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FDA grants orphan designation to product for CMV
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products 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 ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products 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 ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products 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.
SCD drug receives rare pediatric disease designation
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
FDA grants orphan designation to product for GVHD
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products 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 ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products 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 ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products 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.
Respiratory infections in early years of life linked to celiac disease
in those with a family history of CD, according to Renata Auricchio, MD, University of Naples (Italy) Federico II, and her associates.
In a prospective cohort study, 373 newborns from families with at least one relative with CD were recruited. The cumulative incidence of new cases of CD was 6% at 3 years and 13.5% at 5 years of age, the researchers noted. In the first year when no child produced anti-tissue transglutaminase (anti-tTG) antibodies, respiratory infections (upper and lower tract) were more common among the case patients than among the controls (58% vs. 40%). During the second year, respiratory infections were again more frequent among the case patients than among controls (52% vs. 32%). And in the third year of life when most of the case patients were diagnosed with CD, no clinical event was more frequent in the case patients than in the control group.
“In this study, we report that early infections significantly contribute to the risk of developing CD,” Dr. Auricchio and her associates concluded. “It is possible that the exposure to early infection stimulates a genetically predisposed immune profile, which contributes to the switch from tolerance to intolerance to gluten, which is a common food antigen.”
Read the full study in Pediatrics (doi: 10.1542/peds.2016-4102).
in those with a family history of CD, according to Renata Auricchio, MD, University of Naples (Italy) Federico II, and her associates.
In a prospective cohort study, 373 newborns from families with at least one relative with CD were recruited. The cumulative incidence of new cases of CD was 6% at 3 years and 13.5% at 5 years of age, the researchers noted. In the first year when no child produced anti-tissue transglutaminase (anti-tTG) antibodies, respiratory infections (upper and lower tract) were more common among the case patients than among the controls (58% vs. 40%). During the second year, respiratory infections were again more frequent among the case patients than among controls (52% vs. 32%). And in the third year of life when most of the case patients were diagnosed with CD, no clinical event was more frequent in the case patients than in the control group.
“In this study, we report that early infections significantly contribute to the risk of developing CD,” Dr. Auricchio and her associates concluded. “It is possible that the exposure to early infection stimulates a genetically predisposed immune profile, which contributes to the switch from tolerance to intolerance to gluten, which is a common food antigen.”
Read the full study in Pediatrics (doi: 10.1542/peds.2016-4102).
in those with a family history of CD, according to Renata Auricchio, MD, University of Naples (Italy) Federico II, and her associates.
In a prospective cohort study, 373 newborns from families with at least one relative with CD were recruited. The cumulative incidence of new cases of CD was 6% at 3 years and 13.5% at 5 years of age, the researchers noted. In the first year when no child produced anti-tissue transglutaminase (anti-tTG) antibodies, respiratory infections (upper and lower tract) were more common among the case patients than among the controls (58% vs. 40%). During the second year, respiratory infections were again more frequent among the case patients than among controls (52% vs. 32%). And in the third year of life when most of the case patients were diagnosed with CD, no clinical event was more frequent in the case patients than in the control group.
“In this study, we report that early infections significantly contribute to the risk of developing CD,” Dr. Auricchio and her associates concluded. “It is possible that the exposure to early infection stimulates a genetically predisposed immune profile, which contributes to the switch from tolerance to intolerance to gluten, which is a common food antigen.”
Read the full study in Pediatrics (doi: 10.1542/peds.2016-4102).
FROM PEDIATRICS
Total Eclipse of the Heart
ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm. Normal sinus rhythm is evidenced by normal-appearing P waves at a rate of about 66 beats/min, although there is some respiratory variation. There is no correlation of the P waves to the QRS complex. A junctional rhythm is diagnosed based on narrow QRS complexes of normal duration (82 ms). The patient underwent implantation of a dual-chamber pacemaker and had a complete recovery.
ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm. Normal sinus rhythm is evidenced by normal-appearing P waves at a rate of about 66 beats/min, although there is some respiratory variation. There is no correlation of the P waves to the QRS complex. A junctional rhythm is diagnosed based on narrow QRS complexes of normal duration (82 ms). The patient underwent implantation of a dual-chamber pacemaker and had a complete recovery.
ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm. Normal sinus rhythm is evidenced by normal-appearing P waves at a rate of about 66 beats/min, although there is some respiratory variation. There is no correlation of the P waves to the QRS complex. A junctional rhythm is diagnosed based on narrow QRS complexes of normal duration (82 ms). The patient underwent implantation of a dual-chamber pacemaker and had a complete recovery.
For the past two months, a 72-year-old man has been experiencing dyspnea on exertion “off and on.” In the past three days, this shortness of breath has been more consistent.
When his son drops by to check on him, the father mentions the problem, noting that although he’s usually quite active, he hasn’t “had the stamina” to finish his current woodworking project. The son, a paramedic, checks his father’s pulse; it is regular, but the rate is below 40 beats/min. The son decides to bring him to the emergency department for evaluation.
His medical history is remarkable for hypertension, gout, and cholelithiasis. He underwent a right orchiectomy secondary to trauma in the remote past and had bilateral total knee replacements four years ago. Since the latter procedure, he has been extremely active; prior to his current complaint, he walked three miles each day.
The patient, a retired minister, lost his wife to cancer four years ago and now lives at home alone. He has four sons—one of whom visits twice a week—and two daughters, all of whom are in good health. He has never smoked and only drinks a glass of wine on holidays.
His current medications include metoprolol XL (25 mg/d) for hypertension and acetaminophen as needed for arthritic joint pain. He denies missing or doubling his medication doses. He is allergic to sulfa, which causes an anaphylactic reaction with significant airway narrowing.
The patient wears corrective lenses and hearing aids. He denies recent changes in bowel or bladder function, extreme temperature changes, productive cough, or constitutional symptoms suggestive of indolent infection.
Vital signs include a regular pulse of 50 beats/min; blood pressure, 104/66 mm Hg; respiratory rate, 14 breaths/min-1; and temperature, 98.4°F. His height is 70 in and his weight, 172 lb.
On physical exam, you notice that the patient tires walking 20 feet from the waiting room to the exam room. Otherwise, he is in no apparent distress. He denies chest pain with exertion or dyspnea at rest. His funduscopic exam is normal, his oropharynx is normal, and he is not missing teeth. There are no carotid bruits. The lungs are clear in all fields without evidence of rales, rhonchi, or crackles.
Cardiac exam reveals a grade II/VI early systolic murmur at the left upper sternal border, which does not radiate to the carotid arteries or the back. The abdomen is scaphoid and soft with no palpable masses. Peripheral pulses are strong bilaterally in all extremities. He has evidence of osteoarthritis in his hands and feet, as well as surgical scars consistent with knee replacements. His neurologic exam is intact.
An ECG reveals a ventricular rate of 47 beats/min; no discernable PR interval; QRS duration, 82 ms; QT/QTc interval, 450/398 ms; P axis, 48°; R axis, 14°; and T axis, 26°. What is your interpretation?
Trump administration ends DACA program, stranding medical students
President Trump has ended the Obama administration’s Deferred Action for Childhood Arrivals (DACA) program, a policy that protected immigrants who came to the United States as children from deportation and authorized them to work in the United States.
In a Sept. 5 press conference, Attorney General Jeff Sessions called the DACA program an unconstitutional overreach of executive branch power by the former administration that deliberately sought to undermine the legislative branch. Rollback of the DACA program will begin immediately, Mr. Sessions said, with the program expiring completely on March 5, 2018.
“The effect of this unilateral executive amnesty, among other things, contributed to a surge of minors at the southern border that yielded terrible humanitarian consequences,” Mr. Sessions said during the press conference. “[DACA has] also denied jobs to hundreds of thousands of Americans by allowing those same illegal aliens to take those jobs. To have a lawful system of immigration that serves the national interest, we cannot admit everyone. Therefore the nation must set and enforce a limit on how many immigrants we admit and that means all cannot be accepted.”
In a statement issued shortly after the press conference, President Trump said winding down the DACA program is in the nation’s best interest, and that there can be no principled immigration reform if the executive branch is able to “rewrite or nullify federal laws at will.
“As President, my highest duty is to defend the American people and the Constitution of the United States of America,” President Trump said in the statement. “At the same time, I do not favor punishing children, most of whom are now adults, for the actions of their parents. But we must also recognize that we are nation of opportunity because we are a nation of laws.”
The DACA program was created by the Obama administration in 2012 as a way of protecting young, undocumented immigrants from deportation after Congress repeatedly blocked legislation that would develop such a safe haven. The policy allowed about 800,000 young adults brought to the United States illegally as children to work legally in the U.S. and remain in the country without the fear of deportation.
The program’s end will affect the growing number of medical students with DACA status and likely jeopardize the funding invested in their training. Sixty-two medical schools accept applications from DACA applicants, according to the Association of American Medical Colleges (AAMC). For the 2016 -2017 school year, 113 students with DACA status applied to US medical schools, and there were 65 medical students enrolled who had DACA status. AAMC does not collect data on medical students with DACA status; the National Resident Matching Program, likewise, does not collect data on residents with DACA status.
Loyola University in Chicago is one institute that could be significantly impacted by recension of DACA. The university has accepted more students with DACA status than any other U.S. medical school, and currently has 32 DACA students attending, said Mark Kuczewski, Ph.D., chair of medical education at Loyola University.
“It’s a tragic decision,” he said in an interview. “It once again puts a cloud over these young people who DACA has given the first real opportunity to come out of the shadows, be educated, and serve the community. Now they’re returned back to the situation of uncertainty.”
The decision to end DACA means that current DACA medical students may not be able to finish their training and that those close to completion may not be able to use their degrees in the workforce, Dr. Kuczewski said. Since they are not citizens, DACA students do not qualify for federal student loans, so medical schools must find ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Loyola’s Stritch School of Medicine, Dr. Kuczewski said. However, such loan programs require DACA status. Without DACA or another path to citizenship, medical students in the middle of training will not be able to obtain financial aid to finish their training, he said. The work authorization that DACA provided will also be eliminated.
Dr. Kuczewski said his university plans to advocate strongly for Congress to pass legislation to protect DACA youth, such as the Dream Act of 2017.
“We are going to advocate strongly because we believe this is common sense,” he said. “You don’t just throw away the talents of these young people and the investments they’ve made in their education and the investments we’ve made in them. DACA has given many people the chance to see these young people as students, as employees, as colleagues, and we hope that helps people to mobilize.”
In a statement, Jack Ende, MD, president of the American College of Physicians, said President Trump’s decision to end the DACA program threatens to deny the country the talents of more than half a million individuals making enormous contributions and will also undermine public health and medical education.
“Today’s executive order has the potential to gravely impact public health,” Dr. Ende said in the statement. “We know that noncitizens and undocumented immigrants are more likely to lack health insurance coverage. If the nearly 800,000 people who are currently benefiting from DACA have their protections removed, many will avoid seeking health care in order to reduce the risk of detection and deportation. … Those who seek to serve in the health care professions will be denied that opportunity.”
The Immigration Reform Law Institute praised President Trump’s decision to rescind the DACA program, calling the policy an affront to Congress and a violation of the U.S. Constitution.
“Contrary to former President Obama’s claims, not only is DACA not authorized by federal statute, but prior to the unlawful program, deferred action has only ever been applied to small numbers of illegal aliens on a case-by-case basis,” Dale Wilcox, executive director, said in a statement. “Applying it to approximately 15% of the illegal alien population was never a proper exercise of the president’s discretion under the Constitution and is inconsistent with the president’s duty to take care that the laws be faithfully executed. By rescinding DACA, President Trump has put an end to the previous administration’s flagrant violation of our immigration laws and its abuse of hard-working American taxpayers.”
In a memorandum issued Sept. 5, the Department of Homeland Security said it will begin winding down the DACA program, while providing a limited window in which it will adjudicate certain requests for DACA and associated applications. DHS will adjudicate, on an individual, case-by-case basis, properly filed pending DACA initial requests and associated applications for employment authorization documents that have been accepted by the department as of Sept.5, 2017, according to the memorandum. All DACA initial requests and associated applications filed after this date will be rejected.
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On Twitter @legal_med
President Trump has ended the Obama administration’s Deferred Action for Childhood Arrivals (DACA) program, a policy that protected immigrants who came to the United States as children from deportation and authorized them to work in the United States.
In a Sept. 5 press conference, Attorney General Jeff Sessions called the DACA program an unconstitutional overreach of executive branch power by the former administration that deliberately sought to undermine the legislative branch. Rollback of the DACA program will begin immediately, Mr. Sessions said, with the program expiring completely on March 5, 2018.
“The effect of this unilateral executive amnesty, among other things, contributed to a surge of minors at the southern border that yielded terrible humanitarian consequences,” Mr. Sessions said during the press conference. “[DACA has] also denied jobs to hundreds of thousands of Americans by allowing those same illegal aliens to take those jobs. To have a lawful system of immigration that serves the national interest, we cannot admit everyone. Therefore the nation must set and enforce a limit on how many immigrants we admit and that means all cannot be accepted.”
In a statement issued shortly after the press conference, President Trump said winding down the DACA program is in the nation’s best interest, and that there can be no principled immigration reform if the executive branch is able to “rewrite or nullify federal laws at will.
“As President, my highest duty is to defend the American people and the Constitution of the United States of America,” President Trump said in the statement. “At the same time, I do not favor punishing children, most of whom are now adults, for the actions of their parents. But we must also recognize that we are nation of opportunity because we are a nation of laws.”
The DACA program was created by the Obama administration in 2012 as a way of protecting young, undocumented immigrants from deportation after Congress repeatedly blocked legislation that would develop such a safe haven. The policy allowed about 800,000 young adults brought to the United States illegally as children to work legally in the U.S. and remain in the country without the fear of deportation.
The program’s end will affect the growing number of medical students with DACA status and likely jeopardize the funding invested in their training. Sixty-two medical schools accept applications from DACA applicants, according to the Association of American Medical Colleges (AAMC). For the 2016 -2017 school year, 113 students with DACA status applied to US medical schools, and there were 65 medical students enrolled who had DACA status. AAMC does not collect data on medical students with DACA status; the National Resident Matching Program, likewise, does not collect data on residents with DACA status.
Loyola University in Chicago is one institute that could be significantly impacted by recension of DACA. The university has accepted more students with DACA status than any other U.S. medical school, and currently has 32 DACA students attending, said Mark Kuczewski, Ph.D., chair of medical education at Loyola University.
“It’s a tragic decision,” he said in an interview. “It once again puts a cloud over these young people who DACA has given the first real opportunity to come out of the shadows, be educated, and serve the community. Now they’re returned back to the situation of uncertainty.”
The decision to end DACA means that current DACA medical students may not be able to finish their training and that those close to completion may not be able to use their degrees in the workforce, Dr. Kuczewski said. Since they are not citizens, DACA students do not qualify for federal student loans, so medical schools must find ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Loyola’s Stritch School of Medicine, Dr. Kuczewski said. However, such loan programs require DACA status. Without DACA or another path to citizenship, medical students in the middle of training will not be able to obtain financial aid to finish their training, he said. The work authorization that DACA provided will also be eliminated.
Dr. Kuczewski said his university plans to advocate strongly for Congress to pass legislation to protect DACA youth, such as the Dream Act of 2017.
“We are going to advocate strongly because we believe this is common sense,” he said. “You don’t just throw away the talents of these young people and the investments they’ve made in their education and the investments we’ve made in them. DACA has given many people the chance to see these young people as students, as employees, as colleagues, and we hope that helps people to mobilize.”
In a statement, Jack Ende, MD, president of the American College of Physicians, said President Trump’s decision to end the DACA program threatens to deny the country the talents of more than half a million individuals making enormous contributions and will also undermine public health and medical education.
“Today’s executive order has the potential to gravely impact public health,” Dr. Ende said in the statement. “We know that noncitizens and undocumented immigrants are more likely to lack health insurance coverage. If the nearly 800,000 people who are currently benefiting from DACA have their protections removed, many will avoid seeking health care in order to reduce the risk of detection and deportation. … Those who seek to serve in the health care professions will be denied that opportunity.”
The Immigration Reform Law Institute praised President Trump’s decision to rescind the DACA program, calling the policy an affront to Congress and a violation of the U.S. Constitution.
“Contrary to former President Obama’s claims, not only is DACA not authorized by federal statute, but prior to the unlawful program, deferred action has only ever been applied to small numbers of illegal aliens on a case-by-case basis,” Dale Wilcox, executive director, said in a statement. “Applying it to approximately 15% of the illegal alien population was never a proper exercise of the president’s discretion under the Constitution and is inconsistent with the president’s duty to take care that the laws be faithfully executed. By rescinding DACA, President Trump has put an end to the previous administration’s flagrant violation of our immigration laws and its abuse of hard-working American taxpayers.”
In a memorandum issued Sept. 5, the Department of Homeland Security said it will begin winding down the DACA program, while providing a limited window in which it will adjudicate certain requests for DACA and associated applications. DHS will adjudicate, on an individual, case-by-case basis, properly filed pending DACA initial requests and associated applications for employment authorization documents that have been accepted by the department as of Sept.5, 2017, according to the memorandum. All DACA initial requests and associated applications filed after this date will be rejected.
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On Twitter @legal_med
President Trump has ended the Obama administration’s Deferred Action for Childhood Arrivals (DACA) program, a policy that protected immigrants who came to the United States as children from deportation and authorized them to work in the United States.
In a Sept. 5 press conference, Attorney General Jeff Sessions called the DACA program an unconstitutional overreach of executive branch power by the former administration that deliberately sought to undermine the legislative branch. Rollback of the DACA program will begin immediately, Mr. Sessions said, with the program expiring completely on March 5, 2018.
“The effect of this unilateral executive amnesty, among other things, contributed to a surge of minors at the southern border that yielded terrible humanitarian consequences,” Mr. Sessions said during the press conference. “[DACA has] also denied jobs to hundreds of thousands of Americans by allowing those same illegal aliens to take those jobs. To have a lawful system of immigration that serves the national interest, we cannot admit everyone. Therefore the nation must set and enforce a limit on how many immigrants we admit and that means all cannot be accepted.”
In a statement issued shortly after the press conference, President Trump said winding down the DACA program is in the nation’s best interest, and that there can be no principled immigration reform if the executive branch is able to “rewrite or nullify federal laws at will.
“As President, my highest duty is to defend the American people and the Constitution of the United States of America,” President Trump said in the statement. “At the same time, I do not favor punishing children, most of whom are now adults, for the actions of their parents. But we must also recognize that we are nation of opportunity because we are a nation of laws.”
The DACA program was created by the Obama administration in 2012 as a way of protecting young, undocumented immigrants from deportation after Congress repeatedly blocked legislation that would develop such a safe haven. The policy allowed about 800,000 young adults brought to the United States illegally as children to work legally in the U.S. and remain in the country without the fear of deportation.
The program’s end will affect the growing number of medical students with DACA status and likely jeopardize the funding invested in their training. Sixty-two medical schools accept applications from DACA applicants, according to the Association of American Medical Colleges (AAMC). For the 2016 -2017 school year, 113 students with DACA status applied to US medical schools, and there were 65 medical students enrolled who had DACA status. AAMC does not collect data on medical students with DACA status; the National Resident Matching Program, likewise, does not collect data on residents with DACA status.
Loyola University in Chicago is one institute that could be significantly impacted by recension of DACA. The university has accepted more students with DACA status than any other U.S. medical school, and currently has 32 DACA students attending, said Mark Kuczewski, Ph.D., chair of medical education at Loyola University.
“It’s a tragic decision,” he said in an interview. “It once again puts a cloud over these young people who DACA has given the first real opportunity to come out of the shadows, be educated, and serve the community. Now they’re returned back to the situation of uncertainty.”
The decision to end DACA means that current DACA medical students may not be able to finish their training and that those close to completion may not be able to use their degrees in the workforce, Dr. Kuczewski said. Since they are not citizens, DACA students do not qualify for federal student loans, so medical schools must find ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Loyola’s Stritch School of Medicine, Dr. Kuczewski said. However, such loan programs require DACA status. Without DACA or another path to citizenship, medical students in the middle of training will not be able to obtain financial aid to finish their training, he said. The work authorization that DACA provided will also be eliminated.
Dr. Kuczewski said his university plans to advocate strongly for Congress to pass legislation to protect DACA youth, such as the Dream Act of 2017.
“We are going to advocate strongly because we believe this is common sense,” he said. “You don’t just throw away the talents of these young people and the investments they’ve made in their education and the investments we’ve made in them. DACA has given many people the chance to see these young people as students, as employees, as colleagues, and we hope that helps people to mobilize.”
In a statement, Jack Ende, MD, president of the American College of Physicians, said President Trump’s decision to end the DACA program threatens to deny the country the talents of more than half a million individuals making enormous contributions and will also undermine public health and medical education.
“Today’s executive order has the potential to gravely impact public health,” Dr. Ende said in the statement. “We know that noncitizens and undocumented immigrants are more likely to lack health insurance coverage. If the nearly 800,000 people who are currently benefiting from DACA have their protections removed, many will avoid seeking health care in order to reduce the risk of detection and deportation. … Those who seek to serve in the health care professions will be denied that opportunity.”
The Immigration Reform Law Institute praised President Trump’s decision to rescind the DACA program, calling the policy an affront to Congress and a violation of the U.S. Constitution.
“Contrary to former President Obama’s claims, not only is DACA not authorized by federal statute, but prior to the unlawful program, deferred action has only ever been applied to small numbers of illegal aliens on a case-by-case basis,” Dale Wilcox, executive director, said in a statement. “Applying it to approximately 15% of the illegal alien population was never a proper exercise of the president’s discretion under the Constitution and is inconsistent with the president’s duty to take care that the laws be faithfully executed. By rescinding DACA, President Trump has put an end to the previous administration’s flagrant violation of our immigration laws and its abuse of hard-working American taxpayers.”
In a memorandum issued Sept. 5, the Department of Homeland Security said it will begin winding down the DACA program, while providing a limited window in which it will adjudicate certain requests for DACA and associated applications. DHS will adjudicate, on an individual, case-by-case basis, properly filed pending DACA initial requests and associated applications for employment authorization documents that have been accepted by the department as of Sept.5, 2017, according to the memorandum. All DACA initial requests and associated applications filed after this date will be rejected.
[email protected]
On Twitter @legal_med
Zika’s 2017 summer less active than 2016
Zika may not have gone away this summer, but it didn’t make a comeback, either.
New cases in pregnant women are still being reported, but the numbers are much lower than a year ago, when the infection was kicking into high gear. For the 2 weeks ending Aug. 22, 106 pregnant women with laboratory evidence of Zika virus infection were reported: 43 in the U.S. states and the District of Columbia, and 63 in the U.S. territories, according to the Centers for Disease Control and Prevention.
The total cases reported for the previous 2-week periods, going back to mid-June, look like this: 102 (June 14-27), 160 (June 28–July 11), 95 (July 12-25), and 103 (July 26–Aug. 8). In the summer of 2016, the 2-week period of Aug. 12-25 produced 375 new reports of Zika-infected pregnant women, the CDC data show.
Zika may not have gone away this summer, but it didn’t make a comeback, either.
New cases in pregnant women are still being reported, but the numbers are much lower than a year ago, when the infection was kicking into high gear. For the 2 weeks ending Aug. 22, 106 pregnant women with laboratory evidence of Zika virus infection were reported: 43 in the U.S. states and the District of Columbia, and 63 in the U.S. territories, according to the Centers for Disease Control and Prevention.
The total cases reported for the previous 2-week periods, going back to mid-June, look like this: 102 (June 14-27), 160 (June 28–July 11), 95 (July 12-25), and 103 (July 26–Aug. 8). In the summer of 2016, the 2-week period of Aug. 12-25 produced 375 new reports of Zika-infected pregnant women, the CDC data show.
Zika may not have gone away this summer, but it didn’t make a comeback, either.
New cases in pregnant women are still being reported, but the numbers are much lower than a year ago, when the infection was kicking into high gear. For the 2 weeks ending Aug. 22, 106 pregnant women with laboratory evidence of Zika virus infection were reported: 43 in the U.S. states and the District of Columbia, and 63 in the U.S. territories, according to the Centers for Disease Control and Prevention.
The total cases reported for the previous 2-week periods, going back to mid-June, look like this: 102 (June 14-27), 160 (June 28–July 11), 95 (July 12-25), and 103 (July 26–Aug. 8). In the summer of 2016, the 2-week period of Aug. 12-25 produced 375 new reports of Zika-infected pregnant women, the CDC data show.
No obvious choice for treating pruritus in PBC patients
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
FROM THE AMERICAN JOURNAL OF MEDICINE
Vaccinate and consider tofacitinib monotherapy to prevent herpes zoster in RA
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
At a symposium during the 2015 annual meeting of the American College of Rheumatology, William Schaffner, MD, highlighted the connection between the seriousness of an infection, and the respect one has for the solution.
Dr. Schaffner said that “if you don’t fear the infection, you won’t value the solution.” Herpes zoster (HZ) should be feared, and the solution – the live zoster vaccine – valued.
Live zoster vaccine (LZV) was approved in 2006 on the basis of a trial involving more than 38,500 adults over age 60 years, which showed a 51% HZ prevention rate (64% protection in the 60-69 year age group) and a two-thirds reduction in postherpetic neuralgia. Complications and disseminated infection were rare.
HZ vaccination should be offered regardless of a history of varicella infection or prior shingles, as HZ may recur.
There is an imperative need to know who is at risk, when and how they should be vaccinated, and what other risk reduction measures should be considered.
John J. Cush, MD, is director of clinical rheumatology at Baylor Scott & White Research Institute and professor of medicine and rheumatology at Baylor University Medical Center, both in Dallas. His comments are taken from his editorial accompanying the two studies by Winthrop et al. (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40188).
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
The results of two studies of tofacitinib treatment for rheumatoid arthritis offer evidence to support the use of the drug without concomitant conventional synthetic disease-modifying antirheumatic drugs in order to reduce the risk of risk of herpes zoster infection and the safety of starting the drug 2-3 weeks after administering live zoster vaccine.
The risk of herpes zoster infection was elevated among rheumatoid arthritis (RA) patients receiving tofacitinib (Xeljanz) with glucocorticoids, compared with those receiving tofacitinib monotherapy, according to an analysis of data from 19 phase 2, phase 3, and long-term extension studies of tofacitinib.
“Further, physicians should continue to consider shingles vaccination prior to starting tofacitinib or biologic therapy,” they wrote.
Dr. Winthrop is the first author of a separate phase 2 study that also appears in Arthritis & Rheumatology, which suggests that live zoster vaccine (LZV) is safe in RA patients who start tofacitinib 2-3 weeks after vaccination. The study also showed that varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses to LZV are similar in tofacitinib- and placebo-treated patients.
“Our study provides the first data with this vaccine in the RA setting and suggests that these patients, even while using nonbiologic DMARDs at the time of vaccination, are capable of mounting adequate immune responses to this vaccine. Further, our data suggest that the use of tofacitinib following VZV vaccination in the RA setting did not impact negatively the vaccine immunogenicity or the time course of the immune response to the vaccine,” he and his colleagues wrote (Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187).
Increased herpes zoster risk in combination therapy
In the first study, herpes zoster (HZ) was reported in 636 of 6,192 patients over a median follow-up of 3 years of tofacitinib exposure, for an incident rate (IR) of 4.0 per 100 patient-years. However, IRs varied by region, ranging from 2.4 in Eastern Europe to 8.0 and 8.4 in Japan and Korea, respectively.
Further, in phase 3 studies, the IRs varied by tofacitinib dose, background use of conventional csDMARDs, and baseline glucocorticoid use; the rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6), and highest in those on tofacitinib at 10 mg twice daily with csDMARDs and glucocorticoids (IR, 5.4), the investigators found.
Independent risk factors for HZ included age, glucocorticoid use, tofacitinib dose, and enrollment within Asia, they said.
“Shingles, or reactivation of varicella virus, is a common and potentially debilitating illness. Around one-third of the general population will develop HZ in their lifetime, and approximately 10% of these patients develop postherpetic neuralgia which can last months to years and cause significant pain and morbidity,” the investigators wrote, adding that RA patients are at 1.5- to 2-fold greater risk vs. similarly aged individuals in the general population.
RA itself and treatment with glucocorticoids are known to increase HZ risk, but recent data have suggested that Janus kinase inhibitors, such as tofacitinib, and tumor necrosis factor antagonists are also associated with a higher rate of HZ. Additionally, a theoretical risk exists with various csDMARDs, they said.
“Given the increased risk of HZ observed among patients with RA versus the general population and the risk associated with RA therapies, it is possible that risk of HZ may be further increased when such therapies are combined,” they wrote.
Indeed, the findings of the study demonstrate an increased risk of HZ with tofacitinib in combination with glucocorticoids vs. tofacitinib monotherapy.
Further research is necessary to understand why Japanese and Korean patients are at elevated risk, and to understand the mechanism for the effects of combination therapy on VZV reactivation, they concluded.
LZV immunogenicity holds up during tofacitinib treatment
In the second study, 112 patients aged 50 years and older with active RA on background methotrexate received LZV and were then randomized to receive 5 mg tofacitinib twice daily or placebo 2-3 weeks after vaccination.
At 6 weeks after vaccination, VZV-specific IgG geometric mean fold rise (GMFR) was 2.11 and 1.74 in the tofacitinib and placebo patients, respectively; at all postvaccination time points at which VZV-specific IgG levels were evaluated, there was a trend toward numerically higher GMFR in tofacitinib patients, but the differences were not statistically significant. Also, the proportion of patients developing a 1.5-fold or greater postvaccination rise in IgG levels at 6 weeks trended higher for tofacitinib (57.4% vs. 43.4% with placebo).
VZV-specific T-cell GMFR at 6 weeks increased similarly in the groups (1.50 with tofacitinib and 1.29 with placebo).
Serious adverse events occurred in three patients in the tofacitinib group (5.5%) and in none of the placebo patients.
“The three SAEs included one case each of cholangitis and bronchitis, and once case of disseminated primary varicella,” the investigators said, noting that the onset of the latter was 16 days postvaccination, 2 days after starting tofacitinib. The rash resolved with discontinuation of tofacitinib and treatment with valacyclovir for 7 days.
The findings suggest that patients with active RA develop robust immune responses to HZ vaccine, and that starting tofacitinib 2-3 weeks after vaccination has no negative impact on the established immune response.
“Importantly, while our results suggest the vaccine is safe for patients with RA with prior VZV exposure, they also indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2-3 weeks before starting immunosuppression with tofacitinib,” they said, noting that the current data suggest 4 weeks might be preferable.
Alternatively, testing patients who don’t recollect a history of chickenpox to ensure prior VZV exposure prior to vaccination could also mitigate the risk, they said.
“Further research is necessary to understand the risk of this complication, as well as the long-term effectiveness of this vaccine to prevent HZ in this high-risk population,” they concluded.
Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: HZ rates were lowest among patients on tofacitinib monotherapy at a dose of 5 mg twice daily (IR, 0.6).
Data source: A phase 2 trial of 112 patients, and a review of 19 studies involving 6,192 patients.
Disclosures: Both studies were sponsored by Pfizer. Dr. Winthrop has received research grants from and served as a scientific consultant to Pfizer. Other authors also reported financial relationships with Pfizer.