Image by Spencer Phillips

BERLIN—New research suggests the investigational gene therapy BMN 270 can allow patients with severe hemophilia A to maintain normal factor VIII (FVIII) levels for over a year.

In a phase 1/2 study, patients who received the highest dose of BMN 270 had median and mean FVIII levels that were consistently within the normal range from week 20 to week 52 and beyond.

The highest dose of BMN 270 reduced the mean annual FVIII infusions by 94% and the mean annualized bleed rate (ABR) by 97%, when compared to prophylaxis.

BMN 270 was also considered well tolerated, and none of the patients developed FVIII inhibitors.

The most common adverse event (AE) in this study was alanine aminotransferase (ALT) elevations. In fact, the increase in ALT levels exceeded a pre-specified threshold, which resulted in the study being placed on hold last year.

However, the hold was ultimately lifted. All cases of ALT increase were non-serious, and all patients with ALT increases have either stopped receiving corticosteroids or are being tapered off of them.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented these results as a late-breaking abstract at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The research was sponsored by BioMarin.

In this phase 1/2 study, 15 patients with severe hemophilia A (FVIII activity levels less than 1%) received a single dose of BMN 270.

Seven patients received a dose of 6e13 vg/kg, 6 received 4e13 vg/kg, and 2 were treated at lower doses as part of dose-escalation and did not achieve therapeutic efficacy.

Safety

Overall, BMN 270 was considered well tolerated across all doses. None of the patients developed inhibitors to FVIII, and none of them withdrew from the study.

The most common AEs across all dose cohorts were ALT elevations (n=10, 67%), arthralgia (n=7, 47%), and back pain, fatigue, and headache (n=5, 33% each).

All ALT increases were non-serious, of limited duration (lasting 0.4 to 7 weeks), and grade 1 in severity. All 7 patients at the 6e13 vg/kg dose remain off of corticosteroids, with no lasting significant impact on FVIII expression and normal ALT levels.

Three of the 6 patients in the 4e13 vg/kg dose cohort received corticosteroids for ALT increases. One has successfully tapered off corticosteroids, and 2 are still tapering off of them.

Two patients reported serious AEs during the study.

One patient was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving BMN 270 (4e13 vg/kg dose). The event resolved within 48 hours following treatment with paracetamol. The event was considered related to BMN 270.

The other serious AE—planned total knee replacement for chronic arthropathy—was not related to BMN 270.

FVIII levels: 6e13 vg/kg

For patients in the 6e13 vg/kg dose cohort, median and mean FVIII levels from week 20 through 52 have been consistently within the normal levels post-treatment. At 1 year after dosing, the median and mean FVIII levels continue to be above 50%.

Table 1:  FVIII levels (%) of 6e13 vg/kg dose patients by visit (n=7)

* Weeks were windowed by +/- 2 weeks

** For week 32, one patient had no FVIII reading

***Bolded numbers are in the normal range of FVIII as defined by the World Federation of Hemophilia

FVIII levels: 4e13 vg/kg

For the 4e13 vg/kg dose cohort, the median and mean FVIII levels from week 8 to 24 are in the mild level. Three of these subjects, who have been observed for 24 weeks, are at the upper end of mild.

Table 2:  FVIII levels (%) of 4e13 vg/kg dose patients* by visit (n=6)

*Weeks were windowed by +/- 2 weeks

** Bolded numbers are in the mild range of FVIII as defined by the World Federation of Hemophilia

ABR and FVIII infusions

Six of the 7 patients in the 6e13 vg/kg cohort were on pre-study prophylaxis.

After these patients received a single dose BMN270 and reached a FVIII level above 5%, the mean ABR was reduced by 97%, from 16.3 to 0.5. The median ABR for these patients was reduced from 16.5 to 0.

The mean annualized FVIII infusions were reduced by 94%, from 136.7 to 8.5. And the median annualized FVIII infusions were reduced from 138.5 to 0.

All 6 patients in the 4e13 vg/kg dose cohort were on pre-study prophylaxis.

The mean ABR was reduced from 12.2 pre-study to 0 after they reached an FVIII level above 5%. The median ABR for these patients was reduced from 8.0 to 0.

The mean annualized FVIII infusions were reduced from 144.2 to 0. The median annualized FVIII infusions were reduced from 155.5 to 0.

“Patients at the 2 highest doses have stopped prophylactic treatment and, to date, bleeds have effectively been eliminated,” Dr Pasi noted.

Based on these results, BioMarin is planning a phase 3 registrational study of BMN 270. The study will likely include fewer than 100 patients and collect data for no longer than a year after a single dose of BMN 270, with subsequent long-term follow-up.

The company is moving the 6e13 vg/kg dose forward but will consider doing an additional study with the 4e13 vg/kg dose at a later date. 

Image by Spencer Phillips

BERLIN—New research suggests the investigational gene therapy BMN 270 can allow patients with severe hemophilia A to maintain normal factor VIII (FVIII) levels for over a year.

In a phase 1/2 study, patients who received the highest dose of BMN 270 had median and mean FVIII levels that were consistently within the normal range from week 20 to week 52 and beyond.

The highest dose of BMN 270 reduced the mean annual FVIII infusions by 94% and the mean annualized bleed rate (ABR) by 97%, when compared to prophylaxis.

BMN 270 was also considered well tolerated, and none of the patients developed FVIII inhibitors.

The most common adverse event (AE) in this study was alanine aminotransferase (ALT) elevations. In fact, the increase in ALT levels exceeded a pre-specified threshold, which resulted in the study being placed on hold last year.

However, the hold was ultimately lifted. All cases of ALT increase were non-serious, and all patients with ALT increases have either stopped receiving corticosteroids or are being tapered off of them.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented these results as a late-breaking abstract at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The research was sponsored by BioMarin.

In this phase 1/2 study, 15 patients with severe hemophilia A (FVIII activity levels less than 1%) received a single dose of BMN 270.

Seven patients received a dose of 6e13 vg/kg, 6 received 4e13 vg/kg, and 2 were treated at lower doses as part of dose-escalation and did not achieve therapeutic efficacy.

Safety

Overall, BMN 270 was considered well tolerated across all doses. None of the patients developed inhibitors to FVIII, and none of them withdrew from the study.

The most common AEs across all dose cohorts were ALT elevations (n=10, 67%), arthralgia (n=7, 47%), and back pain, fatigue, and headache (n=5, 33% each).

All ALT increases were non-serious, of limited duration (lasting 0.4 to 7 weeks), and grade 1 in severity. All 7 patients at the 6e13 vg/kg dose remain off of corticosteroids, with no lasting significant impact on FVIII expression and normal ALT levels.

Three of the 6 patients in the 4e13 vg/kg dose cohort received corticosteroids for ALT increases. One has successfully tapered off corticosteroids, and 2 are still tapering off of them.

Two patients reported serious AEs during the study.

One patient was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving BMN 270 (4e13 vg/kg dose). The event resolved within 48 hours following treatment with paracetamol. The event was considered related to BMN 270.

The other serious AE—planned total knee replacement for chronic arthropathy—was not related to BMN 270.

FVIII levels: 6e13 vg/kg

For patients in the 6e13 vg/kg dose cohort, median and mean FVIII levels from week 20 through 52 have been consistently within the normal levels post-treatment. At 1 year after dosing, the median and mean FVIII levels continue to be above 50%.

Table 1:  FVIII levels (%) of 6e13 vg/kg dose patients by visit (n=7)

* Weeks were windowed by +/- 2 weeks

** For week 32, one patient had no FVIII reading

***Bolded numbers are in the normal range of FVIII as defined by the World Federation of Hemophilia

FVIII levels: 4e13 vg/kg

For the 4e13 vg/kg dose cohort, the median and mean FVIII levels from week 8 to 24 are in the mild level. Three of these subjects, who have been observed for 24 weeks, are at the upper end of mild.

Table 2:  FVIII levels (%) of 4e13 vg/kg dose patients* by visit (n=6)

*Weeks were windowed by +/- 2 weeks

** Bolded numbers are in the mild range of FVIII as defined by the World Federation of Hemophilia

ABR and FVIII infusions

Six of the 7 patients in the 6e13 vg/kg cohort were on pre-study prophylaxis.

After these patients received a single dose BMN270 and reached a FVIII level above 5%, the mean ABR was reduced by 97%, from 16.3 to 0.5. The median ABR for these patients was reduced from 16.5 to 0.

The mean annualized FVIII infusions were reduced by 94%, from 136.7 to 8.5. And the median annualized FVIII infusions were reduced from 138.5 to 0.

All 6 patients in the 4e13 vg/kg dose cohort were on pre-study prophylaxis.

The mean ABR was reduced from 12.2 pre-study to 0 after they reached an FVIII level above 5%. The median ABR for these patients was reduced from 8.0 to 0.

The mean annualized FVIII infusions were reduced from 144.2 to 0. The median annualized FVIII infusions were reduced from 155.5 to 0.

“Patients at the 2 highest doses have stopped prophylactic treatment and, to date, bleeds have effectively been eliminated,” Dr Pasi noted.

Based on these results, BioMarin is planning a phase 3 registrational study of BMN 270. The study will likely include fewer than 100 patients and collect data for no longer than a year after a single dose of BMN 270, with subsequent long-term follow-up.

The company is moving the 6e13 vg/kg dose forward but will consider doing an additional study with the 4e13 vg/kg dose at a later date. 

Image by Spencer Phillips

BERLIN—New research suggests the investigational gene therapy BMN 270 can allow patients with severe hemophilia A to maintain normal factor VIII (FVIII) levels for over a year.

In a phase 1/2 study, patients who received the highest dose of BMN 270 had median and mean FVIII levels that were consistently within the normal range from week 20 to week 52 and beyond.

The highest dose of BMN 270 reduced the mean annual FVIII infusions by 94% and the mean annualized bleed rate (ABR) by 97%, when compared to prophylaxis.

BMN 270 was also considered well tolerated, and none of the patients developed FVIII inhibitors.

The most common adverse event (AE) in this study was alanine aminotransferase (ALT) elevations. In fact, the increase in ALT levels exceeded a pre-specified threshold, which resulted in the study being placed on hold last year.

However, the hold was ultimately lifted. All cases of ALT increase were non-serious, and all patients with ALT increases have either stopped receiving corticosteroids or are being tapered off of them.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, presented these results as a late-breaking abstract at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress. The research was sponsored by BioMarin.

In this phase 1/2 study, 15 patients with severe hemophilia A (FVIII activity levels less than 1%) received a single dose of BMN 270.

Seven patients received a dose of 6e13 vg/kg, 6 received 4e13 vg/kg, and 2 were treated at lower doses as part of dose-escalation and did not achieve therapeutic efficacy.

Safety

Overall, BMN 270 was considered well tolerated across all doses. None of the patients developed inhibitors to FVIII, and none of them withdrew from the study.

The most common AEs across all dose cohorts were ALT elevations (n=10, 67%), arthralgia (n=7, 47%), and back pain, fatigue, and headache (n=5, 33% each).

All ALT increases were non-serious, of limited duration (lasting 0.4 to 7 weeks), and grade 1 in severity. All 7 patients at the 6e13 vg/kg dose remain off of corticosteroids, with no lasting significant impact on FVIII expression and normal ALT levels.

Three of the 6 patients in the 4e13 vg/kg dose cohort received corticosteroids for ALT increases. One has successfully tapered off corticosteroids, and 2 are still tapering off of them.

Two patients reported serious AEs during the study.

One patient was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving BMN 270 (4e13 vg/kg dose). The event resolved within 48 hours following treatment with paracetamol. The event was considered related to BMN 270.

The other serious AE—planned total knee replacement for chronic arthropathy—was not related to BMN 270.

FVIII levels: 6e13 vg/kg

For patients in the 6e13 vg/kg dose cohort, median and mean FVIII levels from week 20 through 52 have been consistently within the normal levels post-treatment. At 1 year after dosing, the median and mean FVIII levels continue to be above 50%.

Table 1:  FVIII levels (%) of 6e13 vg/kg dose patients by visit (n=7)

* Weeks were windowed by +/- 2 weeks

** For week 32, one patient had no FVIII reading

***Bolded numbers are in the normal range of FVIII as defined by the World Federation of Hemophilia

FVIII levels: 4e13 vg/kg

For the 4e13 vg/kg dose cohort, the median and mean FVIII levels from week 8 to 24 are in the mild level. Three of these subjects, who have been observed for 24 weeks, are at the upper end of mild.

Table 2:  FVIII levels (%) of 4e13 vg/kg dose patients* by visit (n=6)

*Weeks were windowed by +/- 2 weeks

** Bolded numbers are in the mild range of FVIII as defined by the World Federation of Hemophilia

ABR and FVIII infusions

Six of the 7 patients in the 6e13 vg/kg cohort were on pre-study prophylaxis.

After these patients received a single dose BMN270 and reached a FVIII level above 5%, the mean ABR was reduced by 97%, from 16.3 to 0.5. The median ABR for these patients was reduced from 16.5 to 0.

The mean annualized FVIII infusions were reduced by 94%, from 136.7 to 8.5. And the median annualized FVIII infusions were reduced from 138.5 to 0.

All 6 patients in the 4e13 vg/kg dose cohort were on pre-study prophylaxis.

The mean ABR was reduced from 12.2 pre-study to 0 after they reached an FVIII level above 5%. The median ABR for these patients was reduced from 8.0 to 0.

The mean annualized FVIII infusions were reduced from 144.2 to 0. The median annualized FVIII infusions were reduced from 155.5 to 0.

“Patients at the 2 highest doses have stopped prophylactic treatment and, to date, bleeds have effectively been eliminated,” Dr Pasi noted.

Based on these results, BioMarin is planning a phase 3 registrational study of BMN 270. The study will likely include fewer than 100 patients and collect data for no longer than a year after a single dose of BMN 270, with subsequent long-term follow-up.

The company is moving the 6e13 vg/kg dose forward but will consider doing an additional study with the 4e13 vg/kg dose at a later date. 

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Photo by Patrick Pelletier

MADRID—Results of the DESTINY trial suggest that chronic myeloid leukemia (CML) patients may improve their chances of successfully stopping treatment with tyrosine kinase inhibitors (TKIs) by first reducing the dose they receive.

CML patients in deep molecular response (MR4) at study entry had a low rate of recurrence when they first de-escalated their TKI dose—receiving half the standard dose—for a year and then completely stopped receiving TKI treatment for a year.

The 2-year recurrence-free survival (RFS) rate was 77%, which is better than the RFS in any comparable study to date, according to Richard Clark, MD, of the University of Liverpool in Liverpool, UK, and his colleagues.

Dr Clark presented results from DESTINY at the 22nd Congress of the European Hematology Association (EHA) as abstract S423.

DESTINY included 174 CML patients (98 male, 76 female) in stable major molecular response (MMR).

At study entry, patients had received imatinib (n=148), nilotinib (n=16), or dasatinib (n=10) for a median duration of 6.8 years.

For the first 12 months of the study, patients had their TKI dose reduced to half the standard dose. So they received imatinib at 200 mg daily, dasatinib at 50 mg daily, or nilotinib at 200 mg twice daily. After that, patients stopped treatment completely.

After the first 12 months, molecular recurrence was lower in patients with stable MR4 at study entry than in patients who were not in MR4 (but still in MMR)—2.4% (3/125) and 18.4% (9/49), respectively (P<0.001).

During the following 12 months, in which patients had completely stopped TKI treatment, there were 26 recurrences and 4 withdrawals among the remaining 117 patients who were in MR4 at baseline, as well as 20 recurrences and 4 withdrawals among the 36 patients not in MR4.

So the RFS was 77% among patients in MR4 at baseline and 39% among the patients not in MR4 (P<0.001).

The researchers said the probability of RFS was unrelated to patients’ age, gender, performance status, or the prior TKI they received (imatinib vs second-generation TKI).

All patients with recurrence ultimately returned to deep remissions when they resumed their TKI treatment.

“TKI de-escalation is safe for most CML patients with stable and excellent responses to TKI therapy after some years of treatment and is associated with improvement in symptoms,” Dr Clark said.

“Overall, our findings are better than any other studies worldwide and imply that our unique, gradual withdrawal of treatment might be important. We don’t yet understand why our results are so good, but this is a happy problem to have.”

Photo by Patrick Pelletier

MADRID—Results of the DESTINY trial suggest that chronic myeloid leukemia (CML) patients may improve their chances of successfully stopping treatment with tyrosine kinase inhibitors (TKIs) by first reducing the dose they receive.

CML patients in deep molecular response (MR4) at study entry had a low rate of recurrence when they first de-escalated their TKI dose—receiving half the standard dose—for a year and then completely stopped receiving TKI treatment for a year.

The 2-year recurrence-free survival (RFS) rate was 77%, which is better than the RFS in any comparable study to date, according to Richard Clark, MD, of the University of Liverpool in Liverpool, UK, and his colleagues.

Dr Clark presented results from DESTINY at the 22nd Congress of the European Hematology Association (EHA) as abstract S423.

DESTINY included 174 CML patients (98 male, 76 female) in stable major molecular response (MMR).

At study entry, patients had received imatinib (n=148), nilotinib (n=16), or dasatinib (n=10) for a median duration of 6.8 years.

For the first 12 months of the study, patients had their TKI dose reduced to half the standard dose. So they received imatinib at 200 mg daily, dasatinib at 50 mg daily, or nilotinib at 200 mg twice daily. After that, patients stopped treatment completely.

After the first 12 months, molecular recurrence was lower in patients with stable MR4 at study entry than in patients who were not in MR4 (but still in MMR)—2.4% (3/125) and 18.4% (9/49), respectively (P<0.001).

During the following 12 months, in which patients had completely stopped TKI treatment, there were 26 recurrences and 4 withdrawals among the remaining 117 patients who were in MR4 at baseline, as well as 20 recurrences and 4 withdrawals among the 36 patients not in MR4.

So the RFS was 77% among patients in MR4 at baseline and 39% among the patients not in MR4 (P<0.001).

The researchers said the probability of RFS was unrelated to patients’ age, gender, performance status, or the prior TKI they received (imatinib vs second-generation TKI).

All patients with recurrence ultimately returned to deep remissions when they resumed their TKI treatment.

“TKI de-escalation is safe for most CML patients with stable and excellent responses to TKI therapy after some years of treatment and is associated with improvement in symptoms,” Dr Clark said.

“Overall, our findings are better than any other studies worldwide and imply that our unique, gradual withdrawal of treatment might be important. We don’t yet understand why our results are so good, but this is a happy problem to have.”

Photo by Patrick Pelletier

MADRID—Results of the DESTINY trial suggest that chronic myeloid leukemia (CML) patients may improve their chances of successfully stopping treatment with tyrosine kinase inhibitors (TKIs) by first reducing the dose they receive.

CML patients in deep molecular response (MR4) at study entry had a low rate of recurrence when they first de-escalated their TKI dose—receiving half the standard dose—for a year and then completely stopped receiving TKI treatment for a year.

The 2-year recurrence-free survival (RFS) rate was 77%, which is better than the RFS in any comparable study to date, according to Richard Clark, MD, of the University of Liverpool in Liverpool, UK, and his colleagues.

Dr Clark presented results from DESTINY at the 22nd Congress of the European Hematology Association (EHA) as abstract S423.

DESTINY included 174 CML patients (98 male, 76 female) in stable major molecular response (MMR).

At study entry, patients had received imatinib (n=148), nilotinib (n=16), or dasatinib (n=10) for a median duration of 6.8 years.

For the first 12 months of the study, patients had their TKI dose reduced to half the standard dose. So they received imatinib at 200 mg daily, dasatinib at 50 mg daily, or nilotinib at 200 mg twice daily. After that, patients stopped treatment completely.

After the first 12 months, molecular recurrence was lower in patients with stable MR4 at study entry than in patients who were not in MR4 (but still in MMR)—2.4% (3/125) and 18.4% (9/49), respectively (P<0.001).

During the following 12 months, in which patients had completely stopped TKI treatment, there were 26 recurrences and 4 withdrawals among the remaining 117 patients who were in MR4 at baseline, as well as 20 recurrences and 4 withdrawals among the 36 patients not in MR4.

So the RFS was 77% among patients in MR4 at baseline and 39% among the patients not in MR4 (P<0.001).

The researchers said the probability of RFS was unrelated to patients’ age, gender, performance status, or the prior TKI they received (imatinib vs second-generation TKI).

All patients with recurrence ultimately returned to deep remissions when they resumed their TKI treatment.

“TKI de-escalation is safe for most CML patients with stable and excellent responses to TKI therapy after some years of treatment and is associated with improvement in symptoms,” Dr Clark said.

“Overall, our findings are better than any other studies worldwide and imply that our unique, gradual withdrawal of treatment might be important. We don’t yet understand why our results are so good, but this is a happy problem to have.”

Guselkumab, a monoclonal antibody that targets interleukin (IL)-23, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.

The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.

emechcatie@frontlinemedcom.com

Guselkumab, a monoclonal antibody that targets interleukin (IL)-23, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.

The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.

emechcatie@frontlinemedcom.com

Guselkumab, a monoclonal antibody that targets interleukin (IL)-23, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.

The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.

emechcatie@frontlinemedcom.com

A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”

“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”

The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.

“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.

“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.

The committee also recommended that the FDA:

• Incorporate public health considerations into opioid-related regulatory decisions.
• Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
• Ensure that public health considerations are adequately incorporated into clinical development.
• Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.

“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”

The committee also recommended strengthening the postapproval oversight of opioids.

A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.

“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”

Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:

• Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
• Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
• Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
• Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.

According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”

Indeed, things will get worse before they get better, the committee predicted.

“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”

sworcester@frontlinemedcom.com

A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”

“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”

The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.

“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.

“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.

The committee also recommended that the FDA:

• Incorporate public health considerations into opioid-related regulatory decisions.
• Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
• Ensure that public health considerations are adequately incorporated into clinical development.
• Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.

“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”

The committee also recommended strengthening the postapproval oversight of opioids.

A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.

“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”

Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:

• Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
• Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
• Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
• Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.

According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”

Indeed, things will get worse before they get better, the committee predicted.

“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”

sworcester@frontlinemedcom.com

A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”

“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”

The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.

“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.

“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.

The committee also recommended that the FDA:

• Incorporate public health considerations into opioid-related regulatory decisions.
• Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
• Ensure that public health considerations are adequately incorporated into clinical development.
• Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.

“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”

The committee also recommended strengthening the postapproval oversight of opioids.

A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.

“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”

Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:

• Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
• Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
• Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
• Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.

According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”

Indeed, things will get worse before they get better, the committee predicted.

“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”

sworcester@frontlinemedcom.com

Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).

I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).

I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).

I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

Senate Republican leadership released its update to the Better Care Reconciliation Act, but the jury is still out on whether this version will be able to garner the support of 50 Republicans in the upper chamber of Congress.

The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.

sndr/istockphoto.com

gtwachtman@frontlinemedcom.com

Senate Republican leadership released its update to the Better Care Reconciliation Act, but the jury is still out on whether this version will be able to garner the support of 50 Republicans in the upper chamber of Congress.

The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.

sndr/istockphoto.com

gtwachtman@frontlinemedcom.com

Senate Republican leadership released its update to the Better Care Reconciliation Act, but the jury is still out on whether this version will be able to garner the support of 50 Republicans in the upper chamber of Congress.

The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.

sndr/istockphoto.com

gtwachtman@frontlinemedcom.com

MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.

The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.

Sara Freeman/Frontline Medical News

rhnews@frontlinemedcom.com

On Twitter @rheumnews1

MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.

The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.

Sara Freeman/Frontline Medical News

rhnews@frontlinemedcom.com

On Twitter @rheumnews1

MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.

The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.

Sara Freeman/Frontline Medical News

rhnews@frontlinemedcom.com

On Twitter @rheumnews1

Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock

mkalaycio@frontlinemedcom.com

Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock

mkalaycio@frontlinemedcom.com

Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock

mkalaycio@frontlinemedcom.com

PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.

Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA₂DS₂-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
 

“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.

Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA₂DS₂-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
 

“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.

Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA₂DS₂-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
 

“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com