The FDA has given the nod to a new indication for the NSS-2 Bridge, an electronic device that was cleared for use in acupuncture in 2014. Now it is approved for reducing the symptoms of opioid withdrawal.

The NSS-2 Bridge is a small electrical nerve stimulator placed behind a patient’s ear. A battery-powered chip sends electrical pulses to stimulate branches of certain cranial nerves. Patients can use the device for up to 5 days during the acute phase of physical withdrawal.

The approval was based on results from a clinical study of 73 patients in withdrawal, evaluating their symptoms on the Clinical Opiate Withdrawal Scale (COWS), which measures signs and symptoms such as resting pulse rate, sweating, pupil size, gastrointestinal issues, bone and joint aches, tremors, and anxiety. The COWS scores range from 0 to > 36. The higher the score, the more severe the symptoms.

Before patients used the device, their average COWS score was 20.1. Within 30 minutes, all patient scores dropped by at least 31%. Nearly all (88%) the patients transitioned to medication-assisted therapy after 5 days of using the device.

The FDA has given the nod to a new indication for the NSS-2 Bridge, an electronic device that was cleared for use in acupuncture in 2014. Now it is approved for reducing the symptoms of opioid withdrawal.

The NSS-2 Bridge is a small electrical nerve stimulator placed behind a patient’s ear. A battery-powered chip sends electrical pulses to stimulate branches of certain cranial nerves. Patients can use the device for up to 5 days during the acute phase of physical withdrawal.

The approval was based on results from a clinical study of 73 patients in withdrawal, evaluating their symptoms on the Clinical Opiate Withdrawal Scale (COWS), which measures signs and symptoms such as resting pulse rate, sweating, pupil size, gastrointestinal issues, bone and joint aches, tremors, and anxiety. The COWS scores range from 0 to > 36. The higher the score, the more severe the symptoms.

Before patients used the device, their average COWS score was 20.1. Within 30 minutes, all patient scores dropped by at least 31%. Nearly all (88%) the patients transitioned to medication-assisted therapy after 5 days of using the device.

The FDA has given the nod to a new indication for the NSS-2 Bridge, an electronic device that was cleared for use in acupuncture in 2014. Now it is approved for reducing the symptoms of opioid withdrawal.

The NSS-2 Bridge is a small electrical nerve stimulator placed behind a patient’s ear. A battery-powered chip sends electrical pulses to stimulate branches of certain cranial nerves. Patients can use the device for up to 5 days during the acute phase of physical withdrawal.

The approval was based on results from a clinical study of 73 patients in withdrawal, evaluating their symptoms on the Clinical Opiate Withdrawal Scale (COWS), which measures signs and symptoms such as resting pulse rate, sweating, pupil size, gastrointestinal issues, bone and joint aches, tremors, and anxiety. The COWS scores range from 0 to > 36. The higher the score, the more severe the symptoms.

Before patients used the device, their average COWS score was 20.1. Within 30 minutes, all patient scores dropped by at least 31%. Nearly all (88%) the patients transitioned to medication-assisted therapy after 5 days of using the device.

You know that good feeling you get when you think about what you do for a living? That’s job satisfaction. So, what contributes to that feeling? Why does it matter?

Job satisfaction among both NPs and PAs remains high since last year’s survey.

The major determinants of job satisfaction include autonomy, appropriate pay, having adequate time to interact with patients, collegial support, and opportunities for professional growth.^1-3

Dissatisfaction—due, for example, to work-life imbalance, adverse working conditions, or threat of malpractice lawsuits—may motivate experienced clinicians to leave their jobs. Clearly, keeping NPs and PAs engaged and satisfied is key to creating and retaining effective health care teams, resulting in better patient care and lower health care costs.^1,4

So, are you interested in discovering ways to increase your career satisfaction? Actively seeking a new position? Looking to hire or retain staff? Check out the PDF for information on pay, benefits, and reasons your peers leave their jobs—broken out by profession and by region.

You know that good feeling you get when you think about what you do for a living? That’s job satisfaction. So, what contributes to that feeling? Why does it matter?

Job satisfaction among both NPs and PAs remains high since last year’s survey.

The major determinants of job satisfaction include autonomy, appropriate pay, having adequate time to interact with patients, collegial support, and opportunities for professional growth.^1-3

Dissatisfaction—due, for example, to work-life imbalance, adverse working conditions, or threat of malpractice lawsuits—may motivate experienced clinicians to leave their jobs. Clearly, keeping NPs and PAs engaged and satisfied is key to creating and retaining effective health care teams, resulting in better patient care and lower health care costs.^1,4

So, are you interested in discovering ways to increase your career satisfaction? Actively seeking a new position? Looking to hire or retain staff? Check out the PDF for information on pay, benefits, and reasons your peers leave their jobs—broken out by profession and by region.

You know that good feeling you get when you think about what you do for a living? That’s job satisfaction. So, what contributes to that feeling? Why does it matter?

Job satisfaction among both NPs and PAs remains high since last year’s survey.

The major determinants of job satisfaction include autonomy, appropriate pay, having adequate time to interact with patients, collegial support, and opportunities for professional growth.^1-3

Dissatisfaction—due, for example, to work-life imbalance, adverse working conditions, or threat of malpractice lawsuits—may motivate experienced clinicians to leave their jobs. Clearly, keeping NPs and PAs engaged and satisfied is key to creating and retaining effective health care teams, resulting in better patient care and lower health care costs.^1,4

So, are you interested in discovering ways to increase your career satisfaction? Actively seeking a new position? Looking to hire or retain staff? Check out the PDF for information on pay, benefits, and reasons your peers leave their jobs—broken out by profession and by region.

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Maria-Victoria Mateos, MD, PhD

ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.

The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).

D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.

“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.

“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”

Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.

Patients and treatment

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).

All patients received up to 9 cycles of VMP:

• Bortezomib at 1.3 mg/m² twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
• Melphalan at 9 mg/m² once daily on days 1 to 4 of each cycle
• Prednisone at 60 mg/m² once daily on days 1 to 4 of each cycle.

Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.

Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.

Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.

The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.

Response and survival

“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.

The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.

The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).

The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.

The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.

Adverse events

The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).

The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.

Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.

Lichen planus (LP) is a chronic inflammatory dermatosis of unknown origin that involves the skin and mucous membranes, and lichenoid drug eruption (LDE) is an uncommon cutaneous adverse reaction to a medication.¹ The manifestations resemble each other clinically, and sometimes it is difficult to differentiate between them on histology. The pathogenesis still is not well characterized, especially the key initiating event that leads to the development of LP or LDE postimmunization. There have been reports of LP or LDEs after certain vaccines, especially the hepatitis B and influenza vaccines.^2-4 Both vaccines are routinely administered in the United States; more than 100 million individuals have received the hepatitis B vaccine in the United States since it became available in 1982,⁵ and the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) recommends that all individuals 6 months or older receive an influenza vaccine every year.⁶ Currently, influenza vaccine coverage among adults 18 years or older reaches approximately 40% annually in the United States.⁶

Although certain viral infections (eg, hepatitis C virus) seem to play a role in the development of LP,^7,8 the link between LP and hepatitis B vaccination is less well recognized. Reports of LP and LDE after vaccination have been largely limited to case reports and case series.^2-4,9,10 Therefore, we aimed to characterize and review cases of LP and LDE following vaccination by analyzing the Vaccine Adverse Event Reporting System (VAERS) database.

Methods

The VAERS is a national vaccine safety surveillance database maintained jointly by the CDC and the US Food and Drug Administration to analyze adverse events (AEs) following immunizations. Serious AEs and deaths recorded in the VAERS were followed up periodically by VAERS staff. Information on vaccine-associated LP or LDE was retrieved from the VAERS database using the CDC WONDER online interface (http://wonder.cdc.gov/vaers.html). To examine if LP or LDE after vaccination occurred more frequently in patients with certain demographic risk factors, all reported cases of LP and LDE associated with vaccines administered from July 1990 to November 2014 were identified in the symptoms section of the VAERS system using the search terms lichen planus, oral lichen planus, and lichenoid drug eruption. Characteristics such as age, gender, time to onset, type of vaccine, method of diagnosis, and clinical outcome were collected.

The statistical package for social sciences (SPSS version 22) was utilized for the descriptive analysis. Fisher exact and χ² tests were used to evaluate statistical significance. A 2-sided P value of <.05 was considered statistically significant.

Results

There were 434,943 reported AEs following vaccination in the VAERS database from July 1990 to November 2014; among them, 33 cases involved LP or LDE. Of these vaccine-associated AEs, LP was diagnosed in 23 (69.7%) cases, while LDE and oral LP were diagnosed in 6 (18.2%) and 4 (12.1%) cases, respectively. Females represented slightly more than half (57.6% [19/33]) of the total cases. The median age of onset was 47 years. Approximately two-thirds of the identified cases were confirmed on skin biopsy and histology, while the rest were diagnosed either by a dermatologist or a primary care physician. The time to onset of symptoms ranged from 1 to 297 days after vaccination, with a median time of 14 days.

Patients with LP or LDE were significantly older compared to the reported AEs overall (P<.001); the median age of onset was 47 years for LP or LDE compared to 24 years for all reported AEs. Table 1 shows the various vaccines associated with LP or LDE. The hepatitis B, influenza, and herpes zoster vaccines were the 3 most common types of vaccines associated with these conditions. The hepatitis B vaccine accounted for 24.2% (8/33) of the reported events, followed by influenza (18.2% [6/33]) and herpes zoster (15.2% [5/33]) vaccines. In addition, there were 3 cases of cutaneous reaction after receiving the combination hepatitis A and hepatitis B vaccine. Table 2 presents details of the reported events associated with hepatitis B, influenza, herpes zoster, combination hepatitis A and hepatitis B, and hepatitis A vaccination.

Of 8 AEs associated with hepatitis B vaccination, 1 AE resulted in permanent disability and required hospitalization. Of 5 cases of AEs associated with herpes zoster vaccination, 1 AE resulted in permanent disability.

Comment

The estimated prevalence of LP ranges from 0.22% to 5% worldwide,^11-15 with an incidence of 0.032% to 0.037%.¹⁶ Although rare, LP and LDE can occur from certain medications or vaccines. Cases of LP have been reported after hepatitis B and influenza vaccinations. The first case of LP following hepatitis B vaccination was described by Ciaccio and Rebora¹⁷ in 1990. Since then, a total of 50 similar cases have been reported worldwide.² There also have been reports of LP following influenza, tetanus-diphtheria-pertussis, measles-mumps-rubella, and inactivated polio vaccines.^3,4,9,10 Table 3 summarizes cases of LP following various vaccinations.

The key initiating event of the pathogenesis for both LP and LDE is not completely understood. Both conditions share similar immunologic mechanisms of persistently activated CD8 autocytotoxic T lymphocytes against epidermal cells.¹⁸ These cells can induce apoptosis of basal epidermal keratinocytes and generate various cytokines (eg, IFN-γ, IL-5) to enhance expression of class II MHC molecules and antigen presentation to CD4 T cells.^19-22 It is conceivable that one of the initiating factors may be related to components in vaccines.

Hepatitis B, influenza, and herpes zoster vaccines were the 3 most common vaccines implicated in postimmunization LP or LDEs in our study. The excipients of these vaccines were compared based on the product inserts to identify any common components. It was found that all 3 vaccines contain either yeast protein or egg protein with various forms of phosphate buffers, while the hepatitis A and herpes zoster vaccines share Medical Research Council cell strain 5 (human diploid) cells as well as other cellular components.²³ Sato et al⁴ suggested that specific vaccine components, such as the vaccine itself or egg proteins, could have contributed to the development of LP following vaccination. It has been postulated that the protein S fraction of hepatitis B surface antigen plays a crucial role in the pathogenesis of both LP and LDE after hepatitis B vaccination.^2,24 It is likely that protein S shares common epitopes on keratinocytes that are recognized by the immune system, thus activating cytotoxic T lymphocytes and inducing apoptosis.^2,24

In this study, the median time to onset of vaccine-related LP was 14 days, which is consistent with a case series by Sato et al,⁴ suggesting that adverse reactions mainly occurred within 2 weeks after influenza vaccination. Onset of symptoms within 2 weeks of vaccination would therefore be a crucial clue for diagnosing possible vaccine-related LP or LDE. On the other hand, at least 4 patients in our study had onset of LP and LDE more than 1 month after vaccination; 2 of 4 cases even reported symptom onset at 175 and 297 days after hepatitis B vaccination, which were much longer than the 120 days reported by Tarakji et al.² It is not known if these cases constitute true vaccine-associated LP or LDE or if unmeasured confounding factors such as concurrent medications or comorbidities may have contributed to the development of these AEs.

It also is interesting to note that LP and LDE affected mainly middle-aged women. An increased risk of autoimmunity in female adults partly explains this observation.²⁵ Some vaccines, such as herpes zoster and influenza vaccines, generally are recommended for older adults who also are more likely to have multiple comorbidities or take multiple medications/supplements, which can potentially skew the prevalence of AEs toward an older age group. It should be noted, however, that LP and LDE were relatively uncommon AEs following vaccination in the current study. In this study, LP and LDE consisted of only 0.01% (N=42,230) of all AEs after hepatitis B vaccination, while the more common AEs such as pyrexia, nonspecific rashes, nonspecific gastrointestinal symptoms, and headache contributed to approximately 66.5% of all reported events.

One of the strengths of our study is that up to two-thirds of cases were confirmed histologically and all patients were seen and followed up by dermatologists or physicians. The VAERS is an easily accessible, up-to-date, and live reporting system that collects all AEs associated with vaccines in the United States. Important clinical and laboratory information usually is available in the database; however, the main limitation is that this study can only demonstrate a possible association but not a causal relationship between vaccination and LP or LDE. There can be various sources of biases such as underreporting, overreporting, or inaccurate reporting.^26,27 Pertinent clinical information (eg, new medications, new dental fillings/implants) that could potentially misrepresent the actual relationship between vaccination and development of AEs also was not available in the VAERS database. A cohort study with long-term follow-up or a large-scale case-control study would be useful in evaluating such associations.

Conclusion

Lichen planus and LDE can occur, albeit rarely, after vaccination, especially following hepatitis B vaccination. When middle-aged adults present to the clinic with LP or LDE, it is important to inquire about recent vaccination history in addition to a detailed medication history.

Lichen planus (LP) is a chronic inflammatory dermatosis of unknown origin that involves the skin and mucous membranes, and lichenoid drug eruption (LDE) is an uncommon cutaneous adverse reaction to a medication.¹ The manifestations resemble each other clinically, and sometimes it is difficult to differentiate between them on histology. The pathogenesis still is not well characterized, especially the key initiating event that leads to the development of LP or LDE postimmunization. There have been reports of LP or LDEs after certain vaccines, especially the hepatitis B and influenza vaccines.^2-4 Both vaccines are routinely administered in the United States; more than 100 million individuals have received the hepatitis B vaccine in the United States since it became available in 1982,⁵ and the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) recommends that all individuals 6 months or older receive an influenza vaccine every year.⁶ Currently, influenza vaccine coverage among adults 18 years or older reaches approximately 40% annually in the United States.⁶

Although certain viral infections (eg, hepatitis C virus) seem to play a role in the development of LP,^7,8 the link between LP and hepatitis B vaccination is less well recognized. Reports of LP and LDE after vaccination have been largely limited to case reports and case series.^2-4,9,10 Therefore, we aimed to characterize and review cases of LP and LDE following vaccination by analyzing the Vaccine Adverse Event Reporting System (VAERS) database.

Methods

The VAERS is a national vaccine safety surveillance database maintained jointly by the CDC and the US Food and Drug Administration to analyze adverse events (AEs) following immunizations. Serious AEs and deaths recorded in the VAERS were followed up periodically by VAERS staff. Information on vaccine-associated LP or LDE was retrieved from the VAERS database using the CDC WONDER online interface (http://wonder.cdc.gov/vaers.html). To examine if LP or LDE after vaccination occurred more frequently in patients with certain demographic risk factors, all reported cases of LP and LDE associated with vaccines administered from July 1990 to November 2014 were identified in the symptoms section of the VAERS system using the search terms lichen planus, oral lichen planus, and lichenoid drug eruption. Characteristics such as age, gender, time to onset, type of vaccine, method of diagnosis, and clinical outcome were collected.

The statistical package for social sciences (SPSS version 22) was utilized for the descriptive analysis. Fisher exact and χ² tests were used to evaluate statistical significance. A 2-sided P value of <.05 was considered statistically significant.

Results

There were 434,943 reported AEs following vaccination in the VAERS database from July 1990 to November 2014; among them, 33 cases involved LP or LDE. Of these vaccine-associated AEs, LP was diagnosed in 23 (69.7%) cases, while LDE and oral LP were diagnosed in 6 (18.2%) and 4 (12.1%) cases, respectively. Females represented slightly more than half (57.6% [19/33]) of the total cases. The median age of onset was 47 years. Approximately two-thirds of the identified cases were confirmed on skin biopsy and histology, while the rest were diagnosed either by a dermatologist or a primary care physician. The time to onset of symptoms ranged from 1 to 297 days after vaccination, with a median time of 14 days.

Patients with LP or LDE were significantly older compared to the reported AEs overall (P<.001); the median age of onset was 47 years for LP or LDE compared to 24 years for all reported AEs. Table 1 shows the various vaccines associated with LP or LDE. The hepatitis B, influenza, and herpes zoster vaccines were the 3 most common types of vaccines associated with these conditions. The hepatitis B vaccine accounted for 24.2% (8/33) of the reported events, followed by influenza (18.2% [6/33]) and herpes zoster (15.2% [5/33]) vaccines. In addition, there were 3 cases of cutaneous reaction after receiving the combination hepatitis A and hepatitis B vaccine. Table 2 presents details of the reported events associated with hepatitis B, influenza, herpes zoster, combination hepatitis A and hepatitis B, and hepatitis A vaccination.

Of 8 AEs associated with hepatitis B vaccination, 1 AE resulted in permanent disability and required hospitalization. Of 5 cases of AEs associated with herpes zoster vaccination, 1 AE resulted in permanent disability.

Comment

The estimated prevalence of LP ranges from 0.22% to 5% worldwide,^11-15 with an incidence of 0.032% to 0.037%.¹⁶ Although rare, LP and LDE can occur from certain medications or vaccines. Cases of LP have been reported after hepatitis B and influenza vaccinations. The first case of LP following hepatitis B vaccination was described by Ciaccio and Rebora¹⁷ in 1990. Since then, a total of 50 similar cases have been reported worldwide.² There also have been reports of LP following influenza, tetanus-diphtheria-pertussis, measles-mumps-rubella, and inactivated polio vaccines.^3,4,9,10 Table 3 summarizes cases of LP following various vaccinations.

The key initiating event of the pathogenesis for both LP and LDE is not completely understood. Both conditions share similar immunologic mechanisms of persistently activated CD8 autocytotoxic T lymphocytes against epidermal cells.¹⁸ These cells can induce apoptosis of basal epidermal keratinocytes and generate various cytokines (eg, IFN-γ, IL-5) to enhance expression of class II MHC molecules and antigen presentation to CD4 T cells.^19-22 It is conceivable that one of the initiating factors may be related to components in vaccines.

Hepatitis B, influenza, and herpes zoster vaccines were the 3 most common vaccines implicated in postimmunization LP or LDEs in our study. The excipients of these vaccines were compared based on the product inserts to identify any common components. It was found that all 3 vaccines contain either yeast protein or egg protein with various forms of phosphate buffers, while the hepatitis A and herpes zoster vaccines share Medical Research Council cell strain 5 (human diploid) cells as well as other cellular components.²³ Sato et al⁴ suggested that specific vaccine components, such as the vaccine itself or egg proteins, could have contributed to the development of LP following vaccination. It has been postulated that the protein S fraction of hepatitis B surface antigen plays a crucial role in the pathogenesis of both LP and LDE after hepatitis B vaccination.^2,24 It is likely that protein S shares common epitopes on keratinocytes that are recognized by the immune system, thus activating cytotoxic T lymphocytes and inducing apoptosis.^2,24

In this study, the median time to onset of vaccine-related LP was 14 days, which is consistent with a case series by Sato et al,⁴ suggesting that adverse reactions mainly occurred within 2 weeks after influenza vaccination. Onset of symptoms within 2 weeks of vaccination would therefore be a crucial clue for diagnosing possible vaccine-related LP or LDE. On the other hand, at least 4 patients in our study had onset of LP and LDE more than 1 month after vaccination; 2 of 4 cases even reported symptom onset at 175 and 297 days after hepatitis B vaccination, which were much longer than the 120 days reported by Tarakji et al.² It is not known if these cases constitute true vaccine-associated LP or LDE or if unmeasured confounding factors such as concurrent medications or comorbidities may have contributed to the development of these AEs.

It also is interesting to note that LP and LDE affected mainly middle-aged women. An increased risk of autoimmunity in female adults partly explains this observation.²⁵ Some vaccines, such as herpes zoster and influenza vaccines, generally are recommended for older adults who also are more likely to have multiple comorbidities or take multiple medications/supplements, which can potentially skew the prevalence of AEs toward an older age group. It should be noted, however, that LP and LDE were relatively uncommon AEs following vaccination in the current study. In this study, LP and LDE consisted of only 0.01% (N=42,230) of all AEs after hepatitis B vaccination, while the more common AEs such as pyrexia, nonspecific rashes, nonspecific gastrointestinal symptoms, and headache contributed to approximately 66.5% of all reported events.

One of the strengths of our study is that up to two-thirds of cases were confirmed histologically and all patients were seen and followed up by dermatologists or physicians. The VAERS is an easily accessible, up-to-date, and live reporting system that collects all AEs associated with vaccines in the United States. Important clinical and laboratory information usually is available in the database; however, the main limitation is that this study can only demonstrate a possible association but not a causal relationship between vaccination and LP or LDE. There can be various sources of biases such as underreporting, overreporting, or inaccurate reporting.^26,27 Pertinent clinical information (eg, new medications, new dental fillings/implants) that could potentially misrepresent the actual relationship between vaccination and development of AEs also was not available in the VAERS database. A cohort study with long-term follow-up or a large-scale case-control study would be useful in evaluating such associations.

Conclusion

Lichen planus and LDE can occur, albeit rarely, after vaccination, especially following hepatitis B vaccination. When middle-aged adults present to the clinic with LP or LDE, it is important to inquire about recent vaccination history in addition to a detailed medication history.

Lichen planus (LP) is a chronic inflammatory dermatosis of unknown origin that involves the skin and mucous membranes, and lichenoid drug eruption (LDE) is an uncommon cutaneous adverse reaction to a medication.¹ The manifestations resemble each other clinically, and sometimes it is difficult to differentiate between them on histology. The pathogenesis still is not well characterized, especially the key initiating event that leads to the development of LP or LDE postimmunization. There have been reports of LP or LDEs after certain vaccines, especially the hepatitis B and influenza vaccines.^2-4 Both vaccines are routinely administered in the United States; more than 100 million individuals have received the hepatitis B vaccine in the United States since it became available in 1982,⁵ and the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) recommends that all individuals 6 months or older receive an influenza vaccine every year.⁶ Currently, influenza vaccine coverage among adults 18 years or older reaches approximately 40% annually in the United States.⁶

Although certain viral infections (eg, hepatitis C virus) seem to play a role in the development of LP,^7,8 the link between LP and hepatitis B vaccination is less well recognized. Reports of LP and LDE after vaccination have been largely limited to case reports and case series.^2-4,9,10 Therefore, we aimed to characterize and review cases of LP and LDE following vaccination by analyzing the Vaccine Adverse Event Reporting System (VAERS) database.

Methods

The VAERS is a national vaccine safety surveillance database maintained jointly by the CDC and the US Food and Drug Administration to analyze adverse events (AEs) following immunizations. Serious AEs and deaths recorded in the VAERS were followed up periodically by VAERS staff. Information on vaccine-associated LP or LDE was retrieved from the VAERS database using the CDC WONDER online interface (http://wonder.cdc.gov/vaers.html). To examine if LP or LDE after vaccination occurred more frequently in patients with certain demographic risk factors, all reported cases of LP and LDE associated with vaccines administered from July 1990 to November 2014 were identified in the symptoms section of the VAERS system using the search terms lichen planus, oral lichen planus, and lichenoid drug eruption. Characteristics such as age, gender, time to onset, type of vaccine, method of diagnosis, and clinical outcome were collected.

The statistical package for social sciences (SPSS version 22) was utilized for the descriptive analysis. Fisher exact and χ² tests were used to evaluate statistical significance. A 2-sided P value of <.05 was considered statistically significant.

Results

There were 434,943 reported AEs following vaccination in the VAERS database from July 1990 to November 2014; among them, 33 cases involved LP or LDE. Of these vaccine-associated AEs, LP was diagnosed in 23 (69.7%) cases, while LDE and oral LP were diagnosed in 6 (18.2%) and 4 (12.1%) cases, respectively. Females represented slightly more than half (57.6% [19/33]) of the total cases. The median age of onset was 47 years. Approximately two-thirds of the identified cases were confirmed on skin biopsy and histology, while the rest were diagnosed either by a dermatologist or a primary care physician. The time to onset of symptoms ranged from 1 to 297 days after vaccination, with a median time of 14 days.

Patients with LP or LDE were significantly older compared to the reported AEs overall (P<.001); the median age of onset was 47 years for LP or LDE compared to 24 years for all reported AEs. Table 1 shows the various vaccines associated with LP or LDE. The hepatitis B, influenza, and herpes zoster vaccines were the 3 most common types of vaccines associated with these conditions. The hepatitis B vaccine accounted for 24.2% (8/33) of the reported events, followed by influenza (18.2% [6/33]) and herpes zoster (15.2% [5/33]) vaccines. In addition, there were 3 cases of cutaneous reaction after receiving the combination hepatitis A and hepatitis B vaccine. Table 2 presents details of the reported events associated with hepatitis B, influenza, herpes zoster, combination hepatitis A and hepatitis B, and hepatitis A vaccination.

Of 8 AEs associated with hepatitis B vaccination, 1 AE resulted in permanent disability and required hospitalization. Of 5 cases of AEs associated with herpes zoster vaccination, 1 AE resulted in permanent disability.

Comment

The estimated prevalence of LP ranges from 0.22% to 5% worldwide,^11-15 with an incidence of 0.032% to 0.037%.¹⁶ Although rare, LP and LDE can occur from certain medications or vaccines. Cases of LP have been reported after hepatitis B and influenza vaccinations. The first case of LP following hepatitis B vaccination was described by Ciaccio and Rebora¹⁷ in 1990. Since then, a total of 50 similar cases have been reported worldwide.² There also have been reports of LP following influenza, tetanus-diphtheria-pertussis, measles-mumps-rubella, and inactivated polio vaccines.^3,4,9,10 Table 3 summarizes cases of LP following various vaccinations.

The key initiating event of the pathogenesis for both LP and LDE is not completely understood. Both conditions share similar immunologic mechanisms of persistently activated CD8 autocytotoxic T lymphocytes against epidermal cells.¹⁸ These cells can induce apoptosis of basal epidermal keratinocytes and generate various cytokines (eg, IFN-γ, IL-5) to enhance expression of class II MHC molecules and antigen presentation to CD4 T cells.^19-22 It is conceivable that one of the initiating factors may be related to components in vaccines.

Hepatitis B, influenza, and herpes zoster vaccines were the 3 most common vaccines implicated in postimmunization LP or LDEs in our study. The excipients of these vaccines were compared based on the product inserts to identify any common components. It was found that all 3 vaccines contain either yeast protein or egg protein with various forms of phosphate buffers, while the hepatitis A and herpes zoster vaccines share Medical Research Council cell strain 5 (human diploid) cells as well as other cellular components.²³ Sato et al⁴ suggested that specific vaccine components, such as the vaccine itself or egg proteins, could have contributed to the development of LP following vaccination. It has been postulated that the protein S fraction of hepatitis B surface antigen plays a crucial role in the pathogenesis of both LP and LDE after hepatitis B vaccination.^2,24 It is likely that protein S shares common epitopes on keratinocytes that are recognized by the immune system, thus activating cytotoxic T lymphocytes and inducing apoptosis.^2,24

In this study, the median time to onset of vaccine-related LP was 14 days, which is consistent with a case series by Sato et al,⁴ suggesting that adverse reactions mainly occurred within 2 weeks after influenza vaccination. Onset of symptoms within 2 weeks of vaccination would therefore be a crucial clue for diagnosing possible vaccine-related LP or LDE. On the other hand, at least 4 patients in our study had onset of LP and LDE more than 1 month after vaccination; 2 of 4 cases even reported symptom onset at 175 and 297 days after hepatitis B vaccination, which were much longer than the 120 days reported by Tarakji et al.² It is not known if these cases constitute true vaccine-associated LP or LDE or if unmeasured confounding factors such as concurrent medications or comorbidities may have contributed to the development of these AEs.

It also is interesting to note that LP and LDE affected mainly middle-aged women. An increased risk of autoimmunity in female adults partly explains this observation.²⁵ Some vaccines, such as herpes zoster and influenza vaccines, generally are recommended for older adults who also are more likely to have multiple comorbidities or take multiple medications/supplements, which can potentially skew the prevalence of AEs toward an older age group. It should be noted, however, that LP and LDE were relatively uncommon AEs following vaccination in the current study. In this study, LP and LDE consisted of only 0.01% (N=42,230) of all AEs after hepatitis B vaccination, while the more common AEs such as pyrexia, nonspecific rashes, nonspecific gastrointestinal symptoms, and headache contributed to approximately 66.5% of all reported events.

One of the strengths of our study is that up to two-thirds of cases were confirmed histologically and all patients were seen and followed up by dermatologists or physicians. The VAERS is an easily accessible, up-to-date, and live reporting system that collects all AEs associated with vaccines in the United States. Important clinical and laboratory information usually is available in the database; however, the main limitation is that this study can only demonstrate a possible association but not a causal relationship between vaccination and LP or LDE. There can be various sources of biases such as underreporting, overreporting, or inaccurate reporting.^26,27 Pertinent clinical information (eg, new medications, new dental fillings/implants) that could potentially misrepresent the actual relationship between vaccination and development of AEs also was not available in the VAERS database. A cohort study with long-term follow-up or a large-scale case-control study would be useful in evaluating such associations.

Conclusion

Lichen planus and LDE can occur, albeit rarely, after vaccination, especially following hepatitis B vaccination. When middle-aged adults present to the clinic with LP or LDE, it is important to inquire about recent vaccination history in addition to a detailed medication history.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

Atlanta – Adding caplacizumab, an anti–Von Willebrand Factor humanized single variable domain immunoglobulin, to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly hastened platelet normalization and improved several key clinical endpoints in a pivotal randomized placebo-controlled phase 3 trial of 145 patients (HERCULES).

At any given time, platelet normalization was 55% more likely with caplacizumab (10 mg) versus placebo (platelet normalization rate ratio, 1.55; 95% confidence interval, 1.10-2.20; P less than .01), Marie Scully, MD, reported in late-breaking oral presentation at the annual meeting of the American Society for Hematology.Caplacizumab also significantly reduced the rate of aTTP recurrence, compared with placebo (13% vs. 38%; P less than .001) and cut days of plasma exchange, plasma volume, and ICU and hospital stays by 31% to 65%, compared with placebo, reported Dr. Scully of University College Hospital, London, UK. HERCULES enrolled patients with an acute episode of aTTP and at least one prior plasma exchange (PE). Patients received caplacizumab (10 mg) or placebo plus daily PE plus corticosteroids. The caplacizumab group received a single IV dose before their first on-study PE followed by daily subcutaneous doses during PE therapy and for 30 days afterward.

Phase 2 data on aTTP earned caplacizumab fast track designation from the Food and Drug Administration in July 2017. In this video, Dr. Scully highlights key findings of the phase 3 HERCULES trial and discusses how physicians could integrate caplacizumab into their current aTTP treatment approach.

HERCULES was sponsored by Ablynx. Dr. Scully disclosed honoraria and research funding from Ablynx, Shire, Novartis, and Alexion.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.

When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.

“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”

Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”

However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”

The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.

But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.

In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.

A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.

For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.

The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.

The authors had no relevant financial disclosures

SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.

This product, glycopyrrolate, has specifically been approved for use as a long-term maintenance treatment of air-flow obstruction in patients with COPD. Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.

[email protected]

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

[email protected]

SOURCE: FDA.gov

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

[email protected]

SOURCE: FDA.gov

The Food and Drug Administration announced Dec. 12 the approval of mepolizumab (Nucala) to treat adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), making it the first FDA-approved therapy intended to treat this rare disease.

Approval was based on data from a 52-week clinical trial that compared mepolizumab with placebo, according to the FDA. Patients received 300 mg of mepolizumab once every 4 weeks while continuing stable daily oral corticosteroid therapy. Those patients receiving mepolizumab “achieved a significantly greater accrued time in remission compared with placebo,” and a significantly higher proportion of patients receiving 300 mg of mepolizumab had achieved remission at week 36 and week 48, the statement said. Additionally, significantly more patients treated with mepolizumab achieved remission within the first 24 weeks and remained in remission for the remainder of the 52-week study treatment period.

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SOURCE: FDA.gov

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

The National Institutes of Health has launched two large HIV clinical trials in Africa: one to investigate the efficacy of a long-acting injectable anti-HIV drug and one to test an experimental new HIV vaccine.

The first is a phase 3 trial comparing an injectable version of the investigational integrase inhibitor cabotegravir with pre-exposure prophylaxis (PrEP) using daily oral Truvada (emtricitabine). Researchers aim to recruit 3,200 sexually active women from across Southern and Eastern Africa, and follow them for an average of 2.6 years.

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]

Recently I mentioned RSS news feeds as a useful, versatile online tool, but because it has been a while since I’ve discussed RSS feeds, an update is certainly in order.

The sheer volume of information on the web makes quick and efficient searching an indispensable skill, but once you have become quick and efficient at finding the information you need, a new problem arises: The information changes! All the good medical, news, and other information-based websites change and update their content on a regular, but unpredictable basis. And checking each one for new information can be very tedious, if you can remember to do it at all.

Many sites offer an e-mail service to notify you of new content, but multiple e-mail subscriptions clutter your inbox and often can’t select out the information you’re really interested in. RSS feeds are a more efficient and increasingly popular method of staying current on all the subjects that interest you – medical and otherwise. RSS (which stands for “Rich Site Summary” or “Really Simple Syndication,” depending on whom you ask) is a file format, and websites use that format (or a similar one called Atom) to produce a summary file, or “feed,” of new content, along with links to full versions of that content. When you subscribe to a given website’s feed, you’ll receive a summary of new content each time the website is updated.

Thousands of websites now offer RSS feeds, including most of the large medical information services, all the major news organizations, and many web logs.

FotoMaximum/Thinkstock

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected]