in PNH patients, which showed near-complete inhibition of hemolysis and a favorable safety and tolerability profile. We look forward to advancing our PNH program and providing additional data updates around year-end.”
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Hand pain and rash
The FP diagnosed psoriatic arthritis and psoriasis in this patient. The psoriatic arthritis had already caused swan neck deformities of multiple fingers, consistent with the mutilans subtype of psoriatic arthritis. The FP was aware that this patient needed to see a dermatologist and/or rheumatologist due to the severity of the arthritis.
Patients like this need systemic therapy with methotrexate, apremilast, or an anti-tumor necrosis factor alpha-inhibitor on an ongoing basis to both treat the arthritis and attempt to prevent further joint destruction. This will also treat the extensive plaque psoriasis that may accompany psoriatic arthritis. Most patients with psoriatic arthritis also have nail involvement (as did this patient), and it may respond to systemic treatment, as well.
Since systemic treatment is frequently outside the FP’s scope of practice, referral to a specialist is essential. The FP can, however, start topical therapy for the plaque psoriasis. This can be initiated with mid- to high-potency topical steroids.
It may be tempting to give a patient like this oral prednisone or an intramuscular steroid, but such therapy should be avoided because it can result in rebound pustular psoriasis. (These treatments do not work well enough to take the risk.)
In this case, the FP prescribed a 60-g tube of 0.05% clobetasol ointment to be applied to the worst areas, along with a 1-lb tub (454 g) of 0.1% triamcinolone to be applied to the other plaques. The patient was glad to receive treatment for his psoriasis and looked forward to seeing a specialist for treatment of his arthritis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP diagnosed psoriatic arthritis and psoriasis in this patient. The psoriatic arthritis had already caused swan neck deformities of multiple fingers, consistent with the mutilans subtype of psoriatic arthritis. The FP was aware that this patient needed to see a dermatologist and/or rheumatologist due to the severity of the arthritis.
Patients like this need systemic therapy with methotrexate, apremilast, or an anti-tumor necrosis factor alpha-inhibitor on an ongoing basis to both treat the arthritis and attempt to prevent further joint destruction. This will also treat the extensive plaque psoriasis that may accompany psoriatic arthritis. Most patients with psoriatic arthritis also have nail involvement (as did this patient), and it may respond to systemic treatment, as well.
Since systemic treatment is frequently outside the FP’s scope of practice, referral to a specialist is essential. The FP can, however, start topical therapy for the plaque psoriasis. This can be initiated with mid- to high-potency topical steroids.
It may be tempting to give a patient like this oral prednisone or an intramuscular steroid, but such therapy should be avoided because it can result in rebound pustular psoriasis. (These treatments do not work well enough to take the risk.)
In this case, the FP prescribed a 60-g tube of 0.05% clobetasol ointment to be applied to the worst areas, along with a 1-lb tub (454 g) of 0.1% triamcinolone to be applied to the other plaques. The patient was glad to receive treatment for his psoriasis and looked forward to seeing a specialist for treatment of his arthritis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP diagnosed psoriatic arthritis and psoriasis in this patient. The psoriatic arthritis had already caused swan neck deformities of multiple fingers, consistent with the mutilans subtype of psoriatic arthritis. The FP was aware that this patient needed to see a dermatologist and/or rheumatologist due to the severity of the arthritis.
Patients like this need systemic therapy with methotrexate, apremilast, or an anti-tumor necrosis factor alpha-inhibitor on an ongoing basis to both treat the arthritis and attempt to prevent further joint destruction. This will also treat the extensive plaque psoriasis that may accompany psoriatic arthritis. Most patients with psoriatic arthritis also have nail involvement (as did this patient), and it may respond to systemic treatment, as well.
Since systemic treatment is frequently outside the FP’s scope of practice, referral to a specialist is essential. The FP can, however, start topical therapy for the plaque psoriasis. This can be initiated with mid- to high-potency topical steroids.
It may be tempting to give a patient like this oral prednisone or an intramuscular steroid, but such therapy should be avoided because it can result in rebound pustular psoriasis. (These treatments do not work well enough to take the risk.)
In this case, the FP prescribed a 60-g tube of 0.05% clobetasol ointment to be applied to the worst areas, along with a 1-lb tub (454 g) of 0.1% triamcinolone to be applied to the other plaques. The patient was glad to receive treatment for his psoriasis and looked forward to seeing a specialist for treatment of his arthritis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Psoriasis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 878-895.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
Slow and Steady: A Worrisome Pace
ANSWER
The false statement is that most melanomas are raised (choice “a”), since most melanomas are essentially macular (flat).
DISCUSSION
Misconceptions about melanomas often delay diagnosis, costing lives. In truth, the majority of melanomas are difficult, if not impossible, to feel on palpation. This is because they arise in the skin, rather than on it.
Malignant melanomas are cancers of melanocytes (the cells that line the basal cell layer). Overexposure to UV sources damages the nuclei of these cells, compromising their ability to repair the damage. This can lead to focally unregulated cell growth.
Initially, this uncontrolled cell replication spreads horizontally. Over time, though, it can grow vertically and penetrate deep enough to invade the vasculature (roughly 1 mm deep), and spread to the liver, lung, or brain. This is why ascertaining the depth of a melanoma is critical for predicting prognosis and determining the extent of additional surgery and search for evidence of metastatic disease.
Melanomas do not typically itch or bleed until they are advanced (if at all). And most arise de novo (as new lesions, rather than pre-existing). So, contrary to popular belief, moles rarely turn into melanomas.
It is also true that approximately 80% of all melanomas arise on skin normally covered by clothing, despite the role of sunlight in the development of melanoma. For reasons not totally understood, the combination of fair, su
ANSWER
The false statement is that most melanomas are raised (choice “a”), since most melanomas are essentially macular (flat).
DISCUSSION
Misconceptions about melanomas often delay diagnosis, costing lives. In truth, the majority of melanomas are difficult, if not impossible, to feel on palpation. This is because they arise in the skin, rather than on it.
Malignant melanomas are cancers of melanocytes (the cells that line the basal cell layer). Overexposure to UV sources damages the nuclei of these cells, compromising their ability to repair the damage. This can lead to focally unregulated cell growth.
Initially, this uncontrolled cell replication spreads horizontally. Over time, though, it can grow vertically and penetrate deep enough to invade the vasculature (roughly 1 mm deep), and spread to the liver, lung, or brain. This is why ascertaining the depth of a melanoma is critical for predicting prognosis and determining the extent of additional surgery and search for evidence of metastatic disease.
Melanomas do not typically itch or bleed until they are advanced (if at all). And most arise de novo (as new lesions, rather than pre-existing). So, contrary to popular belief, moles rarely turn into melanomas.
It is also true that approximately 80% of all melanomas arise on skin normally covered by clothing, despite the role of sunlight in the development of melanoma. For reasons not totally understood, the combination of fair, su
ANSWER
The false statement is that most melanomas are raised (choice “a”), since most melanomas are essentially macular (flat).
DISCUSSION
Misconceptions about melanomas often delay diagnosis, costing lives. In truth, the majority of melanomas are difficult, if not impossible, to feel on palpation. This is because they arise in the skin, rather than on it.
Malignant melanomas are cancers of melanocytes (the cells that line the basal cell layer). Overexposure to UV sources damages the nuclei of these cells, compromising their ability to repair the damage. This can lead to focally unregulated cell growth.
Initially, this uncontrolled cell replication spreads horizontally. Over time, though, it can grow vertically and penetrate deep enough to invade the vasculature (roughly 1 mm deep), and spread to the liver, lung, or brain. This is why ascertaining the depth of a melanoma is critical for predicting prognosis and determining the extent of additional surgery and search for evidence of metastatic disease.
Melanomas do not typically itch or bleed until they are advanced (if at all). And most arise de novo (as new lesions, rather than pre-existing). So, contrary to popular belief, moles rarely turn into melanomas.
It is also true that approximately 80% of all melanomas arise on skin normally covered by clothing, despite the role of sunlight in the development of melanoma. For reasons not totally understood, the combination of fair, su
For more than two years, a 43-year-old man has had an asymptomatic lesion on his right deltoid area. His primary care provider has repeatedly assured him of its benignancy “because it is flat.” But its slow, steady, horizontal growth concerns the patient, who is otherwise healthy.
He does admit to a significant history of sun exposure, explaining that he burns easily but acquires a tan by summer’s end each year. Several members of his immediate family have had skin cancers removed.
Examination reveals a round, dark macule, measuring 1.1 cm, on the right lateral deltoid area. The lesion has poorly defined borders and a variety of colors—mostly black and brown, with flecks of red and pink. There is no palpable component, and no nodes can be detected in the area.
The rest of his type II skin has abundant evidence of UV overexposure, including solar lentigines and weathering, especially around the neck.
The lesion is anesthetized, removed by deep shave technique, and submitted to pathology. The report shows a superficial, spreading melanoma with a Breslow depth of 0.75 mm. Malignant cells extend to the dermoepidermal junction (Clark level II). Only a few mitotic cells can be seen, with no intravascular invasion or signs of ulceration.
Syncope Guidelines
Title: 2017 ACC/AHA/HRS guidelines for patients with syncope
Clinical Question: What are the key points from the 2017 ACC/AHA/HRS guidelines for the evaluation and management of adult patients with syncope?
Background: Syncope is a common condition for which patients present to a hospital setting. Updated guidance and recommendations on the evaluation and management of syncope are provided.
Study Design: Evidence-based guidelines.
Setting: Panel of experts.
Synopsis: A detailed history and physical should be performed. A 12-lead ECG should be obtained. Short- and long-term morbidity and mortality risk of syncope should be assessed. Inpatient evaluation and treatment is recommended for patients presenting with syncope and who have serious medical condition relevant to the cause of syncope. Lab tests are not useful. Routine cardiac imaging is not useful unless a cardiac etiology of syncope is suspected. Carotid artery imaging is not useful in the absence of focal neurologic findings. Continuous telemetry is indicated for inpatients suspected of syncope due to a cardiac etiology.
The most common cause of syncope is vasovagal. Medication therapy has modest effect, and patient education is recommended. Dual chamber pacing may be reasonable in select patients over the age of 40 with recurrent vasovagal syncope and prolonged spontaneous pauses. If orthostatic hypotension is suspected as the cause of syncope due to dehydration, then fluid resuscitation is recommended. Removing medications causing hypotension may be appropriate for select patients with syncope.
Cardiac syncope requires expert directed care and may include life-style changes, medication therapy and/or procedural intervention.
Bottom Line: The 2017 syncope guidelines provide updated and concise recommendations on the management of syncope.
Citation: Shen W-K, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive summary. Journal of the American College of Cardiology. 2017; doi: 10.1016/ j.jacc.2017.03.002.
Dr. Burns is assistant professor in the division of hospital medicine at the University of New Mexico.
Title: 2017 ACC/AHA/HRS guidelines for patients with syncope
Clinical Question: What are the key points from the 2017 ACC/AHA/HRS guidelines for the evaluation and management of adult patients with syncope?
Background: Syncope is a common condition for which patients present to a hospital setting. Updated guidance and recommendations on the evaluation and management of syncope are provided.
Study Design: Evidence-based guidelines.
Setting: Panel of experts.
Synopsis: A detailed history and physical should be performed. A 12-lead ECG should be obtained. Short- and long-term morbidity and mortality risk of syncope should be assessed. Inpatient evaluation and treatment is recommended for patients presenting with syncope and who have serious medical condition relevant to the cause of syncope. Lab tests are not useful. Routine cardiac imaging is not useful unless a cardiac etiology of syncope is suspected. Carotid artery imaging is not useful in the absence of focal neurologic findings. Continuous telemetry is indicated for inpatients suspected of syncope due to a cardiac etiology.
The most common cause of syncope is vasovagal. Medication therapy has modest effect, and patient education is recommended. Dual chamber pacing may be reasonable in select patients over the age of 40 with recurrent vasovagal syncope and prolonged spontaneous pauses. If orthostatic hypotension is suspected as the cause of syncope due to dehydration, then fluid resuscitation is recommended. Removing medications causing hypotension may be appropriate for select patients with syncope.
Cardiac syncope requires expert directed care and may include life-style changes, medication therapy and/or procedural intervention.
Bottom Line: The 2017 syncope guidelines provide updated and concise recommendations on the management of syncope.
Citation: Shen W-K, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive summary. Journal of the American College of Cardiology. 2017; doi: 10.1016/ j.jacc.2017.03.002.
Dr. Burns is assistant professor in the division of hospital medicine at the University of New Mexico.
Title: 2017 ACC/AHA/HRS guidelines for patients with syncope
Clinical Question: What are the key points from the 2017 ACC/AHA/HRS guidelines for the evaluation and management of adult patients with syncope?
Background: Syncope is a common condition for which patients present to a hospital setting. Updated guidance and recommendations on the evaluation and management of syncope are provided.
Study Design: Evidence-based guidelines.
Setting: Panel of experts.
Synopsis: A detailed history and physical should be performed. A 12-lead ECG should be obtained. Short- and long-term morbidity and mortality risk of syncope should be assessed. Inpatient evaluation and treatment is recommended for patients presenting with syncope and who have serious medical condition relevant to the cause of syncope. Lab tests are not useful. Routine cardiac imaging is not useful unless a cardiac etiology of syncope is suspected. Carotid artery imaging is not useful in the absence of focal neurologic findings. Continuous telemetry is indicated for inpatients suspected of syncope due to a cardiac etiology.
The most common cause of syncope is vasovagal. Medication therapy has modest effect, and patient education is recommended. Dual chamber pacing may be reasonable in select patients over the age of 40 with recurrent vasovagal syncope and prolonged spontaneous pauses. If orthostatic hypotension is suspected as the cause of syncope due to dehydration, then fluid resuscitation is recommended. Removing medications causing hypotension may be appropriate for select patients with syncope.
Cardiac syncope requires expert directed care and may include life-style changes, medication therapy and/or procedural intervention.
Bottom Line: The 2017 syncope guidelines provide updated and concise recommendations on the management of syncope.
Citation: Shen W-K, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive summary. Journal of the American College of Cardiology. 2017; doi: 10.1016/ j.jacc.2017.03.002.
Dr. Burns is assistant professor in the division of hospital medicine at the University of New Mexico.
FDA committee rejects sirukumab approval on safety concerns
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
Citing safety concerns, the Food and Drug Administration’s Arthritis Advisory Committee voted overwhelmingly against recommending FDA approval of the interleukin-6 inhibitor sirukumab for refractory rheumatoid arthritis.
Janssen Biotech submitted a biologics license application (BLA) for the monoclonal antibody, seeking an indication for adults with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response or intolerance to one or more prior disease-modifying antirheumatic drugs, but despite agreeing unanimously that the data presented by the applicant provided substantial evidence of efficacy for this indication, the committee voted 12-1 against approval at an Aug. 2 meeting.
“I’m not sure whether the safety signal is of concern or not. I don’t think there’s enough data here to know that. It’s concerning, and it may be just noise, but it may also be real and I’m not willing to ... be supportive of the notion that it’s safe enough to take its place along with other biologicals,” said temporary voting member David T. Felson, MD, professor of medicine and public health at Boston University.
Similarly, temporary voting member Erica Brittain, PhD, said the mortality concerns swayed her vote.
“It was a very close call for me. I do think there’s a real argument to be made about bias in the analysis that shows some possibility of a difference. On the other hand, I just couldn’t get past the uncertainty, and when we’re talking about mortality it’s hard to dismiss that,” said Dr. Brittain, a mathematical statistician and deputy chief of the Biostatistics Research Branch at the National Institute of Allergy and Infectious Diseases.
Michael H. Weisman, MD, also a temporary voting member and chair of rheumatology at Cedars-Sinai Medical Center in Los Angeles, said that if the indication had been narrowed – perhaps to those who showed a biologic response – he would have voted “yes.”
Temporary voting member James Katz, MD, was the only committee member to vote in favor of approval.
“I actually voted yes because this drug doesn’t scare me any more than all the other drugs I use. I’m very scared by all the biological agents, and this is no different,” said Dr. Katz, director of the Rheumatology Fellowship and Training Branch at the National Institute of Arthritis and Musculoskeletal Diseases.
Sirukumab differs from two other approved monoclonal antibodies that target the IL-6 pathway for the treatment of patients with RA – tocilizumab (Actemra) and sarilumab (Kevzara) – in that it targets IL-6, while the others target the IL-6 receptor. This slight difference could make a difference for some highly refractory patients who had failed to respond to prior treatments, according to applicant presentations at the meeting.
The efficacy and safety of the agent were assessed in a phase 2 dose-ranging study, as well in three pivotal phase 3 studies. Two of the phase 3 studies compared 100 mg twice weekly and 50 mg four times weekly doses of subcutaneous sirukumab to placebo – which were shown to have similar efficacy for reducing the signs and symptoms of RA – and a third compared those two doses against adalimumab (Humira) and showed that it was not superior to adalimumab for efficacy.
One phase 3 placebo-controlled study involving 878 refractory patients was published in February in The Lancet and showed that sirukumab was associated with rapid and sustained improvements in RA signs and symptoms, physical function, and health status, as well as improvement in physical and mental well-being.
However, a safety signal – a trend of increased overall mortality with sirukumab vs. placebo – emerged from the studies. The mortality was mainly associated with major adverse cardiovascular events, infection, and malignancy.
Three speakers, including RA patients or patient representatives, participated in the open public hearing portion of the committee meeting, and all spoke in favor of approval of sirukumab, but ultimately the committee agreed that the limited benefits of the agent – given that it does not involve an entirely new mechanism of action – did not outweigh the unknowns regarding safety.
Committee chairperson Daniel H. Solomon, MD, professor of medicine at Harvard Medical School and chief of the section of clinical sciences at Brigham and Women’s Hospital, both in Boston, said longer-term outcomes data with a clear comparator are needed.
The FDA will now consider the committee’s recommendations in making its final determination regarding the BLA.
All voting advisory committee members were screened and cleared with respect to potential conflicts of interest.
Abilify Maintena OK’d by FDA for adults with bipolar I disorder
The Food and Drug Administration has approved a monthly injectable formulation of aripiprazole, (Abilify Maintena) , for a maintenance monotherapy treatment of bipolar I disorder for adults, Otsuka and Lundbeck have announced.
Patients treated with the injectable formulation of the atypical antipsychotic must continue to take a daily oral antipsychotic for the first 14 days. After that, however, the long-acting injectable (LAI) – which must be administered by a health care professional – can replace the daily medication.
Joseph R. Calabrese, MD, director of the mood disorders program at University Hospitals Cleveland Medical Center, said in the July 28 announcement that the LAI is a new treatment option for bipolar I patients “who have established tolerability with oral aripiprazole.”
The drug label includes a warning that elderly patients with dementia-related psychosis who are treated with antipsychotics are at a higher mortality risk. Adverse reactions that have been associated with treatment with aripiprazole include weight gain, akathisia, injection site pain, sedation, and certain compulsive behaviors.
Created by Otsuka, and marketed by Otsuka and Lundbeck, the LAI was approved in the United States for treating adults with schizophrenia in 2013.
The Food and Drug Administration has approved a monthly injectable formulation of aripiprazole, (Abilify Maintena) , for a maintenance monotherapy treatment of bipolar I disorder for adults, Otsuka and Lundbeck have announced.
Patients treated with the injectable formulation of the atypical antipsychotic must continue to take a daily oral antipsychotic for the first 14 days. After that, however, the long-acting injectable (LAI) – which must be administered by a health care professional – can replace the daily medication.
Joseph R. Calabrese, MD, director of the mood disorders program at University Hospitals Cleveland Medical Center, said in the July 28 announcement that the LAI is a new treatment option for bipolar I patients “who have established tolerability with oral aripiprazole.”
The drug label includes a warning that elderly patients with dementia-related psychosis who are treated with antipsychotics are at a higher mortality risk. Adverse reactions that have been associated with treatment with aripiprazole include weight gain, akathisia, injection site pain, sedation, and certain compulsive behaviors.
Created by Otsuka, and marketed by Otsuka and Lundbeck, the LAI was approved in the United States for treating adults with schizophrenia in 2013.
The Food and Drug Administration has approved a monthly injectable formulation of aripiprazole, (Abilify Maintena) , for a maintenance monotherapy treatment of bipolar I disorder for adults, Otsuka and Lundbeck have announced.
Patients treated with the injectable formulation of the atypical antipsychotic must continue to take a daily oral antipsychotic for the first 14 days. After that, however, the long-acting injectable (LAI) – which must be administered by a health care professional – can replace the daily medication.
Joseph R. Calabrese, MD, director of the mood disorders program at University Hospitals Cleveland Medical Center, said in the July 28 announcement that the LAI is a new treatment option for bipolar I patients “who have established tolerability with oral aripiprazole.”
The drug label includes a warning that elderly patients with dementia-related psychosis who are treated with antipsychotics are at a higher mortality risk. Adverse reactions that have been associated with treatment with aripiprazole include weight gain, akathisia, injection site pain, sedation, and certain compulsive behaviors.
Created by Otsuka, and marketed by Otsuka and Lundbeck, the LAI was approved in the United States for treating adults with schizophrenia in 2013.
Forced commitments still low under California’s AOT law
Critics have feared that California’s “Laura’s Law,” designed to prevent violence by making it easier for officials to force outpatient care upon people with mental illness who have resisted treatment, would violate the civil rights of Golden State residents.
But early statistics gathered by a Northern California psychiatrist suggest that few people have been forced involuntarily into outpatient care in large counties that have adopted the tougher approach in recent years. Instead, Californians targeted by the law appear to be choosing – under pressure – the alternative of accepting outpatient treatment.
California enacted Laura’s Law in 2003 after the death of a 19-year-old woman named Laura Wilcox at a mental health clinic in Northern California. Ms. Wilcox, who worked at the clinic, and two others were shot to death by a patient whose family had failed to persuade officials to force him to get treatment.
As California’s version of assisted outpatient treatment, or AOT, Laura’s Law, allows courts to order people into outpatient treatment in cases that meet certain criteria. Among other things, the person must have a mental illness, be considered “unlikely to survive safely in the community without supervision,” and have a “history of lack of compliance with treatment.” The law “also obligates any county that implements and accepts the law to provide excellent and comprehensive community-based services, not only for court-ordered patients but anybody who wants care,” Dr. Nelson said in an interview after his presentation.
As a state law, the measure must be adopted on a county-by-county basis. Tiny and remote Nevada County, where the shootings occurred, adopted the policy first when it was forced to do so by a lawsuit, Dr. Nelson said. But other counties were slow to sign on.
“Unlike Kendra’s Law, which passed earlier in New York, and both mandated and funded assisted outpatient treatment for all counties, Laura’s Law was completely unfunded. It was left to the discretion of each county to decide for itself whether or not to implement,” said Dr. Nelson, of Marin County, just north of San Francisco, who has served on the councils of the Northern California Psychiatric Society and California Psychiatric Association.
But things changed in 2013, when the state allowed money from a special tax on wealthy residents to be used for AOT programs, Dr. Nelson said. Counties began implementing Laura’s Law in 2014, and the number has now reached 17, representing about two-thirds of the state’s population, he said.
Dr. Nelson gathered statistics from several of California’s 58 counties. He found that over a period of 5 months of implementation, 59 people were referred to the AOT program, and 12 voluntarily accepted outpatient therapy in San Francisco County, which encompasses the city of San Francisco only and has 864,000 residents.
Over a period of 5 months in San Diego County, which has 3.3 million residents, there were 376 referrals, including those to a program that uses home visits to urge people to accept outpatient care. Twenty people accepted voluntary outpatient treatment. No court-ordered treatment was required for anyone in either San Diego or San Francisco counties.
Over a period of 12 months in Orange County, with 3.2 million residents, there were 389 referrals, and 126 people voluntarily accepted AOT. Only three were ordered into treatment by courts. Over 6 months in Placer County, with just 375,000 residents, eight patients voluntarily accepted AOT, and one was ordered into treatment by a court but refused it.
(The Orange County Register reports that refusal to abide by court-ordered outpatient treatment results in no civil or criminal penalties.)
Los Angeles County, by far the most populous in the state with 10.1 million residents, reported 805 AOT referrals, 30 involuntary commitments to outpatient care, and 239 voluntary agreements to outpatient care. The numbers are from 2016 to 2017, but Dr. Nelson did not have details about the exact period covered.
Dr. Nelson also looked at 7 years of statistics from Nevada County, which was forced into adopting an AOT program by a lawsuit. The county, which has fewer than 100,000 residents, reported 67 referrals to the AOT program and 30 cases of court-ordered treatment.
A report estimates that over the first 30 months of the program, Nevada County saved $1.80 for every $1 spent on its AOT program by preventing acute psychiatric hospitalizations and imprisonment.
The low numbers of forced commitments to outpatient care across the state make sense, Dr. Nelson said, since the law wasn’t intended to “force a bunch of folks with typically high recidivism with mental illness into involuntary treatment.”
Instead, he said, the law has promoted a so-called black robe effect – essentially, a form of intimidation by judge.
Dr. Nelson said he has tracked the debate over forced outpatient care for years and has mixed feelings about the law.
There’s value to coaxing people with mental illness into care when they are unable to recognize their illness, he said. “But there are way too many gaps and holes for people to fall into,” he said. “They have the potential to be mistreated, poorly treated, poorly diagnosed.”
While Laura’s Law requires counties to offer comprehensive outpatient mental health care, “it’s really difficult to know whether the programs are meeting all of the conditions of the law,” Dr. Nelson said.
Still, he said, Laura’s Law is forcing counties to discuss how to care for people with mental illness who are targeted by the legislation, he said. “They are beginning to have a lively conversation about how we are going to reach out to these people and help them, even to just avoid the implementation of Laura’s Law.”
Dr. Nelson has no relevant disclosures.
Critics have feared that California’s “Laura’s Law,” designed to prevent violence by making it easier for officials to force outpatient care upon people with mental illness who have resisted treatment, would violate the civil rights of Golden State residents.
But early statistics gathered by a Northern California psychiatrist suggest that few people have been forced involuntarily into outpatient care in large counties that have adopted the tougher approach in recent years. Instead, Californians targeted by the law appear to be choosing – under pressure – the alternative of accepting outpatient treatment.
California enacted Laura’s Law in 2003 after the death of a 19-year-old woman named Laura Wilcox at a mental health clinic in Northern California. Ms. Wilcox, who worked at the clinic, and two others were shot to death by a patient whose family had failed to persuade officials to force him to get treatment.
As California’s version of assisted outpatient treatment, or AOT, Laura’s Law, allows courts to order people into outpatient treatment in cases that meet certain criteria. Among other things, the person must have a mental illness, be considered “unlikely to survive safely in the community without supervision,” and have a “history of lack of compliance with treatment.” The law “also obligates any county that implements and accepts the law to provide excellent and comprehensive community-based services, not only for court-ordered patients but anybody who wants care,” Dr. Nelson said in an interview after his presentation.
As a state law, the measure must be adopted on a county-by-county basis. Tiny and remote Nevada County, where the shootings occurred, adopted the policy first when it was forced to do so by a lawsuit, Dr. Nelson said. But other counties were slow to sign on.
“Unlike Kendra’s Law, which passed earlier in New York, and both mandated and funded assisted outpatient treatment for all counties, Laura’s Law was completely unfunded. It was left to the discretion of each county to decide for itself whether or not to implement,” said Dr. Nelson, of Marin County, just north of San Francisco, who has served on the councils of the Northern California Psychiatric Society and California Psychiatric Association.
But things changed in 2013, when the state allowed money from a special tax on wealthy residents to be used for AOT programs, Dr. Nelson said. Counties began implementing Laura’s Law in 2014, and the number has now reached 17, representing about two-thirds of the state’s population, he said.
Dr. Nelson gathered statistics from several of California’s 58 counties. He found that over a period of 5 months of implementation, 59 people were referred to the AOT program, and 12 voluntarily accepted outpatient therapy in San Francisco County, which encompasses the city of San Francisco only and has 864,000 residents.
Over a period of 5 months in San Diego County, which has 3.3 million residents, there were 376 referrals, including those to a program that uses home visits to urge people to accept outpatient care. Twenty people accepted voluntary outpatient treatment. No court-ordered treatment was required for anyone in either San Diego or San Francisco counties.
Over a period of 12 months in Orange County, with 3.2 million residents, there were 389 referrals, and 126 people voluntarily accepted AOT. Only three were ordered into treatment by courts. Over 6 months in Placer County, with just 375,000 residents, eight patients voluntarily accepted AOT, and one was ordered into treatment by a court but refused it.
(The Orange County Register reports that refusal to abide by court-ordered outpatient treatment results in no civil or criminal penalties.)
Los Angeles County, by far the most populous in the state with 10.1 million residents, reported 805 AOT referrals, 30 involuntary commitments to outpatient care, and 239 voluntary agreements to outpatient care. The numbers are from 2016 to 2017, but Dr. Nelson did not have details about the exact period covered.
Dr. Nelson also looked at 7 years of statistics from Nevada County, which was forced into adopting an AOT program by a lawsuit. The county, which has fewer than 100,000 residents, reported 67 referrals to the AOT program and 30 cases of court-ordered treatment.
A report estimates that over the first 30 months of the program, Nevada County saved $1.80 for every $1 spent on its AOT program by preventing acute psychiatric hospitalizations and imprisonment.
The low numbers of forced commitments to outpatient care across the state make sense, Dr. Nelson said, since the law wasn’t intended to “force a bunch of folks with typically high recidivism with mental illness into involuntary treatment.”
Instead, he said, the law has promoted a so-called black robe effect – essentially, a form of intimidation by judge.
Dr. Nelson said he has tracked the debate over forced outpatient care for years and has mixed feelings about the law.
There’s value to coaxing people with mental illness into care when they are unable to recognize their illness, he said. “But there are way too many gaps and holes for people to fall into,” he said. “They have the potential to be mistreated, poorly treated, poorly diagnosed.”
While Laura’s Law requires counties to offer comprehensive outpatient mental health care, “it’s really difficult to know whether the programs are meeting all of the conditions of the law,” Dr. Nelson said.
Still, he said, Laura’s Law is forcing counties to discuss how to care for people with mental illness who are targeted by the legislation, he said. “They are beginning to have a lively conversation about how we are going to reach out to these people and help them, even to just avoid the implementation of Laura’s Law.”
Dr. Nelson has no relevant disclosures.
Critics have feared that California’s “Laura’s Law,” designed to prevent violence by making it easier for officials to force outpatient care upon people with mental illness who have resisted treatment, would violate the civil rights of Golden State residents.
But early statistics gathered by a Northern California psychiatrist suggest that few people have been forced involuntarily into outpatient care in large counties that have adopted the tougher approach in recent years. Instead, Californians targeted by the law appear to be choosing – under pressure – the alternative of accepting outpatient treatment.
California enacted Laura’s Law in 2003 after the death of a 19-year-old woman named Laura Wilcox at a mental health clinic in Northern California. Ms. Wilcox, who worked at the clinic, and two others were shot to death by a patient whose family had failed to persuade officials to force him to get treatment.
As California’s version of assisted outpatient treatment, or AOT, Laura’s Law, allows courts to order people into outpatient treatment in cases that meet certain criteria. Among other things, the person must have a mental illness, be considered “unlikely to survive safely in the community without supervision,” and have a “history of lack of compliance with treatment.” The law “also obligates any county that implements and accepts the law to provide excellent and comprehensive community-based services, not only for court-ordered patients but anybody who wants care,” Dr. Nelson said in an interview after his presentation.
As a state law, the measure must be adopted on a county-by-county basis. Tiny and remote Nevada County, where the shootings occurred, adopted the policy first when it was forced to do so by a lawsuit, Dr. Nelson said. But other counties were slow to sign on.
“Unlike Kendra’s Law, which passed earlier in New York, and both mandated and funded assisted outpatient treatment for all counties, Laura’s Law was completely unfunded. It was left to the discretion of each county to decide for itself whether or not to implement,” said Dr. Nelson, of Marin County, just north of San Francisco, who has served on the councils of the Northern California Psychiatric Society and California Psychiatric Association.
But things changed in 2013, when the state allowed money from a special tax on wealthy residents to be used for AOT programs, Dr. Nelson said. Counties began implementing Laura’s Law in 2014, and the number has now reached 17, representing about two-thirds of the state’s population, he said.
Dr. Nelson gathered statistics from several of California’s 58 counties. He found that over a period of 5 months of implementation, 59 people were referred to the AOT program, and 12 voluntarily accepted outpatient therapy in San Francisco County, which encompasses the city of San Francisco only and has 864,000 residents.
Over a period of 5 months in San Diego County, which has 3.3 million residents, there were 376 referrals, including those to a program that uses home visits to urge people to accept outpatient care. Twenty people accepted voluntary outpatient treatment. No court-ordered treatment was required for anyone in either San Diego or San Francisco counties.
Over a period of 12 months in Orange County, with 3.2 million residents, there were 389 referrals, and 126 people voluntarily accepted AOT. Only three were ordered into treatment by courts. Over 6 months in Placer County, with just 375,000 residents, eight patients voluntarily accepted AOT, and one was ordered into treatment by a court but refused it.
(The Orange County Register reports that refusal to abide by court-ordered outpatient treatment results in no civil or criminal penalties.)
Los Angeles County, by far the most populous in the state with 10.1 million residents, reported 805 AOT referrals, 30 involuntary commitments to outpatient care, and 239 voluntary agreements to outpatient care. The numbers are from 2016 to 2017, but Dr. Nelson did not have details about the exact period covered.
Dr. Nelson also looked at 7 years of statistics from Nevada County, which was forced into adopting an AOT program by a lawsuit. The county, which has fewer than 100,000 residents, reported 67 referrals to the AOT program and 30 cases of court-ordered treatment.
A report estimates that over the first 30 months of the program, Nevada County saved $1.80 for every $1 spent on its AOT program by preventing acute psychiatric hospitalizations and imprisonment.
The low numbers of forced commitments to outpatient care across the state make sense, Dr. Nelson said, since the law wasn’t intended to “force a bunch of folks with typically high recidivism with mental illness into involuntary treatment.”
Instead, he said, the law has promoted a so-called black robe effect – essentially, a form of intimidation by judge.
Dr. Nelson said he has tracked the debate over forced outpatient care for years and has mixed feelings about the law.
There’s value to coaxing people with mental illness into care when they are unable to recognize their illness, he said. “But there are way too many gaps and holes for people to fall into,” he said. “They have the potential to be mistreated, poorly treated, poorly diagnosed.”
While Laura’s Law requires counties to offer comprehensive outpatient mental health care, “it’s really difficult to know whether the programs are meeting all of the conditions of the law,” Dr. Nelson said.
Still, he said, Laura’s Law is forcing counties to discuss how to care for people with mental illness who are targeted by the legislation, he said. “They are beginning to have a lively conversation about how we are going to reach out to these people and help them, even to just avoid the implementation of Laura’s Law.”
Dr. Nelson has no relevant disclosures.
EXPERT ANALYSIS FROM APA