Ocrelizumab is associated with lower rates of disease activity and progression in patients with relapsing-remitting multiple sclerosis (MS), compared with interferon beta-1a, according to research published in the New England Journal of Medicine. A separate study published in the same journal indicates that ocrelizumab is associated with lower rates of clinical and MRI progression in patients with primary progressive MS, compared with placebo. Ocrelizumab selectively depletes CD20+ B cells, and both studies provide evidence that B cells contribute to the pathogenesis of MS.

“This is the first drug to show a significant effect in slowing disability progression in a phase III trial in primary progressive MS, and therefore the trial represents a landmark study in the field,” said Peter A. Calabresi, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore, in an accompanying editorial. The articles and editorial were published online ahead of print December 21, 2016.

Ocrelizumab in Relapsing-Remitting MS

Stephen L. Hauser, MD, Chair of Neurology at the University of California, San Francisco School of Medicine, and colleagues conducted OPERA I and OPERA II, two phase III studies to investigate the safety and efficacy of ocrelizumab, compared with interferon beta-1a, in patients with relapsing-remitting MS. The trials had identical protocols, but were conducted at separate trial sites. Eligible participants were between ages 18 and 55, had an Expanded Disability Status Scale (EDSS) score no greater than 5.5 at screening, a history of relapses, and MRI abnormalities consistent with MS. Patients who previously had received a B-cell-targeted therapy or other immunosuppressive medication were excluded.

A total of 821 patients in OPERA I and 835 patients in OPERA II were randomized to 600 mg of IV ocrelizumab every 24 weeks or to 44 µg of subcutaneous interferon beta-1a three times weekly. The treatment period was 96 weeks. Each trial site had separate treating and examining investigators, all of whom were unaware of participants’ treatment assignments. The primary end point was the annualized relapse rate by 96 weeks. Secondary end points included the proportion of patients with disability progression confirmed at 12 weeks, the mean number of gadolinium-enhancing lesions identified on T1-weighted MRI, and the proportion of patients with disability improvement confirmed at 12 weeks.

The annualized relapse rate at 96 weeks in OPERA I was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. In OPERA II, the annualized relapse rate was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. These data suggest a 46% lower annualized relapse rate with ocrelizumab in OPERA I and a 47% lower rate with ocrelizumab in OPERA II.

The mean numbers of gadolinium-enhancing lesions in OPERA I were 0.02 with ocrelizumab versus 0.29 with interferon beta-1a. The numbers in OPERA II were 0.02 with ocrelizumab versus 0.42 with interferon beta-1a. The mean numbers of new or newly enlarged T2 hyperintense lesions in OPERA I were 0.32 with ocrelizumab and 1.41 with interferon beta-1a (ie, 77% fewer lesions with ocrelizumab). The values in OPERA II were 0.33 with ocrelizumab versus 1.90 with interferon beta-1a.

In a pooled analysis, 9.1% of patients in the ocrelizumab group had disability progression confirmed at 12 weeks, compared with 13.6% of patients in the interferon beta-1a group. The percentage of patients with disability improvement confirmed at 12 weeks was 20.7% in the ocrelizumab group, compared with 15.6% in the interferon beta-1a group (ie, a 33% higher rate of improvement with ocrelizumab). The effect of ocrelizumab on the rate of confirmed disability improvement was significant in OPERA I, but nonsignificant in OPERA II.

“Additional and extended studies will be required to determine whether the outcomes observed in these 96-week trials, including a near-complete cessation of new plaque formation, as assessed by MRI of the brain, translate into enhanced protection against accrual of disability over the long term,” said Dr. Hauser.

Ocrelizumab in Progressive MS

To examine the safety and efficacy of ocrelizumab in primary progressive MS, Xavier Montalban, MD, PhD, Chair of the Department of Neurology-Neuroimmunology and Director of the MS Centre of Catalonia at the Vall d’Hebron University Hospital in Barcelona, and colleagues conducted the phase III ORATORIO trial. Eligible patients were between ages 18 and 55 and had an EDSS score between 3.0 and 6.5 at screening. Patients with a history of relapsing-remitting MS, secondary progressive MS, or progressive relapsing MS were excluded, as were patients who had had previous treatment with B-cell-targeted therapies and other immunosuppressive medications.

Patients were randomized in a 2:1 ratio to receive 600 mg of IV ocrelizumab or matching placebo every 24 weeks. Double-blinded treatment was administered for at least 120 weeks. As in the OPERA trials, each trial site had separate treating and examining investigators. Patients who completed the blinded treatment phase were eligible to enter an open-label extension phase.

The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. Secondary end points included the percentage of patients with disability progression confirmed at 24 weeks, change in performance on the timed 25-foot walk from baseline to week 120, change in the total volume of brain lesions on T2-weighted MRI from baseline to week 120, change in brain volume from week 24 to week 120, and change in the Physical Component Summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), version 2, from baseline to week 120.

In all, 488 patients received ocrelizumab, and 244 received placebo. A total of 402 patients in the ocrelizumab arm and 174 controls completed the 120-week treatment period. The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo. The data suggest a 24% reduction in the risk of this outcome with ocrelizumab.

The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab and 35.7% with placebo (ie, a relative risk reduction of 25% with ocrelizumab). The mean change from baseline to week 120 in performance on the timed 25-foot walk was 38.9% with ocrelizumab versus 55.1% with placebo (ie, a relative reduction of 29.3% with ocrelizumab). The researchers found no significant between-group difference in the change in the SF-36 Physical Component Summary score from baseline to week 120.

In addition, the total volume of hyperintense lesions on T2-weighted images from baseline to week 120 decreased with ocrelizumab and increased with placebo (mean percent change, −3.4% vs 7.4%). The adjusted mean percent change in brain volume from week 24 to week 120 was lower with ocrelizumab than with placebo (–0.90% vs –1.09%).

Infusion-related reactions were more common in the ocrelizumab group than among controls. Neoplasms were reported in 11 of 486 patients (2.3%) in the ocrelizumab group and in two of 239 patients (0.8%) in the placebo group. “Safety will continue to be assessed throughout the open-label extension phase,” said Dr. Montalban.

Unknown Mechanism of Action

The mechanism by which B-cell depletion slows disability progression is not fully understood. It “may be multifunctional, because B cells have important roles in antibody secretion, antigen presentation, and the release of effector cytokines,” said Dr. Calabresi. By virtue of their number, B cells may be more important than other antigen-presenting cells in MS.

One potential reason that ocrelizumab showed positive effects in ORATORIO is that the patient population was relatively young (mean age, 45) and had active MRI scans (more than 25% of the population had gadolinium-enhancing lesions). These factors enabled the demonstration of a measurable anti-inflammatory effect of ocrelizumab in patients with inflammation at an early, reversible stage of the disease. “Another possible explanation is that B cells may mediate pathologic processes by secretion of cytokines or by deposition of immunoglobulins after they enter the CNS,” said Dr. Calabresi. “B cells and plasma cells secrete antibodies that may target CNS antigens such as myelin, neurons, and glia, which could accelerate neurodegeneration or inhibit myelin repair. The continued separation of disability progression curves in the ORATORIO trial beyond 52 weeks, when anti-inflammatory effects have been maximized, and success in the relatively noninflammatory disorder of primary progressive MS suggest that additional mechanisms of action may be operational, and further study is warranted.”

Because ocrelizumab appears to entail a higher risk of herpes reactivation and of neoplasms, “clinicians are urged to carefully consider which patients might benefit the most from ocrelizumab and to stay vigilant with regard to monitoring for side effects that could be managed effectively if detected early,” Dr. Calabresi concluded.

—Erik Greb

Suggested Reading

Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Calabresi PA. B-cell depletion - a frontier in monoclonal antibodies for multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Ocrelizumab is associated with lower rates of disease activity and progression in patients with relapsing-remitting multiple sclerosis (MS), compared with interferon beta-1a, according to research published in the New England Journal of Medicine. A separate study published in the same journal indicates that ocrelizumab is associated with lower rates of clinical and MRI progression in patients with primary progressive MS, compared with placebo. Ocrelizumab selectively depletes CD20+ B cells, and both studies provide evidence that B cells contribute to the pathogenesis of MS.

“This is the first drug to show a significant effect in slowing disability progression in a phase III trial in primary progressive MS, and therefore the trial represents a landmark study in the field,” said Peter A. Calabresi, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore, in an accompanying editorial. The articles and editorial were published online ahead of print December 21, 2016.

Ocrelizumab in Relapsing-Remitting MS

Stephen L. Hauser, MD, Chair of Neurology at the University of California, San Francisco School of Medicine, and colleagues conducted OPERA I and OPERA II, two phase III studies to investigate the safety and efficacy of ocrelizumab, compared with interferon beta-1a, in patients with relapsing-remitting MS. The trials had identical protocols, but were conducted at separate trial sites. Eligible participants were between ages 18 and 55, had an Expanded Disability Status Scale (EDSS) score no greater than 5.5 at screening, a history of relapses, and MRI abnormalities consistent with MS. Patients who previously had received a B-cell-targeted therapy or other immunosuppressive medication were excluded.

A total of 821 patients in OPERA I and 835 patients in OPERA II were randomized to 600 mg of IV ocrelizumab every 24 weeks or to 44 µg of subcutaneous interferon beta-1a three times weekly. The treatment period was 96 weeks. Each trial site had separate treating and examining investigators, all of whom were unaware of participants’ treatment assignments. The primary end point was the annualized relapse rate by 96 weeks. Secondary end points included the proportion of patients with disability progression confirmed at 12 weeks, the mean number of gadolinium-enhancing lesions identified on T1-weighted MRI, and the proportion of patients with disability improvement confirmed at 12 weeks.

The annualized relapse rate at 96 weeks in OPERA I was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. In OPERA II, the annualized relapse rate was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. These data suggest a 46% lower annualized relapse rate with ocrelizumab in OPERA I and a 47% lower rate with ocrelizumab in OPERA II.

The mean numbers of gadolinium-enhancing lesions in OPERA I were 0.02 with ocrelizumab versus 0.29 with interferon beta-1a. The numbers in OPERA II were 0.02 with ocrelizumab versus 0.42 with interferon beta-1a. The mean numbers of new or newly enlarged T2 hyperintense lesions in OPERA I were 0.32 with ocrelizumab and 1.41 with interferon beta-1a (ie, 77% fewer lesions with ocrelizumab). The values in OPERA II were 0.33 with ocrelizumab versus 1.90 with interferon beta-1a.

In a pooled analysis, 9.1% of patients in the ocrelizumab group had disability progression confirmed at 12 weeks, compared with 13.6% of patients in the interferon beta-1a group. The percentage of patients with disability improvement confirmed at 12 weeks was 20.7% in the ocrelizumab group, compared with 15.6% in the interferon beta-1a group (ie, a 33% higher rate of improvement with ocrelizumab). The effect of ocrelizumab on the rate of confirmed disability improvement was significant in OPERA I, but nonsignificant in OPERA II.

“Additional and extended studies will be required to determine whether the outcomes observed in these 96-week trials, including a near-complete cessation of new plaque formation, as assessed by MRI of the brain, translate into enhanced protection against accrual of disability over the long term,” said Dr. Hauser.

Ocrelizumab in Progressive MS

To examine the safety and efficacy of ocrelizumab in primary progressive MS, Xavier Montalban, MD, PhD, Chair of the Department of Neurology-Neuroimmunology and Director of the MS Centre of Catalonia at the Vall d’Hebron University Hospital in Barcelona, and colleagues conducted the phase III ORATORIO trial. Eligible patients were between ages 18 and 55 and had an EDSS score between 3.0 and 6.5 at screening. Patients with a history of relapsing-remitting MS, secondary progressive MS, or progressive relapsing MS were excluded, as were patients who had had previous treatment with B-cell-targeted therapies and other immunosuppressive medications.

Patients were randomized in a 2:1 ratio to receive 600 mg of IV ocrelizumab or matching placebo every 24 weeks. Double-blinded treatment was administered for at least 120 weeks. As in the OPERA trials, each trial site had separate treating and examining investigators. Patients who completed the blinded treatment phase were eligible to enter an open-label extension phase.

The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. Secondary end points included the percentage of patients with disability progression confirmed at 24 weeks, change in performance on the timed 25-foot walk from baseline to week 120, change in the total volume of brain lesions on T2-weighted MRI from baseline to week 120, change in brain volume from week 24 to week 120, and change in the Physical Component Summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), version 2, from baseline to week 120.

In all, 488 patients received ocrelizumab, and 244 received placebo. A total of 402 patients in the ocrelizumab arm and 174 controls completed the 120-week treatment period. The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo. The data suggest a 24% reduction in the risk of this outcome with ocrelizumab.

The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab and 35.7% with placebo (ie, a relative risk reduction of 25% with ocrelizumab). The mean change from baseline to week 120 in performance on the timed 25-foot walk was 38.9% with ocrelizumab versus 55.1% with placebo (ie, a relative reduction of 29.3% with ocrelizumab). The researchers found no significant between-group difference in the change in the SF-36 Physical Component Summary score from baseline to week 120.

In addition, the total volume of hyperintense lesions on T2-weighted images from baseline to week 120 decreased with ocrelizumab and increased with placebo (mean percent change, −3.4% vs 7.4%). The adjusted mean percent change in brain volume from week 24 to week 120 was lower with ocrelizumab than with placebo (–0.90% vs –1.09%).

Infusion-related reactions were more common in the ocrelizumab group than among controls. Neoplasms were reported in 11 of 486 patients (2.3%) in the ocrelizumab group and in two of 239 patients (0.8%) in the placebo group. “Safety will continue to be assessed throughout the open-label extension phase,” said Dr. Montalban.

Unknown Mechanism of Action

The mechanism by which B-cell depletion slows disability progression is not fully understood. It “may be multifunctional, because B cells have important roles in antibody secretion, antigen presentation, and the release of effector cytokines,” said Dr. Calabresi. By virtue of their number, B cells may be more important than other antigen-presenting cells in MS.

One potential reason that ocrelizumab showed positive effects in ORATORIO is that the patient population was relatively young (mean age, 45) and had active MRI scans (more than 25% of the population had gadolinium-enhancing lesions). These factors enabled the demonstration of a measurable anti-inflammatory effect of ocrelizumab in patients with inflammation at an early, reversible stage of the disease. “Another possible explanation is that B cells may mediate pathologic processes by secretion of cytokines or by deposition of immunoglobulins after they enter the CNS,” said Dr. Calabresi. “B cells and plasma cells secrete antibodies that may target CNS antigens such as myelin, neurons, and glia, which could accelerate neurodegeneration or inhibit myelin repair. The continued separation of disability progression curves in the ORATORIO trial beyond 52 weeks, when anti-inflammatory effects have been maximized, and success in the relatively noninflammatory disorder of primary progressive MS suggest that additional mechanisms of action may be operational, and further study is warranted.”

Because ocrelizumab appears to entail a higher risk of herpes reactivation and of neoplasms, “clinicians are urged to carefully consider which patients might benefit the most from ocrelizumab and to stay vigilant with regard to monitoring for side effects that could be managed effectively if detected early,” Dr. Calabresi concluded.

—Erik Greb

Suggested Reading

Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Calabresi PA. B-cell depletion - a frontier in monoclonal antibodies for multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Ocrelizumab is associated with lower rates of disease activity and progression in patients with relapsing-remitting multiple sclerosis (MS), compared with interferon beta-1a, according to research published in the New England Journal of Medicine. A separate study published in the same journal indicates that ocrelizumab is associated with lower rates of clinical and MRI progression in patients with primary progressive MS, compared with placebo. Ocrelizumab selectively depletes CD20+ B cells, and both studies provide evidence that B cells contribute to the pathogenesis of MS.

“This is the first drug to show a significant effect in slowing disability progression in a phase III trial in primary progressive MS, and therefore the trial represents a landmark study in the field,” said Peter A. Calabresi, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore, in an accompanying editorial. The articles and editorial were published online ahead of print December 21, 2016.

Ocrelizumab in Relapsing-Remitting MS

Stephen L. Hauser, MD, Chair of Neurology at the University of California, San Francisco School of Medicine, and colleagues conducted OPERA I and OPERA II, two phase III studies to investigate the safety and efficacy of ocrelizumab, compared with interferon beta-1a, in patients with relapsing-remitting MS. The trials had identical protocols, but were conducted at separate trial sites. Eligible participants were between ages 18 and 55, had an Expanded Disability Status Scale (EDSS) score no greater than 5.5 at screening, a history of relapses, and MRI abnormalities consistent with MS. Patients who previously had received a B-cell-targeted therapy or other immunosuppressive medication were excluded.

A total of 821 patients in OPERA I and 835 patients in OPERA II were randomized to 600 mg of IV ocrelizumab every 24 weeks or to 44 µg of subcutaneous interferon beta-1a three times weekly. The treatment period was 96 weeks. Each trial site had separate treating and examining investigators, all of whom were unaware of participants’ treatment assignments. The primary end point was the annualized relapse rate by 96 weeks. Secondary end points included the proportion of patients with disability progression confirmed at 12 weeks, the mean number of gadolinium-enhancing lesions identified on T1-weighted MRI, and the proportion of patients with disability improvement confirmed at 12 weeks.

The annualized relapse rate at 96 weeks in OPERA I was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. In OPERA II, the annualized relapse rate was 0.16 in the ocrelizumab group, compared with 0.29 in the interferon beta-1a group. These data suggest a 46% lower annualized relapse rate with ocrelizumab in OPERA I and a 47% lower rate with ocrelizumab in OPERA II.

The mean numbers of gadolinium-enhancing lesions in OPERA I were 0.02 with ocrelizumab versus 0.29 with interferon beta-1a. The numbers in OPERA II were 0.02 with ocrelizumab versus 0.42 with interferon beta-1a. The mean numbers of new or newly enlarged T2 hyperintense lesions in OPERA I were 0.32 with ocrelizumab and 1.41 with interferon beta-1a (ie, 77% fewer lesions with ocrelizumab). The values in OPERA II were 0.33 with ocrelizumab versus 1.90 with interferon beta-1a.

In a pooled analysis, 9.1% of patients in the ocrelizumab group had disability progression confirmed at 12 weeks, compared with 13.6% of patients in the interferon beta-1a group. The percentage of patients with disability improvement confirmed at 12 weeks was 20.7% in the ocrelizumab group, compared with 15.6% in the interferon beta-1a group (ie, a 33% higher rate of improvement with ocrelizumab). The effect of ocrelizumab on the rate of confirmed disability improvement was significant in OPERA I, but nonsignificant in OPERA II.

“Additional and extended studies will be required to determine whether the outcomes observed in these 96-week trials, including a near-complete cessation of new plaque formation, as assessed by MRI of the brain, translate into enhanced protection against accrual of disability over the long term,” said Dr. Hauser.

Ocrelizumab in Progressive MS

To examine the safety and efficacy of ocrelizumab in primary progressive MS, Xavier Montalban, MD, PhD, Chair of the Department of Neurology-Neuroimmunology and Director of the MS Centre of Catalonia at the Vall d’Hebron University Hospital in Barcelona, and colleagues conducted the phase III ORATORIO trial. Eligible patients were between ages 18 and 55 and had an EDSS score between 3.0 and 6.5 at screening. Patients with a history of relapsing-remitting MS, secondary progressive MS, or progressive relapsing MS were excluded, as were patients who had had previous treatment with B-cell-targeted therapies and other immunosuppressive medications.

Patients were randomized in a 2:1 ratio to receive 600 mg of IV ocrelizumab or matching placebo every 24 weeks. Double-blinded treatment was administered for at least 120 weeks. As in the OPERA trials, each trial site had separate treating and examining investigators. Patients who completed the blinded treatment phase were eligible to enter an open-label extension phase.

The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. Secondary end points included the percentage of patients with disability progression confirmed at 24 weeks, change in performance on the timed 25-foot walk from baseline to week 120, change in the total volume of brain lesions on T2-weighted MRI from baseline to week 120, change in brain volume from week 24 to week 120, and change in the Physical Component Summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), version 2, from baseline to week 120.

In all, 488 patients received ocrelizumab, and 244 received placebo. A total of 402 patients in the ocrelizumab arm and 174 controls completed the 120-week treatment period. The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo. The data suggest a 24% reduction in the risk of this outcome with ocrelizumab.

The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab and 35.7% with placebo (ie, a relative risk reduction of 25% with ocrelizumab). The mean change from baseline to week 120 in performance on the timed 25-foot walk was 38.9% with ocrelizumab versus 55.1% with placebo (ie, a relative reduction of 29.3% with ocrelizumab). The researchers found no significant between-group difference in the change in the SF-36 Physical Component Summary score from baseline to week 120.

In addition, the total volume of hyperintense lesions on T2-weighted images from baseline to week 120 decreased with ocrelizumab and increased with placebo (mean percent change, −3.4% vs 7.4%). The adjusted mean percent change in brain volume from week 24 to week 120 was lower with ocrelizumab than with placebo (–0.90% vs –1.09%).

Infusion-related reactions were more common in the ocrelizumab group than among controls. Neoplasms were reported in 11 of 486 patients (2.3%) in the ocrelizumab group and in two of 239 patients (0.8%) in the placebo group. “Safety will continue to be assessed throughout the open-label extension phase,” said Dr. Montalban.

Unknown Mechanism of Action

The mechanism by which B-cell depletion slows disability progression is not fully understood. It “may be multifunctional, because B cells have important roles in antibody secretion, antigen presentation, and the release of effector cytokines,” said Dr. Calabresi. By virtue of their number, B cells may be more important than other antigen-presenting cells in MS.

One potential reason that ocrelizumab showed positive effects in ORATORIO is that the patient population was relatively young (mean age, 45) and had active MRI scans (more than 25% of the population had gadolinium-enhancing lesions). These factors enabled the demonstration of a measurable anti-inflammatory effect of ocrelizumab in patients with inflammation at an early, reversible stage of the disease. “Another possible explanation is that B cells may mediate pathologic processes by secretion of cytokines or by deposition of immunoglobulins after they enter the CNS,” said Dr. Calabresi. “B cells and plasma cells secrete antibodies that may target CNS antigens such as myelin, neurons, and glia, which could accelerate neurodegeneration or inhibit myelin repair. The continued separation of disability progression curves in the ORATORIO trial beyond 52 weeks, when anti-inflammatory effects have been maximized, and success in the relatively noninflammatory disorder of primary progressive MS suggest that additional mechanisms of action may be operational, and further study is warranted.”

Because ocrelizumab appears to entail a higher risk of herpes reactivation and of neoplasms, “clinicians are urged to carefully consider which patients might benefit the most from ocrelizumab and to stay vigilant with regard to monitoring for side effects that could be managed effectively if detected early,” Dr. Calabresi concluded.

—Erik Greb

Suggested Reading

Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

Calabresi PA. B-cell depletion - a frontier in monoclonal antibodies for multiple sclerosis. N Engl J Med. 2016 Dec 21 [Epub ahead of print].

SNOWMASS, COLO. – Coronary artery bypass graft surgery in patients with severe ischemic left ventricular dysfunction is overdue for an upgrade in status in the American College of Cardiology/American Heart Association guidelines on the strength of the landmark STICH trial and its extended follow-up stage known as STICHES, according to Vinod H. Thourani, MD.

Currently, the guidelines give CABG in this large and growing population a class IIb recommendation, meaning it “might be considered.” This undervalues the study’s core lesson: “STICHES showed a clear survival benefit with CABG, so this most likely should become a class IIa recommendation,” Dr. Thourani said at the Annual Cardiovascular Conference at Snowmass.

He went on to describe how he applies the key study findings to individual patients.

[email protected]

SNOWMASS, COLO. – Coronary artery bypass graft surgery in patients with severe ischemic left ventricular dysfunction is overdue for an upgrade in status in the American College of Cardiology/American Heart Association guidelines on the strength of the landmark STICH trial and its extended follow-up stage known as STICHES, according to Vinod H. Thourani, MD.

Currently, the guidelines give CABG in this large and growing population a class IIb recommendation, meaning it “might be considered.” This undervalues the study’s core lesson: “STICHES showed a clear survival benefit with CABG, so this most likely should become a class IIa recommendation,” Dr. Thourani said at the Annual Cardiovascular Conference at Snowmass.

He went on to describe how he applies the key study findings to individual patients.

[email protected]

SNOWMASS, COLO. – Coronary artery bypass graft surgery in patients with severe ischemic left ventricular dysfunction is overdue for an upgrade in status in the American College of Cardiology/American Heart Association guidelines on the strength of the landmark STICH trial and its extended follow-up stage known as STICHES, according to Vinod H. Thourani, MD.

Currently, the guidelines give CABG in this large and growing population a class IIb recommendation, meaning it “might be considered.” This undervalues the study’s core lesson: “STICHES showed a clear survival benefit with CABG, so this most likely should become a class IIa recommendation,” Dr. Thourani said at the Annual Cardiovascular Conference at Snowmass.

He went on to describe how he applies the key study findings to individual patients.

[email protected]

PORTLAND, OR—The discovery that a small amount of electricity delivered to the brain could help treat patients with Parkinson’s disease surprised and delighted neuroscientists. Deep brain stimulation (DBS) can “change people’s lives,” which “creates a lot of expectation,” said Michael S. Okun, MD, Adelaide Lackner Professor and Chairman of Neurology at the University of Florida in Gainesville and National Medical Director of the Parkinson’s Foundation. “But let us not be fooled.… There are many shortcomings.”

Although DBS in its current form may be a powerful treatment for tremor, hyperkinesias, dyskinesias, and motor fluctuations, it is not an effective treatment for gait, freezing, balance, speech, and cognition, he said. As Dr. Okun tells patients, DBS likely will not address problems with “walking, talking, and thinking.”

Various studies indicate that understanding and appropriately managing patients’ expectations regarding DBS therapy is important for achieving optimal outcomes, Dr. Okun said in an overview at the Fourth World Parkinson Congress.

It is important for neurologists to align their expectations with patients’ up front. “What do they have an issue with that is impacting their ability to interface with their world?” he said. Then, the treatment team should tailor the operation to the patient.

Setting Realistic Expectations

Several tools, including the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) and another tool developed by Elena Moro, MD, PhD, Professor of Neurology, Grenoble Alpes University, France, can help identify appropriate candidates for DBS based on patient characteristics. Beyond such instruments, an interdisciplinary team, possibly including a neurologist, psychiatrist, neurosurgeon, and neuropsychologist, should identify a rationale for surgery and choose the best treatment approach. Patients who have contraindications (eg, those who have cognitive impairment or a tremor that does not respond to medication), are over age 70, or need palliation nevertheless may be candidates for DBS, Dr. Okun noted.

Research suggests that interdisciplinary screening may effectively identify patients at risk of poor outcomes. Higuchi et al found that the number and severity of concerns that were raised during interdisciplinary DBS evaluations correlated with unintended hospitalizations and worsened quality of life scores after surgery.

In addition, unrealistic expectations are associated with patients’ subjective outcomes. Maier et al interviewed 30 patients before and three months after surgery and classified patients according to whether their perceived outcome was negative, mixed, or positive. Eight patients with a subjective negative outcome had had unrealistic preoperative expectations, had no postsurgical improvement in quality of life, and had significantly higher presurgical and postsurgical apathy and depression scores. Preoperative apathy and depression predicted the subjective outcomes. Although preoperative apathy and depression are not often measured in clinical practice, “maybe it is something we should be thinking about,” Dr. Okun said.Nisenzon et al surveyed patients to evaluate which treatment outcomes were important to them. Pain, fatigue, emotional distress, walking, posture, and balance were among the domains that had high value to patients. These domains should be addressed with patients when discussing what they can anticipate after DBS surgery, Dr. Okun said.

Medication reduction is another issue that physicians should address with patients when discussing DBS. “A lot of people are expecting DBS to eliminate the need for medications,” which does not happen for 99% of patients, Dr. Okun said.

The National Parkinson Foundation has a free guide to DBS that includes a section detailing what patients can anticipate, he said. Dr. Okun and Pamela R. Zeilman, MSN, ANP-BC, DBS Clinical and Study Coordinator at the Center for Movement Disorders and Neurorestoration, updated the guide in 2014.

Perceptions Shift After Surgery

A study by Hariz et al found that patient perceptions of life shift after stimulation surgery. The investigators interviewed 13 patients who received pallidal DBS. Although certain physical symptoms improved, such as posture and spasms, patients reported that they encountered new challenges after surgery and expressed a need for counseling and support.

Furthermore, expectation may modulate the effect of DBS surgery. In one study, Keitel et al used different scripts to give patients the idea that they were to improve or not improve with various stimulation settings. In a subgroup of patients, tremor decreased or increased by at least 10%, compared with a control condition, when they received the verbal suggestions. Among those who responded to the negative suggestions, semantic verbal fluency also was significantly impaired. “There is an actual potency to the expectations of patients, and it matters how we interact with patients when we are evaluating them both in clinical practice and in the setting of a clinical trial,” Dr. Okun said.

Stimulation Targets and Technology

Multicenter randomized controlled studies of DBS targets have suggested reasons to choose particular stimulation targets over others. For example, stimulation of the subthalamic nucleus (STN) may be better for medication reduction, require fewer battery changes, and have a better economic profile. Meanwhile, stimulation of the globus pallidus internus (GPI) “is an outstanding dyskinesia suppressor … while STN tends to agitate dyskinesia.” GPI devices also may be easier to program.

Pedunculopontine nucleus (PPN) stimulation is a newer technique under investigation that may allow for additional leads to be placed in a patient’s brain. Leads can be implanted on one or both sides of the brain and can be used with GPI or STN leads.

Future DBS devices may enable the remote adjustment of stimulation settings. Nurses and patients also may be able to adjust the devices. DBS increasingly will be tailored to individuals’ symptoms and profiles, and devices may deliver scheduled, responsive, and smart stimulation, Dr. Okun said.

When any new device is introduced to the market, there is “a peak of inflated expectation” about the technology, Dr. Okun said. Then, expectations drop as people discover the device’s limitations. Finally, expectations increase and level as people come to better understand and use the technology. In Parkinson’s disease, neurologists and neurosurgeons are beginning to reach a “plateau of productivity where thousands of people can be helped” by current DBS therapies, he said.

—Jake Remaly

Suggested Reading

Hariz GM, Limousin P, Tisch S, et al. Patients’ perceptions of life shift after deep brain stimulation for primary dystonia--a qualitative study. Mov Disord. 2011;26(11):2101-2106.

Higuchi MA, Martinez-Ramirez D, Morita H, et al. Interdisciplinary Parkinson’s disease deep brain stimulation screening and the relationship to unintended hospitalizations and quality of life. PLoS One. 2016;11(5):e0153785.

Keitel A, Ferrea S, Südmeyer M, et al. Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson’s disease. PLoS One. 2013;8(12):e81878.

Maier F, Lewis CJ, Horstkoetter N, et al. Patients’ expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson’s disease: a mixed-method approach. J Neurol Neurosurg Psychiatry. 2013;84(11):1273-1281.

Nisenzon AN, Robinson ME, Bowers D, et al. Measurement of patient-centered outcomes in Parkinson’s disease: what do patients really want from their treatment? Parkinsonism Relat Disord. 2011;17(2):89-94.

PORTLAND, OR—The discovery that a small amount of electricity delivered to the brain could help treat patients with Parkinson’s disease surprised and delighted neuroscientists. Deep brain stimulation (DBS) can “change people’s lives,” which “creates a lot of expectation,” said Michael S. Okun, MD, Adelaide Lackner Professor and Chairman of Neurology at the University of Florida in Gainesville and National Medical Director of the Parkinson’s Foundation. “But let us not be fooled.… There are many shortcomings.”

Although DBS in its current form may be a powerful treatment for tremor, hyperkinesias, dyskinesias, and motor fluctuations, it is not an effective treatment for gait, freezing, balance, speech, and cognition, he said. As Dr. Okun tells patients, DBS likely will not address problems with “walking, talking, and thinking.”

Various studies indicate that understanding and appropriately managing patients’ expectations regarding DBS therapy is important for achieving optimal outcomes, Dr. Okun said in an overview at the Fourth World Parkinson Congress.

It is important for neurologists to align their expectations with patients’ up front. “What do they have an issue with that is impacting their ability to interface with their world?” he said. Then, the treatment team should tailor the operation to the patient.

Setting Realistic Expectations

Several tools, including the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) and another tool developed by Elena Moro, MD, PhD, Professor of Neurology, Grenoble Alpes University, France, can help identify appropriate candidates for DBS based on patient characteristics. Beyond such instruments, an interdisciplinary team, possibly including a neurologist, psychiatrist, neurosurgeon, and neuropsychologist, should identify a rationale for surgery and choose the best treatment approach. Patients who have contraindications (eg, those who have cognitive impairment or a tremor that does not respond to medication), are over age 70, or need palliation nevertheless may be candidates for DBS, Dr. Okun noted.

Research suggests that interdisciplinary screening may effectively identify patients at risk of poor outcomes. Higuchi et al found that the number and severity of concerns that were raised during interdisciplinary DBS evaluations correlated with unintended hospitalizations and worsened quality of life scores after surgery.

In addition, unrealistic expectations are associated with patients’ subjective outcomes. Maier et al interviewed 30 patients before and three months after surgery and classified patients according to whether their perceived outcome was negative, mixed, or positive. Eight patients with a subjective negative outcome had had unrealistic preoperative expectations, had no postsurgical improvement in quality of life, and had significantly higher presurgical and postsurgical apathy and depression scores. Preoperative apathy and depression predicted the subjective outcomes. Although preoperative apathy and depression are not often measured in clinical practice, “maybe it is something we should be thinking about,” Dr. Okun said.Nisenzon et al surveyed patients to evaluate which treatment outcomes were important to them. Pain, fatigue, emotional distress, walking, posture, and balance were among the domains that had high value to patients. These domains should be addressed with patients when discussing what they can anticipate after DBS surgery, Dr. Okun said.

Medication reduction is another issue that physicians should address with patients when discussing DBS. “A lot of people are expecting DBS to eliminate the need for medications,” which does not happen for 99% of patients, Dr. Okun said.

The National Parkinson Foundation has a free guide to DBS that includes a section detailing what patients can anticipate, he said. Dr. Okun and Pamela R. Zeilman, MSN, ANP-BC, DBS Clinical and Study Coordinator at the Center for Movement Disorders and Neurorestoration, updated the guide in 2014.

Perceptions Shift After Surgery

A study by Hariz et al found that patient perceptions of life shift after stimulation surgery. The investigators interviewed 13 patients who received pallidal DBS. Although certain physical symptoms improved, such as posture and spasms, patients reported that they encountered new challenges after surgery and expressed a need for counseling and support.

Furthermore, expectation may modulate the effect of DBS surgery. In one study, Keitel et al used different scripts to give patients the idea that they were to improve or not improve with various stimulation settings. In a subgroup of patients, tremor decreased or increased by at least 10%, compared with a control condition, when they received the verbal suggestions. Among those who responded to the negative suggestions, semantic verbal fluency also was significantly impaired. “There is an actual potency to the expectations of patients, and it matters how we interact with patients when we are evaluating them both in clinical practice and in the setting of a clinical trial,” Dr. Okun said.

Stimulation Targets and Technology

Multicenter randomized controlled studies of DBS targets have suggested reasons to choose particular stimulation targets over others. For example, stimulation of the subthalamic nucleus (STN) may be better for medication reduction, require fewer battery changes, and have a better economic profile. Meanwhile, stimulation of the globus pallidus internus (GPI) “is an outstanding dyskinesia suppressor … while STN tends to agitate dyskinesia.” GPI devices also may be easier to program.

Pedunculopontine nucleus (PPN) stimulation is a newer technique under investigation that may allow for additional leads to be placed in a patient’s brain. Leads can be implanted on one or both sides of the brain and can be used with GPI or STN leads.

Future DBS devices may enable the remote adjustment of stimulation settings. Nurses and patients also may be able to adjust the devices. DBS increasingly will be tailored to individuals’ symptoms and profiles, and devices may deliver scheduled, responsive, and smart stimulation, Dr. Okun said.

When any new device is introduced to the market, there is “a peak of inflated expectation” about the technology, Dr. Okun said. Then, expectations drop as people discover the device’s limitations. Finally, expectations increase and level as people come to better understand and use the technology. In Parkinson’s disease, neurologists and neurosurgeons are beginning to reach a “plateau of productivity where thousands of people can be helped” by current DBS therapies, he said.

—Jake Remaly

Suggested Reading

Hariz GM, Limousin P, Tisch S, et al. Patients’ perceptions of life shift after deep brain stimulation for primary dystonia--a qualitative study. Mov Disord. 2011;26(11):2101-2106.

Higuchi MA, Martinez-Ramirez D, Morita H, et al. Interdisciplinary Parkinson’s disease deep brain stimulation screening and the relationship to unintended hospitalizations and quality of life. PLoS One. 2016;11(5):e0153785.

Keitel A, Ferrea S, Südmeyer M, et al. Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson’s disease. PLoS One. 2013;8(12):e81878.

Maier F, Lewis CJ, Horstkoetter N, et al. Patients’ expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson’s disease: a mixed-method approach. J Neurol Neurosurg Psychiatry. 2013;84(11):1273-1281.

Nisenzon AN, Robinson ME, Bowers D, et al. Measurement of patient-centered outcomes in Parkinson’s disease: what do patients really want from their treatment? Parkinsonism Relat Disord. 2011;17(2):89-94.

PORTLAND, OR—The discovery that a small amount of electricity delivered to the brain could help treat patients with Parkinson’s disease surprised and delighted neuroscientists. Deep brain stimulation (DBS) can “change people’s lives,” which “creates a lot of expectation,” said Michael S. Okun, MD, Adelaide Lackner Professor and Chairman of Neurology at the University of Florida in Gainesville and National Medical Director of the Parkinson’s Foundation. “But let us not be fooled.… There are many shortcomings.”

Although DBS in its current form may be a powerful treatment for tremor, hyperkinesias, dyskinesias, and motor fluctuations, it is not an effective treatment for gait, freezing, balance, speech, and cognition, he said. As Dr. Okun tells patients, DBS likely will not address problems with “walking, talking, and thinking.”

Various studies indicate that understanding and appropriately managing patients’ expectations regarding DBS therapy is important for achieving optimal outcomes, Dr. Okun said in an overview at the Fourth World Parkinson Congress.

It is important for neurologists to align their expectations with patients’ up front. “What do they have an issue with that is impacting their ability to interface with their world?” he said. Then, the treatment team should tailor the operation to the patient.

Setting Realistic Expectations

Several tools, including the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) and another tool developed by Elena Moro, MD, PhD, Professor of Neurology, Grenoble Alpes University, France, can help identify appropriate candidates for DBS based on patient characteristics. Beyond such instruments, an interdisciplinary team, possibly including a neurologist, psychiatrist, neurosurgeon, and neuropsychologist, should identify a rationale for surgery and choose the best treatment approach. Patients who have contraindications (eg, those who have cognitive impairment or a tremor that does not respond to medication), are over age 70, or need palliation nevertheless may be candidates for DBS, Dr. Okun noted.

Research suggests that interdisciplinary screening may effectively identify patients at risk of poor outcomes. Higuchi et al found that the number and severity of concerns that were raised during interdisciplinary DBS evaluations correlated with unintended hospitalizations and worsened quality of life scores after surgery.

In addition, unrealistic expectations are associated with patients’ subjective outcomes. Maier et al interviewed 30 patients before and three months after surgery and classified patients according to whether their perceived outcome was negative, mixed, or positive. Eight patients with a subjective negative outcome had had unrealistic preoperative expectations, had no postsurgical improvement in quality of life, and had significantly higher presurgical and postsurgical apathy and depression scores. Preoperative apathy and depression predicted the subjective outcomes. Although preoperative apathy and depression are not often measured in clinical practice, “maybe it is something we should be thinking about,” Dr. Okun said.Nisenzon et al surveyed patients to evaluate which treatment outcomes were important to them. Pain, fatigue, emotional distress, walking, posture, and balance were among the domains that had high value to patients. These domains should be addressed with patients when discussing what they can anticipate after DBS surgery, Dr. Okun said.

Medication reduction is another issue that physicians should address with patients when discussing DBS. “A lot of people are expecting DBS to eliminate the need for medications,” which does not happen for 99% of patients, Dr. Okun said.

The National Parkinson Foundation has a free guide to DBS that includes a section detailing what patients can anticipate, he said. Dr. Okun and Pamela R. Zeilman, MSN, ANP-BC, DBS Clinical and Study Coordinator at the Center for Movement Disorders and Neurorestoration, updated the guide in 2014.

Perceptions Shift After Surgery

A study by Hariz et al found that patient perceptions of life shift after stimulation surgery. The investigators interviewed 13 patients who received pallidal DBS. Although certain physical symptoms improved, such as posture and spasms, patients reported that they encountered new challenges after surgery and expressed a need for counseling and support.

Furthermore, expectation may modulate the effect of DBS surgery. In one study, Keitel et al used different scripts to give patients the idea that they were to improve or not improve with various stimulation settings. In a subgroup of patients, tremor decreased or increased by at least 10%, compared with a control condition, when they received the verbal suggestions. Among those who responded to the negative suggestions, semantic verbal fluency also was significantly impaired. “There is an actual potency to the expectations of patients, and it matters how we interact with patients when we are evaluating them both in clinical practice and in the setting of a clinical trial,” Dr. Okun said.

Stimulation Targets and Technology

Multicenter randomized controlled studies of DBS targets have suggested reasons to choose particular stimulation targets over others. For example, stimulation of the subthalamic nucleus (STN) may be better for medication reduction, require fewer battery changes, and have a better economic profile. Meanwhile, stimulation of the globus pallidus internus (GPI) “is an outstanding dyskinesia suppressor … while STN tends to agitate dyskinesia.” GPI devices also may be easier to program.

Pedunculopontine nucleus (PPN) stimulation is a newer technique under investigation that may allow for additional leads to be placed in a patient’s brain. Leads can be implanted on one or both sides of the brain and can be used with GPI or STN leads.

Future DBS devices may enable the remote adjustment of stimulation settings. Nurses and patients also may be able to adjust the devices. DBS increasingly will be tailored to individuals’ symptoms and profiles, and devices may deliver scheduled, responsive, and smart stimulation, Dr. Okun said.

When any new device is introduced to the market, there is “a peak of inflated expectation” about the technology, Dr. Okun said. Then, expectations drop as people discover the device’s limitations. Finally, expectations increase and level as people come to better understand and use the technology. In Parkinson’s disease, neurologists and neurosurgeons are beginning to reach a “plateau of productivity where thousands of people can be helped” by current DBS therapies, he said.

—Jake Remaly

Suggested Reading

Hariz GM, Limousin P, Tisch S, et al. Patients’ perceptions of life shift after deep brain stimulation for primary dystonia--a qualitative study. Mov Disord. 2011;26(11):2101-2106.

Higuchi MA, Martinez-Ramirez D, Morita H, et al. Interdisciplinary Parkinson’s disease deep brain stimulation screening and the relationship to unintended hospitalizations and quality of life. PLoS One. 2016;11(5):e0153785.

Keitel A, Ferrea S, Südmeyer M, et al. Expectation modulates the effect of deep brain stimulation on motor and cognitive function in tremor-dominant Parkinson’s disease. PLoS One. 2013;8(12):e81878.

Maier F, Lewis CJ, Horstkoetter N, et al. Patients’ expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson’s disease: a mixed-method approach. J Neurol Neurosurg Psychiatry. 2013;84(11):1273-1281.

Nisenzon AN, Robinson ME, Bowers D, et al. Measurement of patient-centered outcomes in Parkinson’s disease: what do patients really want from their treatment? Parkinsonism Relat Disord. 2011;17(2):89-94.

Doctor evaluating a patient
Photo courtesy of CDC

The European LeukemiaNet (ELN) has released updated recommendations for the diagnosis and treatment of acute myeloid leukemia (AML) in adults.

The recommendations include revised ELN genetic categories, a proposed response category based on minimal residual disease status, and a proposed category for progressive disease for clinical trials.

They also include the updated World Health Organization classification of myeloid neoplasms and acute leukemia.

The recommendations are published in Blood.

“These guidelines are an important update of the current and widely used recommendations for managing AML, for constructing clinical trials, and for predicting outcomes of AML patients,” said Clara D. Bloomfield, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.

“They will be the new standard of care and will replace the 2010 ELN recommendations for managing AML patients and designing clinical trials.”

Dr Bloomfield said updating the ELN recommendations was prompted by new insights into the molecular and genomic causes of AML, by the development of new genetic tests and tests for detecting minimal residual disease, and by the development of novel anti-leukemic agents.

Changes of note, according to Dr Bloomfield, are that there are now 3 genetic risk categories rather than 4, and the FLT3-ITD mutation has been added as a marker of risk.

In addition, “complete remission with no evidence of minimal residual disease” is a new proposed response category. This criterion requires that genetic markers present at diagnosis are no longer detectable.

“It is no longer good enough to examine bone marrow samples and say the leukemia is gone,” Dr Bloomfield said. “We must also see the loss of genetic markers.”

Another change is that “progressive disease” is a new provisional response category to be used in clinical trials only. The purpose of the category is to harmonize the various definitions of progressive disease that are used in different clinical trials.

Doctor evaluating a patient
Photo courtesy of CDC

The European LeukemiaNet (ELN) has released updated recommendations for the diagnosis and treatment of acute myeloid leukemia (AML) in adults.

The recommendations include revised ELN genetic categories, a proposed response category based on minimal residual disease status, and a proposed category for progressive disease for clinical trials.

They also include the updated World Health Organization classification of myeloid neoplasms and acute leukemia.

The recommendations are published in Blood.

“These guidelines are an important update of the current and widely used recommendations for managing AML, for constructing clinical trials, and for predicting outcomes of AML patients,” said Clara D. Bloomfield, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.

“They will be the new standard of care and will replace the 2010 ELN recommendations for managing AML patients and designing clinical trials.”

Dr Bloomfield said updating the ELN recommendations was prompted by new insights into the molecular and genomic causes of AML, by the development of new genetic tests and tests for detecting minimal residual disease, and by the development of novel anti-leukemic agents.

Changes of note, according to Dr Bloomfield, are that there are now 3 genetic risk categories rather than 4, and the FLT3-ITD mutation has been added as a marker of risk.

In addition, “complete remission with no evidence of minimal residual disease” is a new proposed response category. This criterion requires that genetic markers present at diagnosis are no longer detectable.

“It is no longer good enough to examine bone marrow samples and say the leukemia is gone,” Dr Bloomfield said. “We must also see the loss of genetic markers.”

Another change is that “progressive disease” is a new provisional response category to be used in clinical trials only. The purpose of the category is to harmonize the various definitions of progressive disease that are used in different clinical trials.

Doctor evaluating a patient
Photo courtesy of CDC

The European LeukemiaNet (ELN) has released updated recommendations for the diagnosis and treatment of acute myeloid leukemia (AML) in adults.

The recommendations include revised ELN genetic categories, a proposed response category based on minimal residual disease status, and a proposed category for progressive disease for clinical trials.

They also include the updated World Health Organization classification of myeloid neoplasms and acute leukemia.

The recommendations are published in Blood.

“These guidelines are an important update of the current and widely used recommendations for managing AML, for constructing clinical trials, and for predicting outcomes of AML patients,” said Clara D. Bloomfield, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.

“They will be the new standard of care and will replace the 2010 ELN recommendations for managing AML patients and designing clinical trials.”

Dr Bloomfield said updating the ELN recommendations was prompted by new insights into the molecular and genomic causes of AML, by the development of new genetic tests and tests for detecting minimal residual disease, and by the development of novel anti-leukemic agents.

Changes of note, according to Dr Bloomfield, are that there are now 3 genetic risk categories rather than 4, and the FLT3-ITD mutation has been added as a marker of risk.

In addition, “complete remission with no evidence of minimal residual disease” is a new proposed response category. This criterion requires that genetic markers present at diagnosis are no longer detectable.

“It is no longer good enough to examine bone marrow samples and say the leukemia is gone,” Dr Bloomfield said. “We must also see the loss of genetic markers.”

Another change is that “progressive disease” is a new provisional response category to be used in clinical trials only. The purpose of the category is to harmonize the various definitions of progressive disease that are used in different clinical trials.

WAILEA, Hawaii – The Food and Drug Administration approval of oxymetazoline 1% cream for the background erythema of rosacea is big news for dermatologists and patients, according to Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit.

In studies, patients showed a two grade improvement in baseline erythema, and erythema reduction that lasted for 9-12 hours in many patients, said Dr. Stein Gold in a video interview, who was involved in the clinical trials.

“We have safety data that lasts up to an entire year, with no new safety signals,” and the incidence of exacerbation of erythema was rare, she added in a video interview at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation. Oxymetazoline 1% cream, which will be marketed as Rhofade by Allergan, was approved in January 2017 for the “topical treatment of persistent facial erythema associated with rosacea in adults.”

Dr. Stein Gold disclosed relationships with several companies, including Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Anacor, Medimetriks, Sol-Gel, and Promius.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – The Food and Drug Administration approval of oxymetazoline 1% cream for the background erythema of rosacea is big news for dermatologists and patients, according to Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit.

In studies, patients showed a two grade improvement in baseline erythema, and erythema reduction that lasted for 9-12 hours in many patients, said Dr. Stein Gold in a video interview, who was involved in the clinical trials.

“We have safety data that lasts up to an entire year, with no new safety signals,” and the incidence of exacerbation of erythema was rare, she added in a video interview at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation. Oxymetazoline 1% cream, which will be marketed as Rhofade by Allergan, was approved in January 2017 for the “topical treatment of persistent facial erythema associated with rosacea in adults.”

Dr. Stein Gold disclosed relationships with several companies, including Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Anacor, Medimetriks, Sol-Gel, and Promius.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – The Food and Drug Administration approval of oxymetazoline 1% cream for the background erythema of rosacea is big news for dermatologists and patients, according to Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit.

In studies, patients showed a two grade improvement in baseline erythema, and erythema reduction that lasted for 9-12 hours in many patients, said Dr. Stein Gold in a video interview, who was involved in the clinical trials.

“We have safety data that lasts up to an entire year, with no new safety signals,” and the incidence of exacerbation of erythema was rare, she added in a video interview at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation. Oxymetazoline 1% cream, which will be marketed as Rhofade by Allergan, was approved in January 2017 for the “topical treatment of persistent facial erythema associated with rosacea in adults.”

Dr. Stein Gold disclosed relationships with several companies, including Galderma, Leo, Novan, Valeant, Dermira, Novartis, Celgene, Allergan, Foamix, Anacor, Medimetriks, Sol-Gel, and Promius.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Combining methotrexate with a biologic is an off-label use for psoriasis patients but is supported by information from the psoriatic arthritis literature, said J. Mark Jackson, MD, of the University of Louisville (Ky.).

In fact, the combination treatment may improve symptoms in patients with both psoriasis and arthritis not well controlled with one drug, Dr. Jackson explained in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

As for dosage, “I do think we can use less methotrexate in combination” with a biologic for psoriasis when using methotrexate alone, he noted. “It’s like the addition of a spice to the right dish,” he added. Patients may need “just a little bit to get them over the edge and really get them to that efficacy point that creates the success that you need.”

Dr. Jackson disclosed financial relationships with companies including AbbVie, Amgen, Celgene, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and Top MD.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – Biosimilars are coming to dermatology, but their impact from a clinical and insurance standpoint has yet to be determined, according to Kenneth B. Gordon, MD, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

Biosimilars seem to have reasonably good efficacy, and safety to date has been “pretty consistent” with safety associated with the parent compounds, but a key issue will be how they are used in patients on anti-TNF agents who have been doing well over time, Dr. Gordon said in a video interview. Because these medicines cross react in terms of immunogenicity and are not quite the same, “trying to use them interchangeably, as many insurance companies will ask us to do, is going to be difficult,” he noted.

His concern does not apply to a new patient starting on a biosimilar. “The problem I see is when insurance companies and pharmacies start mandating us going back and forth between medicines, and running into difficulty with loss of effect of those drugs,” he explained. “It’s not a safety issue, it’s more of an issue of losing efficacy of a formerly active drug,” he said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Dr. Gordon disclosed financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Lilly, Celgene, Novartis, and Sun.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – While spironolactone is an old drug, it remains a safe and effective treatment option for acne in women, according to Julie Harper, MD, of the University of Alabama, Birmingham.

In a video interview, Dr. Harper said that she usually does not choose spironolactone as a first-line drug, “but more often than not this is a drug that is an add-on to other therapies” that have been tried. She tends to start with a low dose and titrates up based on side effects. The drug has been tested in men, but Dr. Harper cited a Japanese study that discontinued a male treatment arm because men developed gynecomastia.

In her opinion, it isn’t always necessary to routinely check potassium levels in patients on spironolactone. “In the vast majority of patients, I do not check labs routinely” before starting spironolactone, she said at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But she noted that some physicians feel more comfortable checking baseline labs.

Dr. Harper disclosed financial relationships with Allergan, Galderma, BioPharmX, La Roche-Posay, Promius, Valeant, and Bayer.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – While spironolactone is an old drug, it remains a safe and effective treatment option for acne in women, according to Julie Harper, MD, of the University of Alabama, Birmingham.

In a video interview, Dr. Harper said that she usually does not choose spironolactone as a first-line drug, “but more often than not this is a drug that is an add-on to other therapies” that have been tried. She tends to start with a low dose and titrates up based on side effects. The drug has been tested in men, but Dr. Harper cited a Japanese study that discontinued a male treatment arm because men developed gynecomastia.

In her opinion, it isn’t always necessary to routinely check potassium levels in patients on spironolactone. “In the vast majority of patients, I do not check labs routinely” before starting spironolactone, she said at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But she noted that some physicians feel more comfortable checking baseline labs.

Dr. Harper disclosed financial relationships with Allergan, Galderma, BioPharmX, La Roche-Posay, Promius, Valeant, and Bayer.

SDEF and this news organization are owned by the same parent organization.

WAILEA, Hawaii – While spironolactone is an old drug, it remains a safe and effective treatment option for acne in women, according to Julie Harper, MD, of the University of Alabama, Birmingham.

In a video interview, Dr. Harper said that she usually does not choose spironolactone as a first-line drug, “but more often than not this is a drug that is an add-on to other therapies” that have been tried. She tends to start with a low dose and titrates up based on side effects. The drug has been tested in men, but Dr. Harper cited a Japanese study that discontinued a male treatment arm because men developed gynecomastia.

In her opinion, it isn’t always necessary to routinely check potassium levels in patients on spironolactone. “In the vast majority of patients, I do not check labs routinely” before starting spironolactone, she said at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But she noted that some physicians feel more comfortable checking baseline labs.

Dr. Harper disclosed financial relationships with Allergan, Galderma, BioPharmX, La Roche-Posay, Promius, Valeant, and Bayer.

SDEF and this news organization are owned by the same parent organization.

HOUSTON – Parents of children with congenital heart disease cite survival statistics, surgeon-specific experience, and complication rates as the three most important congenital heart surgery outcome measures to report publicly, results from a large survey show.

“Recently, an increasing demand for the public reporting of pediatric heart surgery outcomes has led to the development of several different reporting schemes, including a hospital star rating system and procedure-specific mortality data tables for the Society of Thoracic Surgeons benchmark operations,” study investigator Mallory L. Irons, MD, said during a press briefing at the annual meeting of the Society of Thoracic Surgeons. “However, despite the availability of these reporting schemes, there remain unanswered questions about the optimal format and content of public reporting for pediatric heart surgery outcomes.”

[email protected]

HOUSTON – Parents of children with congenital heart disease cite survival statistics, surgeon-specific experience, and complication rates as the three most important congenital heart surgery outcome measures to report publicly, results from a large survey show.

“Recently, an increasing demand for the public reporting of pediatric heart surgery outcomes has led to the development of several different reporting schemes, including a hospital star rating system and procedure-specific mortality data tables for the Society of Thoracic Surgeons benchmark operations,” study investigator Mallory L. Irons, MD, said during a press briefing at the annual meeting of the Society of Thoracic Surgeons. “However, despite the availability of these reporting schemes, there remain unanswered questions about the optimal format and content of public reporting for pediatric heart surgery outcomes.”

[email protected]

HOUSTON – Parents of children with congenital heart disease cite survival statistics, surgeon-specific experience, and complication rates as the three most important congenital heart surgery outcome measures to report publicly, results from a large survey show.

“Recently, an increasing demand for the public reporting of pediatric heart surgery outcomes has led to the development of several different reporting schemes, including a hospital star rating system and procedure-specific mortality data tables for the Society of Thoracic Surgeons benchmark operations,” study investigator Mallory L. Irons, MD, said during a press briefing at the annual meeting of the Society of Thoracic Surgeons. “However, despite the availability of these reporting schemes, there remain unanswered questions about the optimal format and content of public reporting for pediatric heart surgery outcomes.”

[email protected]

ATLANTA – HIV-positive men who have sex with men should be getting vaccinated against invasive meningococcal disease twice, but an alarming majority are only getting vaccinated once, according to a new study presented at a conference on STD prevention sponsored the Centers for Disease Control and Prevention.

“This analysis underscores the need for active patient recall in order to maximize return for second dose among HIV-infected [men who have sex with men], although [that] may be resource-intensive,” said Kelly Jamison, MPH, of New York City’s department of health and mental hygiene.

Ms. Jamison and her coinvestigators examined medical record data of HIV-infected men who have sex with men who visited New York City STD clinics between Oct. 5, 2012 and Dec. 31, 2014, looking for individuals who received their first meningococcal vaccinations during that time period. The primary endpoint was to find the rate at which individuals who received the first vaccination came back within 1 year (Dec. 31, 2015) to receive a second vaccination.

The study was prompted by the invasive meningococcal disease (IMD) outbreak that New York City experienced from 2010-2013, in which 22 cases were identified in men who have sex with men, of which 55% involved men who were HIV-infected. All IMD cases involved serotype C, with a case fatality rate that was three times what public health officials anticipated at the time.

Because of this, the city launched a meningitis vaccination campaign. Vaccination was recommended for all men who have sex with men who were residents of New York City and had high-risk sexual exposure after Sept. 1, 2012. In early October, STD clinics around the city began offering free MCV4 vaccines. By late November, the recommendations were updated to include men who have sex with men who lived in specific parts of Brooklyn and had experienced high-risk sexual exposure after Sept. 1. In March 2013, the recommendations were further updated to state that all HIV-infected men who have sex with men and all such men with high-risk sexual exposure should be vaccinated. In August 2013, after the outbreak was over, the recommendations were updated one last time to state that they were recommendations for “ongoing vaccination.”

“A single dose of MCV4 is not sufficient for HIV-infected persons, so a second dose is recommended to occur 8 weeks after the first dose, and in order to increase two-dose coverage among HIV-infected MSM, STD clinicians provided the date for person to return for their second dose on a vaccine card given to patients at time of their first dose,” Ms. Jamison explained.

In total, 1,212 individuals were included in study. Over the course of the study period, only 322 (26.6%) returned within 1 year for a second vaccination. In terms of individual years, 2012 experienced the highest rate of second vaccination returns, at 38.6% (P less than .001). Of the 322 who received the second vaccination, 144 (44.7%) came to the STD clinic specifically for the second dose, 69 (21.4%) asked for the second vaccination along with other STD services, and 109 (33.9%) were “opportunistically vaccinated while presenting for other services.”

Older men who have sex with men were more likely to return for their second vaccination, as only 63 (18%) of those who did were under the age of 30. Those aged between 30 and 39 years numbered 80 (23%), those between 40 and 49 years numbered 102 (33%), and those aged 50 years or older numbered 77 (40%), meaning that older men were two to three times more likely to get that second dose (P less than .001).

“We did see suboptimal return for second doses, but this may be an underestimate, [because] we were unable to capture second doses received at non-STD clinic providers,” Ms. Jamison noted.

Ms. Jamison did not report any financial disclosures for this study.

[email protected]

ATLANTA – HIV-positive men who have sex with men should be getting vaccinated against invasive meningococcal disease twice, but an alarming majority are only getting vaccinated once, according to a new study presented at a conference on STD prevention sponsored the Centers for Disease Control and Prevention.

“This analysis underscores the need for active patient recall in order to maximize return for second dose among HIV-infected [men who have sex with men], although [that] may be resource-intensive,” said Kelly Jamison, MPH, of New York City’s department of health and mental hygiene.

Ms. Jamison and her coinvestigators examined medical record data of HIV-infected men who have sex with men who visited New York City STD clinics between Oct. 5, 2012 and Dec. 31, 2014, looking for individuals who received their first meningococcal vaccinations during that time period. The primary endpoint was to find the rate at which individuals who received the first vaccination came back within 1 year (Dec. 31, 2015) to receive a second vaccination.

The study was prompted by the invasive meningococcal disease (IMD) outbreak that New York City experienced from 2010-2013, in which 22 cases were identified in men who have sex with men, of which 55% involved men who were HIV-infected. All IMD cases involved serotype C, with a case fatality rate that was three times what public health officials anticipated at the time.

Because of this, the city launched a meningitis vaccination campaign. Vaccination was recommended for all men who have sex with men who were residents of New York City and had high-risk sexual exposure after Sept. 1, 2012. In early October, STD clinics around the city began offering free MCV4 vaccines. By late November, the recommendations were updated to include men who have sex with men who lived in specific parts of Brooklyn and had experienced high-risk sexual exposure after Sept. 1. In March 2013, the recommendations were further updated to state that all HIV-infected men who have sex with men and all such men with high-risk sexual exposure should be vaccinated. In August 2013, after the outbreak was over, the recommendations were updated one last time to state that they were recommendations for “ongoing vaccination.”

“A single dose of MCV4 is not sufficient for HIV-infected persons, so a second dose is recommended to occur 8 weeks after the first dose, and in order to increase two-dose coverage among HIV-infected MSM, STD clinicians provided the date for person to return for their second dose on a vaccine card given to patients at time of their first dose,” Ms. Jamison explained.

In total, 1,212 individuals were included in study. Over the course of the study period, only 322 (26.6%) returned within 1 year for a second vaccination. In terms of individual years, 2012 experienced the highest rate of second vaccination returns, at 38.6% (P less than .001). Of the 322 who received the second vaccination, 144 (44.7%) came to the STD clinic specifically for the second dose, 69 (21.4%) asked for the second vaccination along with other STD services, and 109 (33.9%) were “opportunistically vaccinated while presenting for other services.”

Older men who have sex with men were more likely to return for their second vaccination, as only 63 (18%) of those who did were under the age of 30. Those aged between 30 and 39 years numbered 80 (23%), those between 40 and 49 years numbered 102 (33%), and those aged 50 years or older numbered 77 (40%), meaning that older men were two to three times more likely to get that second dose (P less than .001).

“We did see suboptimal return for second doses, but this may be an underestimate, [because] we were unable to capture second doses received at non-STD clinic providers,” Ms. Jamison noted.

Ms. Jamison did not report any financial disclosures for this study.

[email protected]

ATLANTA – HIV-positive men who have sex with men should be getting vaccinated against invasive meningococcal disease twice, but an alarming majority are only getting vaccinated once, according to a new study presented at a conference on STD prevention sponsored the Centers for Disease Control and Prevention.

“This analysis underscores the need for active patient recall in order to maximize return for second dose among HIV-infected [men who have sex with men], although [that] may be resource-intensive,” said Kelly Jamison, MPH, of New York City’s department of health and mental hygiene.

Ms. Jamison and her coinvestigators examined medical record data of HIV-infected men who have sex with men who visited New York City STD clinics between Oct. 5, 2012 and Dec. 31, 2014, looking for individuals who received their first meningococcal vaccinations during that time period. The primary endpoint was to find the rate at which individuals who received the first vaccination came back within 1 year (Dec. 31, 2015) to receive a second vaccination.

The study was prompted by the invasive meningococcal disease (IMD) outbreak that New York City experienced from 2010-2013, in which 22 cases were identified in men who have sex with men, of which 55% involved men who were HIV-infected. All IMD cases involved serotype C, with a case fatality rate that was three times what public health officials anticipated at the time.

Because of this, the city launched a meningitis vaccination campaign. Vaccination was recommended for all men who have sex with men who were residents of New York City and had high-risk sexual exposure after Sept. 1, 2012. In early October, STD clinics around the city began offering free MCV4 vaccines. By late November, the recommendations were updated to include men who have sex with men who lived in specific parts of Brooklyn and had experienced high-risk sexual exposure after Sept. 1. In March 2013, the recommendations were further updated to state that all HIV-infected men who have sex with men and all such men with high-risk sexual exposure should be vaccinated. In August 2013, after the outbreak was over, the recommendations were updated one last time to state that they were recommendations for “ongoing vaccination.”

“A single dose of MCV4 is not sufficient for HIV-infected persons, so a second dose is recommended to occur 8 weeks after the first dose, and in order to increase two-dose coverage among HIV-infected MSM, STD clinicians provided the date for person to return for their second dose on a vaccine card given to patients at time of their first dose,” Ms. Jamison explained.

In total, 1,212 individuals were included in study. Over the course of the study period, only 322 (26.6%) returned within 1 year for a second vaccination. In terms of individual years, 2012 experienced the highest rate of second vaccination returns, at 38.6% (P less than .001). Of the 322 who received the second vaccination, 144 (44.7%) came to the STD clinic specifically for the second dose, 69 (21.4%) asked for the second vaccination along with other STD services, and 109 (33.9%) were “opportunistically vaccinated while presenting for other services.”

Older men who have sex with men were more likely to return for their second vaccination, as only 63 (18%) of those who did were under the age of 30. Those aged between 30 and 39 years numbered 80 (23%), those between 40 and 49 years numbered 102 (33%), and those aged 50 years or older numbered 77 (40%), meaning that older men were two to three times more likely to get that second dose (P less than .001).

“We did see suboptimal return for second doses, but this may be an underestimate, [because] we were unable to capture second doses received at non-STD clinic providers,” Ms. Jamison noted.

Ms. Jamison did not report any financial disclosures for this study.

[email protected]