SAN FRANCISCO – A sweep of new agents are poised to deliver what could be a knock-out blow to multiple myeloma, according to the director of the myeloma program at the University of California, San Francisco.

Some are second- or third-generation agents in a mainstay class that appear to have less toxicity than and/or overcome resistance to their predecessors, Dr. Jeffrey L. Wolf said at the annual Oncology Congress here. Others come from classes not previously used in this disease.

"There is a rush to develop new drugs in myeloma," Dr. Wolf told attendees. "We [understand] some mechanisms that the disease seems to favor, so we can interfere with those."

The prospects, in turn, are excellent: "We have made such tremendous headway in myeloma, except for those exceptional cases with 17p deletions and some other adverse prognostic features," he said. "As a disease, it seems to be on the ropes."

A Less-Toxic Proteasome Inhibitor

The first-generation proteasome inhibitor bortezomib (Velcade) improves myeloma outcomes, but maximizing its benefit will require addressing the peripheral neuropathy that limits its use. Three strategies may lessen this toxicity without compromising efficacy, Dr. Wolf suggested: modestly reducing the standard dose, adjusting the schedule from twice to once weekly, and altering the route of administration from intravenous to subcutaneous.

For example, in patients with pretreated myeloma, giving bortezomib subcutaneously instead of intravenously results in an identical overall response rate of 52% (Lancet Oncol. 2011;12:431-40). But there are significant reductions in rates of peripheral neuropathy of any grade (38% vs. 53%) and grade 3 or higher (6% vs. 16%).

"Practically everybody that we see now at UCSF gets subcutaneous [bortezomib]," Dr. Wolf said. It’s a great way to go back and treat patients who maybe otherwise have stopped their therapy because of their neuropathy."

Carfilzomib, an investigational next-generation proteasome inhibitor in phase III trials, is showing good antimyeloma activity and a low rate of peripheral neuropathy. Among patients with pretreated, relapsed, or refractory disease, carfilzomib monotherapy achieved overall response rates of 42% to 53% in a bortezomib-naive group (ASCO 2011 annual meeting. Abstract 8026) and 21% in a bortezomib-exposed group (Haematologica 2010;95:452 Abstract 1099). Median time to progression was at least 8 months for both.

Dr. Wolf said that unpublished data suggest that the response rate was still 17% specifically among patients who had had progression on bortezomib, "so there appears to be some activity in patients who are already refractory to a prior proteasome inhibitor."

Meanwhile, the rates of grade 1/2 and grade 3 peripheral neuropathy were 6% and 1%, respectively. And only a single patient of the 155 had to stop treatment because of this adverse effect.

When carfilzomib is combined with lenalidomide-dexamethasone (the so-called CRd regimen), the overall response rate in patients with pretreated, relapsed, and refractory disease is 78%, and the rate of complete or near complete response is 24% (ASCO 2011 meeting. Abstract 8025).

And, in newly diagnosed myeloma, among 18 patients receiving eight cycles of CRd, the overall response rate was 100%, and the rate of stringent-complete, complete, or near-complete response was 61% (2011 International Myeloma Workshop. Poster P-253). "This is very, very exciting—I don’t think we’ve seen this in any other combination," Dr. Wolf commented. "But these are small numbers of patients; we still need to increase the numbers of patients studied with this combination."

Bortezomib and carfilzomib may soon have company from several investigational proteasome inhibitors available in oral formulations that have shown promise in preclinical testing or have advanced to clinical trials: CEP-18770 (Cephalon), ONX-0912 (Onyx), and MLN-9708 (Millenium).

A Third-Generation IMiD in Trials

Pomalidomide, a third-generation immunomodulatory drug (IMiD), coming after thalidomide (Thalomid), and lenalidomide (Revlimid), is also showing good antimyeloma activity in clinical trials, according to Dr. Wolf.

Among patients with pretreated myeloma, the rate of partial or better response when pomalidomide is combined with dexamethasone has ranged from 25% to 42%, depending on the trial and patient population. Adverse events are primarily hematologic.

And in patients who have previously received lenalidomide, the response rate is similar, at 35% (ASCO 2011 annual meeting. Abstract 8067). "So, as with carfilzomib, where there appear to be responses in patients who have prior resistance to bortezomib, it appears that pomalidomide can give us responses in patients who have already had resistance to lenalidomide," he said.

HDAC Inhibitors Show Activity

The histone deacetylase (HDAC) inhibitor vorinostat (Zolinza) is approved for treatment of lymphoma. But it is being tested in clinical trials for myeloma, in combination therapy, with promising results, according to Dr. Wolf. Overall response rates have ranged from 40% to 94%, depending on the patient population and combination.

Similarly, the HDAC inhibitor romidepsin (Istodax) is approved for lymphoma treatment but is also being studied for antimyeloma activity. And panobinostat, an investigational member of this drug class, is being evaluated as a component of combination therapy in phase II and III myeloma trials.

Monoclonal Antibodies Tested

Elotuzumab is an investigational monoclonal antibody directed against CS1, a glycoprotein that is highly expressed on the surface of plasma cells and implicated in myeloma pathogenesis.

In a phase I trial among patients with relapsed or refractory myeloma, the combination of elotuzumab with lenalidomide and low-dose dexamethasone yielded an overall response rate of 82% (ASCO 2011 meeting. Abstract 8076). The rate was 83% among the subset of patients whose disease was refractory to the most recent therapy and 95% among the subset of lenalidomide-naive patients.

The combination of elotuzumab with bortezomib has also been tested in patients with relapsed or refractory myeloma. But the overall response rate with this combination was less impressive, at 48% (ASH 2010 meeting. Abstract 3023).

Other Agents and Pathways

Several other agents are being eyed for roles in myeloma therapy as well. They include bendamustine (Treanda), an old drug initially revived for lymphoma treatment; aurora kinase inhibitors (for example, MLN-8237); and inhibitors of the mammalian target of rapamycin, or mTOR (for example, INK-128).

Additionally, there is considerable interest in agents that target fibroblast growth factor receptor 3 (FGFR3) for one subgroup. "In patients with the 4;14 translocation, FGFR3 is overexpressed," Dr. Wolf explained. "Finding an inhibitor for that or a direct antibody ... may be quite effective in those patients."

Investigators are also assessing the impact of targeting certain signaling pathways, such as the Jak/Stat pathway and the AKT pathway. For instance, a phase III trial is testing perifosine, an investigational AKT inhibitor, in combination therapy among patients with relapsed or refractory myeloma (NCT01002248).

The Oncology Congress is presented by Reed Medical Education. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Dr. Wolf disclosed that he is on the speakers bureaus of Millenium, Celgene, and Ortho-Biotech, and is a consultant to and speaker for Onyx.

SAN FRANCISCO – A sweep of new agents are poised to deliver what could be a knock-out blow to multiple myeloma, according to the director of the myeloma program at the University of California, San Francisco.

Some are second- or third-generation agents in a mainstay class that appear to have less toxicity than and/or overcome resistance to their predecessors, Dr. Jeffrey L. Wolf said at the annual Oncology Congress here. Others come from classes not previously used in this disease.

"There is a rush to develop new drugs in myeloma," Dr. Wolf told attendees. "We [understand] some mechanisms that the disease seems to favor, so we can interfere with those."

The prospects, in turn, are excellent: "We have made such tremendous headway in myeloma, except for those exceptional cases with 17p deletions and some other adverse prognostic features," he said. "As a disease, it seems to be on the ropes."

A Less-Toxic Proteasome Inhibitor

The first-generation proteasome inhibitor bortezomib (Velcade) improves myeloma outcomes, but maximizing its benefit will require addressing the peripheral neuropathy that limits its use. Three strategies may lessen this toxicity without compromising efficacy, Dr. Wolf suggested: modestly reducing the standard dose, adjusting the schedule from twice to once weekly, and altering the route of administration from intravenous to subcutaneous.

For example, in patients with pretreated myeloma, giving bortezomib subcutaneously instead of intravenously results in an identical overall response rate of 52% (Lancet Oncol. 2011;12:431-40). But there are significant reductions in rates of peripheral neuropathy of any grade (38% vs. 53%) and grade 3 or higher (6% vs. 16%).

"Practically everybody that we see now at UCSF gets subcutaneous [bortezomib]," Dr. Wolf said. It’s a great way to go back and treat patients who maybe otherwise have stopped their therapy because of their neuropathy."

Carfilzomib, an investigational next-generation proteasome inhibitor in phase III trials, is showing good antimyeloma activity and a low rate of peripheral neuropathy. Among patients with pretreated, relapsed, or refractory disease, carfilzomib monotherapy achieved overall response rates of 42% to 53% in a bortezomib-naive group (ASCO 2011 annual meeting. Abstract 8026) and 21% in a bortezomib-exposed group (Haematologica 2010;95:452 Abstract 1099). Median time to progression was at least 8 months for both.

Dr. Wolf said that unpublished data suggest that the response rate was still 17% specifically among patients who had had progression on bortezomib, "so there appears to be some activity in patients who are already refractory to a prior proteasome inhibitor."

Meanwhile, the rates of grade 1/2 and grade 3 peripheral neuropathy were 6% and 1%, respectively. And only a single patient of the 155 had to stop treatment because of this adverse effect.

When carfilzomib is combined with lenalidomide-dexamethasone (the so-called CRd regimen), the overall response rate in patients with pretreated, relapsed, and refractory disease is 78%, and the rate of complete or near complete response is 24% (ASCO 2011 meeting. Abstract 8025).

And, in newly diagnosed myeloma, among 18 patients receiving eight cycles of CRd, the overall response rate was 100%, and the rate of stringent-complete, complete, or near-complete response was 61% (2011 International Myeloma Workshop. Poster P-253). "This is very, very exciting—I don’t think we’ve seen this in any other combination," Dr. Wolf commented. "But these are small numbers of patients; we still need to increase the numbers of patients studied with this combination."

Bortezomib and carfilzomib may soon have company from several investigational proteasome inhibitors available in oral formulations that have shown promise in preclinical testing or have advanced to clinical trials: CEP-18770 (Cephalon), ONX-0912 (Onyx), and MLN-9708 (Millenium).

A Third-Generation IMiD in Trials

Pomalidomide, a third-generation immunomodulatory drug (IMiD), coming after thalidomide (Thalomid), and lenalidomide (Revlimid), is also showing good antimyeloma activity in clinical trials, according to Dr. Wolf.

Among patients with pretreated myeloma, the rate of partial or better response when pomalidomide is combined with dexamethasone has ranged from 25% to 42%, depending on the trial and patient population. Adverse events are primarily hematologic.

And in patients who have previously received lenalidomide, the response rate is similar, at 35% (ASCO 2011 annual meeting. Abstract 8067). "So, as with carfilzomib, where there appear to be responses in patients who have prior resistance to bortezomib, it appears that pomalidomide can give us responses in patients who have already had resistance to lenalidomide," he said.

HDAC Inhibitors Show Activity

The histone deacetylase (HDAC) inhibitor vorinostat (Zolinza) is approved for treatment of lymphoma. But it is being tested in clinical trials for myeloma, in combination therapy, with promising results, according to Dr. Wolf. Overall response rates have ranged from 40% to 94%, depending on the patient population and combination.

Similarly, the HDAC inhibitor romidepsin (Istodax) is approved for lymphoma treatment but is also being studied for antimyeloma activity. And panobinostat, an investigational member of this drug class, is being evaluated as a component of combination therapy in phase II and III myeloma trials.

Monoclonal Antibodies Tested

Elotuzumab is an investigational monoclonal antibody directed against CS1, a glycoprotein that is highly expressed on the surface of plasma cells and implicated in myeloma pathogenesis.

In a phase I trial among patients with relapsed or refractory myeloma, the combination of elotuzumab with lenalidomide and low-dose dexamethasone yielded an overall response rate of 82% (ASCO 2011 meeting. Abstract 8076). The rate was 83% among the subset of patients whose disease was refractory to the most recent therapy and 95% among the subset of lenalidomide-naive patients.

The combination of elotuzumab with bortezomib has also been tested in patients with relapsed or refractory myeloma. But the overall response rate with this combination was less impressive, at 48% (ASH 2010 meeting. Abstract 3023).

Other Agents and Pathways

Several other agents are being eyed for roles in myeloma therapy as well. They include bendamustine (Treanda), an old drug initially revived for lymphoma treatment; aurora kinase inhibitors (for example, MLN-8237); and inhibitors of the mammalian target of rapamycin, or mTOR (for example, INK-128).

Additionally, there is considerable interest in agents that target fibroblast growth factor receptor 3 (FGFR3) for one subgroup. "In patients with the 4;14 translocation, FGFR3 is overexpressed," Dr. Wolf explained. "Finding an inhibitor for that or a direct antibody ... may be quite effective in those patients."

Investigators are also assessing the impact of targeting certain signaling pathways, such as the Jak/Stat pathway and the AKT pathway. For instance, a phase III trial is testing perifosine, an investigational AKT inhibitor, in combination therapy among patients with relapsed or refractory myeloma (NCT01002248).

The Oncology Congress is presented by Reed Medical Education. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Dr. Wolf disclosed that he is on the speakers bureaus of Millenium, Celgene, and Ortho-Biotech, and is a consultant to and speaker for Onyx.

SAN FRANCISCO – A sweep of new agents are poised to deliver what could be a knock-out blow to multiple myeloma, according to the director of the myeloma program at the University of California, San Francisco.

Some are second- or third-generation agents in a mainstay class that appear to have less toxicity than and/or overcome resistance to their predecessors, Dr. Jeffrey L. Wolf said at the annual Oncology Congress here. Others come from classes not previously used in this disease.

"There is a rush to develop new drugs in myeloma," Dr. Wolf told attendees. "We [understand] some mechanisms that the disease seems to favor, so we can interfere with those."

The prospects, in turn, are excellent: "We have made such tremendous headway in myeloma, except for those exceptional cases with 17p deletions and some other adverse prognostic features," he said. "As a disease, it seems to be on the ropes."

A Less-Toxic Proteasome Inhibitor

The first-generation proteasome inhibitor bortezomib (Velcade) improves myeloma outcomes, but maximizing its benefit will require addressing the peripheral neuropathy that limits its use. Three strategies may lessen this toxicity without compromising efficacy, Dr. Wolf suggested: modestly reducing the standard dose, adjusting the schedule from twice to once weekly, and altering the route of administration from intravenous to subcutaneous.

For example, in patients with pretreated myeloma, giving bortezomib subcutaneously instead of intravenously results in an identical overall response rate of 52% (Lancet Oncol. 2011;12:431-40). But there are significant reductions in rates of peripheral neuropathy of any grade (38% vs. 53%) and grade 3 or higher (6% vs. 16%).

"Practically everybody that we see now at UCSF gets subcutaneous [bortezomib]," Dr. Wolf said. It’s a great way to go back and treat patients who maybe otherwise have stopped their therapy because of their neuropathy."

Carfilzomib, an investigational next-generation proteasome inhibitor in phase III trials, is showing good antimyeloma activity and a low rate of peripheral neuropathy. Among patients with pretreated, relapsed, or refractory disease, carfilzomib monotherapy achieved overall response rates of 42% to 53% in a bortezomib-naive group (ASCO 2011 annual meeting. Abstract 8026) and 21% in a bortezomib-exposed group (Haematologica 2010;95:452 Abstract 1099). Median time to progression was at least 8 months for both.

Dr. Wolf said that unpublished data suggest that the response rate was still 17% specifically among patients who had had progression on bortezomib, "so there appears to be some activity in patients who are already refractory to a prior proteasome inhibitor."

Meanwhile, the rates of grade 1/2 and grade 3 peripheral neuropathy were 6% and 1%, respectively. And only a single patient of the 155 had to stop treatment because of this adverse effect.

When carfilzomib is combined with lenalidomide-dexamethasone (the so-called CRd regimen), the overall response rate in patients with pretreated, relapsed, and refractory disease is 78%, and the rate of complete or near complete response is 24% (ASCO 2011 meeting. Abstract 8025).

And, in newly diagnosed myeloma, among 18 patients receiving eight cycles of CRd, the overall response rate was 100%, and the rate of stringent-complete, complete, or near-complete response was 61% (2011 International Myeloma Workshop. Poster P-253). "This is very, very exciting—I don’t think we’ve seen this in any other combination," Dr. Wolf commented. "But these are small numbers of patients; we still need to increase the numbers of patients studied with this combination."

Bortezomib and carfilzomib may soon have company from several investigational proteasome inhibitors available in oral formulations that have shown promise in preclinical testing or have advanced to clinical trials: CEP-18770 (Cephalon), ONX-0912 (Onyx), and MLN-9708 (Millenium).

A Third-Generation IMiD in Trials

Pomalidomide, a third-generation immunomodulatory drug (IMiD), coming after thalidomide (Thalomid), and lenalidomide (Revlimid), is also showing good antimyeloma activity in clinical trials, according to Dr. Wolf.

Among patients with pretreated myeloma, the rate of partial or better response when pomalidomide is combined with dexamethasone has ranged from 25% to 42%, depending on the trial and patient population. Adverse events are primarily hematologic.

And in patients who have previously received lenalidomide, the response rate is similar, at 35% (ASCO 2011 annual meeting. Abstract 8067). "So, as with carfilzomib, where there appear to be responses in patients who have prior resistance to bortezomib, it appears that pomalidomide can give us responses in patients who have already had resistance to lenalidomide," he said.

HDAC Inhibitors Show Activity

The histone deacetylase (HDAC) inhibitor vorinostat (Zolinza) is approved for treatment of lymphoma. But it is being tested in clinical trials for myeloma, in combination therapy, with promising results, according to Dr. Wolf. Overall response rates have ranged from 40% to 94%, depending on the patient population and combination.

Similarly, the HDAC inhibitor romidepsin (Istodax) is approved for lymphoma treatment but is also being studied for antimyeloma activity. And panobinostat, an investigational member of this drug class, is being evaluated as a component of combination therapy in phase II and III myeloma trials.

Monoclonal Antibodies Tested

Elotuzumab is an investigational monoclonal antibody directed against CS1, a glycoprotein that is highly expressed on the surface of plasma cells and implicated in myeloma pathogenesis.

In a phase I trial among patients with relapsed or refractory myeloma, the combination of elotuzumab with lenalidomide and low-dose dexamethasone yielded an overall response rate of 82% (ASCO 2011 meeting. Abstract 8076). The rate was 83% among the subset of patients whose disease was refractory to the most recent therapy and 95% among the subset of lenalidomide-naive patients.

The combination of elotuzumab with bortezomib has also been tested in patients with relapsed or refractory myeloma. But the overall response rate with this combination was less impressive, at 48% (ASH 2010 meeting. Abstract 3023).

Other Agents and Pathways

Several other agents are being eyed for roles in myeloma therapy as well. They include bendamustine (Treanda), an old drug initially revived for lymphoma treatment; aurora kinase inhibitors (for example, MLN-8237); and inhibitors of the mammalian target of rapamycin, or mTOR (for example, INK-128).

Additionally, there is considerable interest in agents that target fibroblast growth factor receptor 3 (FGFR3) for one subgroup. "In patients with the 4;14 translocation, FGFR3 is overexpressed," Dr. Wolf explained. "Finding an inhibitor for that or a direct antibody ... may be quite effective in those patients."

Investigators are also assessing the impact of targeting certain signaling pathways, such as the Jak/Stat pathway and the AKT pathway. For instance, a phase III trial is testing perifosine, an investigational AKT inhibitor, in combination therapy among patients with relapsed or refractory myeloma (NCT01002248).

The Oncology Congress is presented by Reed Medical Education. Reed Medical Education and this news organization are owned by Reed Elsevier Inc.

Dr. Wolf disclosed that he is on the speakers bureaus of Millenium, Celgene, and Ortho-Biotech, and is a consultant to and speaker for Onyx.

You’re ready to discharge a patient, but you don’t know whether the medication you’ve ordered will be available in the outpatient setting. Who do you ask? Your pharmacy service will have the answers, and if you’ve established a collegial relationship with the pharmacists there, most likely you can get a quick answer via page, text, or phone call. But if you don’t have personal contact with your pharmacists, chances are the interchange will impersonal—and that could mean missing ou

“Pharmacists may be underutilized, especially if the range of clinical services they offer are not recognized,” notes Kristine Gleason, RPh, clinical quality leader at Northwestern Memorial Hospital in Chicago. “We can be an excellent resource for young hospitalists and clinicians, offering information on clinical dosing and monitoring of complex, high-risk medications.”

Pharmacists also can be valuable resources for medication reconciliation and patient counseling, Gleason says, adding that “our goal is to work collaboratively with our clinicians to help ensure patients receive evidence-based medication regimens that are safe and without error and that are tailored to each patient’s individualized characteristics.”

Benefits of Rounding

Interactions between hospital pharmacies and HM services vary by institution size and organization. Roberta Barber, PharmD, MPH, is assistant vice president of pharmacy for Virtua Health’s four hospital campuses in New Jersey. At Memorial Hospital, where Erik DeLue, MD, MBA, SFHM, first established a hospitalist program, pharmacists are present in the ICU units and participate in care-coordination rounds.

Barber is crafting policies to extend the decentralized pharmacist model to all of Virtua’s hospitals. Equipped with cordless phones and tablet computers, pharmacists will be able to round with the HM team without sacrificing availability to other physicians and hospital staff. In this way, she says, “physicians will be able to consult with pharmacists as they’re creating their treatment plans, and the pharmacist can intervene regarding potential problem orders right then and there.”

At the University of California at San Francisco Medical Center, clinical pharmacists in the general medicine division work closely with the nine medicine teams run by hospitalists. That means 24/7 availability by pager, participating in multidisciplinary rounds, and furnishing new physicians with a “contacts” card and an orientation guide to help hospitalists write better orders, says Vicki Ising Jue, PharmD.

The personal touch is appreciated. “If I am in the pharmacy making a call and not on the unit, it just makes the phone call so much easier if the caller happens to be someone I’ve worked with before,” says UCSF’s Alan Tan, PharmD.

View hundreds of HM opportunities at SHM's Career Center

The degree of communication with pharmacy services may depend on whether you’re working in a teaching hospital with a structured orientation program or starting out in a community hospital. No matter the setting, though, Gleason says the pharmacist’s mission stays the same.

“We’re all striving to get to the same goal: safe, effective and patient-centered care to achieve positive outcomes for our patients,” she says. “Partnering with pharmacists can really move all of us closer to that goal.”

Gretchen Henkel is a freelance writer based in California. 

You’re ready to discharge a patient, but you don’t know whether the medication you’ve ordered will be available in the outpatient setting. Who do you ask? Your pharmacy service will have the answers, and if you’ve established a collegial relationship with the pharmacists there, most likely you can get a quick answer via page, text, or phone call. But if you don’t have personal contact with your pharmacists, chances are the interchange will impersonal—and that could mean missing ou

“Pharmacists may be underutilized, especially if the range of clinical services they offer are not recognized,” notes Kristine Gleason, RPh, clinical quality leader at Northwestern Memorial Hospital in Chicago. “We can be an excellent resource for young hospitalists and clinicians, offering information on clinical dosing and monitoring of complex, high-risk medications.”

Pharmacists also can be valuable resources for medication reconciliation and patient counseling, Gleason says, adding that “our goal is to work collaboratively with our clinicians to help ensure patients receive evidence-based medication regimens that are safe and without error and that are tailored to each patient’s individualized characteristics.”

Benefits of Rounding

Interactions between hospital pharmacies and HM services vary by institution size and organization. Roberta Barber, PharmD, MPH, is assistant vice president of pharmacy for Virtua Health’s four hospital campuses in New Jersey. At Memorial Hospital, where Erik DeLue, MD, MBA, SFHM, first established a hospitalist program, pharmacists are present in the ICU units and participate in care-coordination rounds.

Barber is crafting policies to extend the decentralized pharmacist model to all of Virtua’s hospitals. Equipped with cordless phones and tablet computers, pharmacists will be able to round with the HM team without sacrificing availability to other physicians and hospital staff. In this way, she says, “physicians will be able to consult with pharmacists as they’re creating their treatment plans, and the pharmacist can intervene regarding potential problem orders right then and there.”

At the University of California at San Francisco Medical Center, clinical pharmacists in the general medicine division work closely with the nine medicine teams run by hospitalists. That means 24/7 availability by pager, participating in multidisciplinary rounds, and furnishing new physicians with a “contacts” card and an orientation guide to help hospitalists write better orders, says Vicki Ising Jue, PharmD.

The personal touch is appreciated. “If I am in the pharmacy making a call and not on the unit, it just makes the phone call so much easier if the caller happens to be someone I’ve worked with before,” says UCSF’s Alan Tan, PharmD.

View hundreds of HM opportunities at SHM's Career Center

The degree of communication with pharmacy services may depend on whether you’re working in a teaching hospital with a structured orientation program or starting out in a community hospital. No matter the setting, though, Gleason says the pharmacist’s mission stays the same.

“We’re all striving to get to the same goal: safe, effective and patient-centered care to achieve positive outcomes for our patients,” she says. “Partnering with pharmacists can really move all of us closer to that goal.”

Gretchen Henkel is a freelance writer based in California. 

You’re ready to discharge a patient, but you don’t know whether the medication you’ve ordered will be available in the outpatient setting. Who do you ask? Your pharmacy service will have the answers, and if you’ve established a collegial relationship with the pharmacists there, most likely you can get a quick answer via page, text, or phone call. But if you don’t have personal contact with your pharmacists, chances are the interchange will impersonal—and that could mean missing ou

“Pharmacists may be underutilized, especially if the range of clinical services they offer are not recognized,” notes Kristine Gleason, RPh, clinical quality leader at Northwestern Memorial Hospital in Chicago. “We can be an excellent resource for young hospitalists and clinicians, offering information on clinical dosing and monitoring of complex, high-risk medications.”

Pharmacists also can be valuable resources for medication reconciliation and patient counseling, Gleason says, adding that “our goal is to work collaboratively with our clinicians to help ensure patients receive evidence-based medication regimens that are safe and without error and that are tailored to each patient’s individualized characteristics.”

Benefits of Rounding

Interactions between hospital pharmacies and HM services vary by institution size and organization. Roberta Barber, PharmD, MPH, is assistant vice president of pharmacy for Virtua Health’s four hospital campuses in New Jersey. At Memorial Hospital, where Erik DeLue, MD, MBA, SFHM, first established a hospitalist program, pharmacists are present in the ICU units and participate in care-coordination rounds.

Barber is crafting policies to extend the decentralized pharmacist model to all of Virtua’s hospitals. Equipped with cordless phones and tablet computers, pharmacists will be able to round with the HM team without sacrificing availability to other physicians and hospital staff. In this way, she says, “physicians will be able to consult with pharmacists as they’re creating their treatment plans, and the pharmacist can intervene regarding potential problem orders right then and there.”

At the University of California at San Francisco Medical Center, clinical pharmacists in the general medicine division work closely with the nine medicine teams run by hospitalists. That means 24/7 availability by pager, participating in multidisciplinary rounds, and furnishing new physicians with a “contacts” card and an orientation guide to help hospitalists write better orders, says Vicki Ising Jue, PharmD.

The personal touch is appreciated. “If I am in the pharmacy making a call and not on the unit, it just makes the phone call so much easier if the caller happens to be someone I’ve worked with before,” says UCSF’s Alan Tan, PharmD.

View hundreds of HM opportunities at SHM's Career Center

The degree of communication with pharmacy services may depend on whether you’re working in a teaching hospital with a structured orientation program or starting out in a community hospital. No matter the setting, though, Gleason says the pharmacist’s mission stays the same.

“We’re all striving to get to the same goal: safe, effective and patient-centered care to achieve positive outcomes for our patients,” she says. “Partnering with pharmacists can really move all of us closer to that goal.”

Gretchen Henkel is a freelance writer based in California. 

PARIS – Impaired physical and cognitive abilities are predictive of worse overall survival in elderly patients with acute myeloid leukemia, according to prospective study findings.

In a 74-patient trial, scores of less than 9 out of 12 on the Short Physical Performance Battery (SPPB) and less than 77 out of 100 on a Modified Mini-Mental State (3MS) exam were associated with a threefold increase in risk of death, compared with scores in patients who had no physical or cognitive difficulties.

The study’s findings could ultimately help determine which elderly patients with acute myeloid leukemia (AML) are fit enough to receive standard chemotherapy regimens for the disease, and which may require a different therapeutic approach. The results should currently be viewed as a "signal" of a possible worse prognosis, however, until further validation.

"Acute leukemia is probably one of the most dramatic examples of age-related outcome disparity in oncology," said study author Dr. Heidi D. Klepin, of Wake Forest University, Winston-Salem, N.C.

"Older patients consistently do much worse when diagnosed with disease than [do] young patients," Dr. Klepin said on Nov. 4 in an interview at the annual meeting of the International Society for Geriatric Oncology (also known as Société Internationale d’Oncologie Gériatrique).

While much research has focused on examining tumor biology in older and younger patients with AML, few studies have looked at differences in the capabilities of the patients themselves, such as increasing vulnerability or frailty in the geriatric population.

"There has been so little done in geriatric assessment in the leukemia population," Dr. Stuart M. Lichtman said in a separate interview.

Dr. Lichtman of Memorial-Sloan–Kettering Cancer Center, N.Y., who was not involved in the study and served as scientific committee chair of the meeting, said the findings were important because they suggest that general and relatively simple-to-measure parameters could provide valuable information to help clinical decision-making. The SPPB includes asking patients to perform a 4-meter timed walk, stand after being in a seated position, and show how well they balance while standing.

The objective of the study was to assess whether performing a geriatric assessment at the patient’s bedside could predict patient’s likely overall survival. All of the patients included in the trial were about to start induction chemotherapy for AML.

The geriatric assessment consisted of multiple tests to examine cognition (3MS), emotion (Center for Epidemiological Studies Depression Scale, Distress Thermometer), self-reported disability (Pepper Assessment Tool for Disability) and objective (SPPB) physical function, grip strength, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI).

The mean age of patients included in the study was 70 years, 56% was male and 78% had an Eastern Cooperative Group Oncology Performance Status (ECOG PS) score of 0-1. The majority (95%) had an intermediate or poor cytogenic profile. The median follow-up was 7.4 months.

At baseline, 30% of patients were identified as having some form of cognitive impairment, 39% had depressive symptoms, 42% were distressed, 41% had reduced instrumental activities of daily living (IADL), 50% had reduced objective physical function, and 42% had comorbidities.

After researchers adjusted for a host of potentially confounding factors, including age, gender, ECOG PS, and cytogenic risk group, among others, hazard ratios for overall survival were 3.4 for SPPB score less than 9 (P =.03) and 3.0 for a 3MS score less than 77 (P = .008).

"There has been so little done in geriatric assessment in the leukemia population."

Reduced self-reported IADL was also associated with worse overall survival (HR, 2.6), but only after adjusting for confounding factors. SPPB and 3MS were also predictive on univariate analysis.

These data suggest that a better assessment of physical function could provide valuable information about a patient’s likely outcome, "even in clinical practice right now," Dr. Klepin said.

"I think we can use this to improve how patients do with standard treatments, by just paying attention [to baseline parameters] and changing how we manage people," she said. "If we are aware of a problem, can we do things that would prevent that problem from putting a patient in the ICU?"

Dr. Klepin also noted that the information provided by the geriatric assessment could be used to inform and to help patents decide whether they want to be treated with standard chemotherapy or perhaps enter into an appropriate clinical trial of novel agents.

Preliminary data from the trial have been published in the Journal of the American Geriatrics Society (2011;59:1837-46).

The study was supported by the American Society of Hematology, Atlantic Philanthropies, the John A. Hartford Association, the Association of Specialty Professors, and the Pepper Center at Wake Forest University. Dr. Klepin and Dr. Lichtman did not report any conflicts of interest.

PARIS – Impaired physical and cognitive abilities are predictive of worse overall survival in elderly patients with acute myeloid leukemia, according to prospective study findings.

In a 74-patient trial, scores of less than 9 out of 12 on the Short Physical Performance Battery (SPPB) and less than 77 out of 100 on a Modified Mini-Mental State (3MS) exam were associated with a threefold increase in risk of death, compared with scores in patients who had no physical or cognitive difficulties.

The study’s findings could ultimately help determine which elderly patients with acute myeloid leukemia (AML) are fit enough to receive standard chemotherapy regimens for the disease, and which may require a different therapeutic approach. The results should currently be viewed as a "signal" of a possible worse prognosis, however, until further validation.

"Acute leukemia is probably one of the most dramatic examples of age-related outcome disparity in oncology," said study author Dr. Heidi D. Klepin, of Wake Forest University, Winston-Salem, N.C.

"Older patients consistently do much worse when diagnosed with disease than [do] young patients," Dr. Klepin said on Nov. 4 in an interview at the annual meeting of the International Society for Geriatric Oncology (also known as Société Internationale d’Oncologie Gériatrique).

While much research has focused on examining tumor biology in older and younger patients with AML, few studies have looked at differences in the capabilities of the patients themselves, such as increasing vulnerability or frailty in the geriatric population.

"There has been so little done in geriatric assessment in the leukemia population," Dr. Stuart M. Lichtman said in a separate interview.

Dr. Lichtman of Memorial-Sloan–Kettering Cancer Center, N.Y., who was not involved in the study and served as scientific committee chair of the meeting, said the findings were important because they suggest that general and relatively simple-to-measure parameters could provide valuable information to help clinical decision-making. The SPPB includes asking patients to perform a 4-meter timed walk, stand after being in a seated position, and show how well they balance while standing.

The objective of the study was to assess whether performing a geriatric assessment at the patient’s bedside could predict patient’s likely overall survival. All of the patients included in the trial were about to start induction chemotherapy for AML.

The geriatric assessment consisted of multiple tests to examine cognition (3MS), emotion (Center for Epidemiological Studies Depression Scale, Distress Thermometer), self-reported disability (Pepper Assessment Tool for Disability) and objective (SPPB) physical function, grip strength, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI).

The mean age of patients included in the study was 70 years, 56% was male and 78% had an Eastern Cooperative Group Oncology Performance Status (ECOG PS) score of 0-1. The majority (95%) had an intermediate or poor cytogenic profile. The median follow-up was 7.4 months.

At baseline, 30% of patients were identified as having some form of cognitive impairment, 39% had depressive symptoms, 42% were distressed, 41% had reduced instrumental activities of daily living (IADL), 50% had reduced objective physical function, and 42% had comorbidities.

After researchers adjusted for a host of potentially confounding factors, including age, gender, ECOG PS, and cytogenic risk group, among others, hazard ratios for overall survival were 3.4 for SPPB score less than 9 (P =.03) and 3.0 for a 3MS score less than 77 (P = .008).

"There has been so little done in geriatric assessment in the leukemia population."

Reduced self-reported IADL was also associated with worse overall survival (HR, 2.6), but only after adjusting for confounding factors. SPPB and 3MS were also predictive on univariate analysis.

These data suggest that a better assessment of physical function could provide valuable information about a patient’s likely outcome, "even in clinical practice right now," Dr. Klepin said.

"I think we can use this to improve how patients do with standard treatments, by just paying attention [to baseline parameters] and changing how we manage people," she said. "If we are aware of a problem, can we do things that would prevent that problem from putting a patient in the ICU?"

Dr. Klepin also noted that the information provided by the geriatric assessment could be used to inform and to help patents decide whether they want to be treated with standard chemotherapy or perhaps enter into an appropriate clinical trial of novel agents.

Preliminary data from the trial have been published in the Journal of the American Geriatrics Society (2011;59:1837-46).

The study was supported by the American Society of Hematology, Atlantic Philanthropies, the John A. Hartford Association, the Association of Specialty Professors, and the Pepper Center at Wake Forest University. Dr. Klepin and Dr. Lichtman did not report any conflicts of interest.

PARIS – Impaired physical and cognitive abilities are predictive of worse overall survival in elderly patients with acute myeloid leukemia, according to prospective study findings.

In a 74-patient trial, scores of less than 9 out of 12 on the Short Physical Performance Battery (SPPB) and less than 77 out of 100 on a Modified Mini-Mental State (3MS) exam were associated with a threefold increase in risk of death, compared with scores in patients who had no physical or cognitive difficulties.

The study’s findings could ultimately help determine which elderly patients with acute myeloid leukemia (AML) are fit enough to receive standard chemotherapy regimens for the disease, and which may require a different therapeutic approach. The results should currently be viewed as a "signal" of a possible worse prognosis, however, until further validation.

"Acute leukemia is probably one of the most dramatic examples of age-related outcome disparity in oncology," said study author Dr. Heidi D. Klepin, of Wake Forest University, Winston-Salem, N.C.

"Older patients consistently do much worse when diagnosed with disease than [do] young patients," Dr. Klepin said on Nov. 4 in an interview at the annual meeting of the International Society for Geriatric Oncology (also known as Société Internationale d’Oncologie Gériatrique).

While much research has focused on examining tumor biology in older and younger patients with AML, few studies have looked at differences in the capabilities of the patients themselves, such as increasing vulnerability or frailty in the geriatric population.

"There has been so little done in geriatric assessment in the leukemia population," Dr. Stuart M. Lichtman said in a separate interview.

Dr. Lichtman of Memorial-Sloan–Kettering Cancer Center, N.Y., who was not involved in the study and served as scientific committee chair of the meeting, said the findings were important because they suggest that general and relatively simple-to-measure parameters could provide valuable information to help clinical decision-making. The SPPB includes asking patients to perform a 4-meter timed walk, stand after being in a seated position, and show how well they balance while standing.

The objective of the study was to assess whether performing a geriatric assessment at the patient’s bedside could predict patient’s likely overall survival. All of the patients included in the trial were about to start induction chemotherapy for AML.

The geriatric assessment consisted of multiple tests to examine cognition (3MS), emotion (Center for Epidemiological Studies Depression Scale, Distress Thermometer), self-reported disability (Pepper Assessment Tool for Disability) and objective (SPPB) physical function, grip strength, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI).

The mean age of patients included in the study was 70 years, 56% was male and 78% had an Eastern Cooperative Group Oncology Performance Status (ECOG PS) score of 0-1. The majority (95%) had an intermediate or poor cytogenic profile. The median follow-up was 7.4 months.

At baseline, 30% of patients were identified as having some form of cognitive impairment, 39% had depressive symptoms, 42% were distressed, 41% had reduced instrumental activities of daily living (IADL), 50% had reduced objective physical function, and 42% had comorbidities.

After researchers adjusted for a host of potentially confounding factors, including age, gender, ECOG PS, and cytogenic risk group, among others, hazard ratios for overall survival were 3.4 for SPPB score less than 9 (P =.03) and 3.0 for a 3MS score less than 77 (P = .008).

"There has been so little done in geriatric assessment in the leukemia population."

Reduced self-reported IADL was also associated with worse overall survival (HR, 2.6), but only after adjusting for confounding factors. SPPB and 3MS were also predictive on univariate analysis.

These data suggest that a better assessment of physical function could provide valuable information about a patient’s likely outcome, "even in clinical practice right now," Dr. Klepin said.

"I think we can use this to improve how patients do with standard treatments, by just paying attention [to baseline parameters] and changing how we manage people," she said. "If we are aware of a problem, can we do things that would prevent that problem from putting a patient in the ICU?"

Dr. Klepin also noted that the information provided by the geriatric assessment could be used to inform and to help patents decide whether they want to be treated with standard chemotherapy or perhaps enter into an appropriate clinical trial of novel agents.

Preliminary data from the trial have been published in the Journal of the American Geriatrics Society (2011;59:1837-46).

The study was supported by the American Society of Hematology, Atlantic Philanthropies, the John A. Hartford Association, the Association of Specialty Professors, and the Pepper Center at Wake Forest University. Dr. Klepin and Dr. Lichtman did not report any conflicts of interest.

A recent report (PDF) from The Commonwealth Fund that suggests the quality and efficacy of the U.S. healthcare system has remained relatively static in the past three years has bright spots for HM, an academic hospitalist says.

Kedar Mate, MD, assistant professor of medicine with the division of hospital medicine at Weill Cornell Medical School in New York City, says the report, which was compiled before any of the facets of the Affordable Care Act were implemented, helps argue why hospitalists are poised to take the reins of those needed quality reforms.

"They're the natural leaders of this work moving forward from the physician perspective," says Dr. Mate, a faculty member at the Institute for Healthcare Improvement in Cambridge, Mass. "They have a strong role to play in shepherding and championing and really being the arms and legs of the quality and safety movement, in many ways. Not only leading it, but actually executing it."

The report released last month, "Why Not the Best? Results from the National Scorecard on U.S. Health System Performance, 2011," measures 42 indicators of healthcare quality, access, efficiency, equity, and healthy lives. In overall terms, the U.S. score has varied only slightly in the third national scorecard. And while the report cautions that year-to-year analyses of quality measures are not directly comparable because of changing categories, Dr. Mate notes there have been significant improvements in areas that HM and health system improvement efforts have targeted.

The study, for example, reports half of adults with high blood pressure had the condition under control in 2007-2008, up from 31% in 1999-2000. The data also show that the rate of controlled blood sugar levels in adults with diabetes ticked up to 86% in 2007-2008 from 79% in 1999-2000.

"Where we turn our attention, particularly with focused quality initiatives, we're seeing some measurable change," Dr. Mate says. "There's absolutely value in identifying and knowing where we are seeing benefits, because those ought to be built upon."

A recent report (PDF) from The Commonwealth Fund that suggests the quality and efficacy of the U.S. healthcare system has remained relatively static in the past three years has bright spots for HM, an academic hospitalist says.

Kedar Mate, MD, assistant professor of medicine with the division of hospital medicine at Weill Cornell Medical School in New York City, says the report, which was compiled before any of the facets of the Affordable Care Act were implemented, helps argue why hospitalists are poised to take the reins of those needed quality reforms.

"They're the natural leaders of this work moving forward from the physician perspective," says Dr. Mate, a faculty member at the Institute for Healthcare Improvement in Cambridge, Mass. "They have a strong role to play in shepherding and championing and really being the arms and legs of the quality and safety movement, in many ways. Not only leading it, but actually executing it."

The report released last month, "Why Not the Best? Results from the National Scorecard on U.S. Health System Performance, 2011," measures 42 indicators of healthcare quality, access, efficiency, equity, and healthy lives. In overall terms, the U.S. score has varied only slightly in the third national scorecard. And while the report cautions that year-to-year analyses of quality measures are not directly comparable because of changing categories, Dr. Mate notes there have been significant improvements in areas that HM and health system improvement efforts have targeted.

The study, for example, reports half of adults with high blood pressure had the condition under control in 2007-2008, up from 31% in 1999-2000. The data also show that the rate of controlled blood sugar levels in adults with diabetes ticked up to 86% in 2007-2008 from 79% in 1999-2000.

"Where we turn our attention, particularly with focused quality initiatives, we're seeing some measurable change," Dr. Mate says. "There's absolutely value in identifying and knowing where we are seeing benefits, because those ought to be built upon."

A recent report (PDF) from The Commonwealth Fund that suggests the quality and efficacy of the U.S. healthcare system has remained relatively static in the past three years has bright spots for HM, an academic hospitalist says.

Kedar Mate, MD, assistant professor of medicine with the division of hospital medicine at Weill Cornell Medical School in New York City, says the report, which was compiled before any of the facets of the Affordable Care Act were implemented, helps argue why hospitalists are poised to take the reins of those needed quality reforms.

"They're the natural leaders of this work moving forward from the physician perspective," says Dr. Mate, a faculty member at the Institute for Healthcare Improvement in Cambridge, Mass. "They have a strong role to play in shepherding and championing and really being the arms and legs of the quality and safety movement, in many ways. Not only leading it, but actually executing it."

The report released last month, "Why Not the Best? Results from the National Scorecard on U.S. Health System Performance, 2011," measures 42 indicators of healthcare quality, access, efficiency, equity, and healthy lives. In overall terms, the U.S. score has varied only slightly in the third national scorecard. And while the report cautions that year-to-year analyses of quality measures are not directly comparable because of changing categories, Dr. Mate notes there have been significant improvements in areas that HM and health system improvement efforts have targeted.

The study, for example, reports half of adults with high blood pressure had the condition under control in 2007-2008, up from 31% in 1999-2000. The data also show that the rate of controlled blood sugar levels in adults with diabetes ticked up to 86% in 2007-2008 from 79% in 1999-2000.

"Where we turn our attention, particularly with focused quality initiatives, we're seeing some measurable change," Dr. Mate says. "There's absolutely value in identifying and knowing where we are seeing benefits, because those ought to be built upon."

A partnership with nearly 400 local churches is helping the seven-hospital Methodist Le Bonheur Healthcare System, based in Memphis, Tenn., return hospitalized patients to their communities with the support they need to manage such chronic conditions as congestive heart failure.

Preliminary research into the Congregational Health Network shows a 20% decrease in readmissions by participating patients, compared with matched controls, says Teresa Cutts, PhD, director of research for innovation for Methodist's Center of Excellence in Faith & Health.

But the program is more than just "outreach" from the health system to the churches, she adds. It also is "in-reach" from community partners to the health system and a true collaboration. "The clergy have a covenant; they have deep ownership of this network," she says.

Trained volunteer liaisons at each participating church are the bridge to the health system. Patients who are members of the network and who opt in at admission are connected to liaisons or other church volunteers, who then visit patients in the hospital and at their homes following discharge. Hospital-employed community care workers (called navigators) help coordinate these connections, supported by Methodist's electronic health record (EHR).

The network has 12,000 registered members. Approximately 1,100 volunteers have received training in such subjects as hospital visitation, hands-on aftercare, and mental health first aid. Larger goals, Dr. Cutts says, include pushing this support further upstream into preventive care, documenting outcomes, and incorporating more clinical issues into the volunteer training.

"We think it's time, and will really empower people," she says.

In September, health system representatives visited the White House to share the coalition's success story. For more information, contact Cutts at [email protected].

A partnership with nearly 400 local churches is helping the seven-hospital Methodist Le Bonheur Healthcare System, based in Memphis, Tenn., return hospitalized patients to their communities with the support they need to manage such chronic conditions as congestive heart failure.

Preliminary research into the Congregational Health Network shows a 20% decrease in readmissions by participating patients, compared with matched controls, says Teresa Cutts, PhD, director of research for innovation for Methodist's Center of Excellence in Faith & Health.

But the program is more than just "outreach" from the health system to the churches, she adds. It also is "in-reach" from community partners to the health system and a true collaboration. "The clergy have a covenant; they have deep ownership of this network," she says.

Trained volunteer liaisons at each participating church are the bridge to the health system. Patients who are members of the network and who opt in at admission are connected to liaisons or other church volunteers, who then visit patients in the hospital and at their homes following discharge. Hospital-employed community care workers (called navigators) help coordinate these connections, supported by Methodist's electronic health record (EHR).

The network has 12,000 registered members. Approximately 1,100 volunteers have received training in such subjects as hospital visitation, hands-on aftercare, and mental health first aid. Larger goals, Dr. Cutts says, include pushing this support further upstream into preventive care, documenting outcomes, and incorporating more clinical issues into the volunteer training.

"We think it's time, and will really empower people," she says.

In September, health system representatives visited the White House to share the coalition's success story. For more information, contact Cutts at [email protected].

A partnership with nearly 400 local churches is helping the seven-hospital Methodist Le Bonheur Healthcare System, based in Memphis, Tenn., return hospitalized patients to their communities with the support they need to manage such chronic conditions as congestive heart failure.

Preliminary research into the Congregational Health Network shows a 20% decrease in readmissions by participating patients, compared with matched controls, says Teresa Cutts, PhD, director of research for innovation for Methodist's Center of Excellence in Faith & Health.

But the program is more than just "outreach" from the health system to the churches, she adds. It also is "in-reach" from community partners to the health system and a true collaboration. "The clergy have a covenant; they have deep ownership of this network," she says.

Trained volunteer liaisons at each participating church are the bridge to the health system. Patients who are members of the network and who opt in at admission are connected to liaisons or other church volunteers, who then visit patients in the hospital and at their homes following discharge. Hospital-employed community care workers (called navigators) help coordinate these connections, supported by Methodist's electronic health record (EHR).

The network has 12,000 registered members. Approximately 1,100 volunteers have received training in such subjects as hospital visitation, hands-on aftercare, and mental health first aid. Larger goals, Dr. Cutts says, include pushing this support further upstream into preventive care, documenting outcomes, and incorporating more clinical issues into the volunteer training.

"We think it's time, and will really empower people," she says.

In September, health system representatives visited the White House to share the coalition's success story. For more information, contact Cutts at [email protected].

Treatment with fenofibric acid "may not" lower the risk of myocardial infarction or stroke in patients treated with the cholesterol-lowering medication, information that is being added to the drug’s label, the Food and Drug Administration announced on Nov. 9.

The FDA statement and decision to make the labeling change are based on the agency’s review of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, which showed no significant differences in the risk of major adverse cardiac events between patients treated with fenofibrate and simvastatin and those treated with simvastatin alone.

Data from the ACCORD lipid trial have been added to the drug label’s "Important Limitations of Use" and "Warnings and Precautions" sections, and to the medication guide given to patients with each prescription.

"Health care professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug to patients," the FDA cautioned in its statement, and physicians should encourage their patients to read the medication guide.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee earlier this year, the panel was divided over how the ACCORD lipid results should affect the drugs labeling and the approved indication for use with a statin. Of the 13 panel members, 6 agreed that the main findings of ACCORD should be added to the drug’s label, while 4 said that the co-administration indication should be withdrawn. The remaining three panelists said that marketing should continue with no label changes.

Fenofibric acid, a peroxisome proliferator receptor-alpha activator marketed as Trilipix by Abbott Laboratories, was approved in 2008, for use with a statin to reduce triglycerides and increase HDL cholesterol in patients with mixed dyslipidemia and coronary heart disease or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL cholesterol goal. It is also indicated as monotherapy to reduce triglycerides in patients with severe hypertriglyceridemia; as monotherapy to reduce elevated LDL cholesterol levels, total-C cholesterol, triglycerides, and apolipoprotein-B, and to increase HDL cholesterol levels in patients with primary hyperlipidemia or mixed dyslipidemia.

In the ACCORD lipid study, patients were treated with simvastatin for 4 weeks and were then randomized to continue treatment with simvastatin and placebo (2,753 patients) or simvastatin and fenofibrate (2,765 patients).

Over a mean follow-up of 4.7 years, the risk of major adverse cardiovascular events (nonfatal MI, nonfatal stroke, and death from cardiovascular disease) was 8% lower among patients on the combination, but the difference was not statistically significant. Among men, the risk was reduced by 18% among those on the combination, compared with those on simvastatin alone.

Among women, however, the risk of major adverse cardiovascular events was 38% greater among those on the combination, compared with those on placebo.

That gender effect was not seen in another large randomized controlled clinical trial comparing fenofibrate to placebo, so "the clinical significance of this subgroup finding is unclear," the FDA statement noted.

But "the study results also raised the hypothesis that a subgroup of patients with high triglycerides and low high-density lipoprotein cholesterol may experience some reduction in the risk of MACE [major adverse cardiovascular events] from the combination therapy vs. simvastatin monotherapy," the agency noted.

The FDA will require Abbott to conduct a randomized, double-blind, placebo-controlled clinical trial to evaluate whether combination treatment with fenofibrate plus a statin significantly reduces the rate of MACE in men and women who are at their LDL cholesterol goal on statin therapy but have residually high triglycerides and low HDL cholesterol.

Serious adverse events associated with Trilipix should be reported to the FDA’s MedWatch program online or at 800-332-1088.

Treatment with fenofibric acid "may not" lower the risk of myocardial infarction or stroke in patients treated with the cholesterol-lowering medication, information that is being added to the drug’s label, the Food and Drug Administration announced on Nov. 9.

The FDA statement and decision to make the labeling change are based on the agency’s review of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, which showed no significant differences in the risk of major adverse cardiac events between patients treated with fenofibrate and simvastatin and those treated with simvastatin alone.

Data from the ACCORD lipid trial have been added to the drug label’s "Important Limitations of Use" and "Warnings and Precautions" sections, and to the medication guide given to patients with each prescription.

"Health care professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug to patients," the FDA cautioned in its statement, and physicians should encourage their patients to read the medication guide.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee earlier this year, the panel was divided over how the ACCORD lipid results should affect the drugs labeling and the approved indication for use with a statin. Of the 13 panel members, 6 agreed that the main findings of ACCORD should be added to the drug’s label, while 4 said that the co-administration indication should be withdrawn. The remaining three panelists said that marketing should continue with no label changes.

Fenofibric acid, a peroxisome proliferator receptor-alpha activator marketed as Trilipix by Abbott Laboratories, was approved in 2008, for use with a statin to reduce triglycerides and increase HDL cholesterol in patients with mixed dyslipidemia and coronary heart disease or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL cholesterol goal. It is also indicated as monotherapy to reduce triglycerides in patients with severe hypertriglyceridemia; as monotherapy to reduce elevated LDL cholesterol levels, total-C cholesterol, triglycerides, and apolipoprotein-B, and to increase HDL cholesterol levels in patients with primary hyperlipidemia or mixed dyslipidemia.

In the ACCORD lipid study, patients were treated with simvastatin for 4 weeks and were then randomized to continue treatment with simvastatin and placebo (2,753 patients) or simvastatin and fenofibrate (2,765 patients).

Over a mean follow-up of 4.7 years, the risk of major adverse cardiovascular events (nonfatal MI, nonfatal stroke, and death from cardiovascular disease) was 8% lower among patients on the combination, but the difference was not statistically significant. Among men, the risk was reduced by 18% among those on the combination, compared with those on simvastatin alone.

Among women, however, the risk of major adverse cardiovascular events was 38% greater among those on the combination, compared with those on placebo.

That gender effect was not seen in another large randomized controlled clinical trial comparing fenofibrate to placebo, so "the clinical significance of this subgroup finding is unclear," the FDA statement noted.

But "the study results also raised the hypothesis that a subgroup of patients with high triglycerides and low high-density lipoprotein cholesterol may experience some reduction in the risk of MACE [major adverse cardiovascular events] from the combination therapy vs. simvastatin monotherapy," the agency noted.

The FDA will require Abbott to conduct a randomized, double-blind, placebo-controlled clinical trial to evaluate whether combination treatment with fenofibrate plus a statin significantly reduces the rate of MACE in men and women who are at their LDL cholesterol goal on statin therapy but have residually high triglycerides and low HDL cholesterol.

Serious adverse events associated with Trilipix should be reported to the FDA’s MedWatch program online or at 800-332-1088.

Treatment with fenofibric acid "may not" lower the risk of myocardial infarction or stroke in patients treated with the cholesterol-lowering medication, information that is being added to the drug’s label, the Food and Drug Administration announced on Nov. 9.

The FDA statement and decision to make the labeling change are based on the agency’s review of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, which showed no significant differences in the risk of major adverse cardiac events between patients treated with fenofibrate and simvastatin and those treated with simvastatin alone.

Data from the ACCORD lipid trial have been added to the drug label’s "Important Limitations of Use" and "Warnings and Precautions" sections, and to the medication guide given to patients with each prescription.

"Health care professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug to patients," the FDA cautioned in its statement, and physicians should encourage their patients to read the medication guide.

At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee earlier this year, the panel was divided over how the ACCORD lipid results should affect the drugs labeling and the approved indication for use with a statin. Of the 13 panel members, 6 agreed that the main findings of ACCORD should be added to the drug’s label, while 4 said that the co-administration indication should be withdrawn. The remaining three panelists said that marketing should continue with no label changes.

Fenofibric acid, a peroxisome proliferator receptor-alpha activator marketed as Trilipix by Abbott Laboratories, was approved in 2008, for use with a statin to reduce triglycerides and increase HDL cholesterol in patients with mixed dyslipidemia and coronary heart disease or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL cholesterol goal. It is also indicated as monotherapy to reduce triglycerides in patients with severe hypertriglyceridemia; as monotherapy to reduce elevated LDL cholesterol levels, total-C cholesterol, triglycerides, and apolipoprotein-B, and to increase HDL cholesterol levels in patients with primary hyperlipidemia or mixed dyslipidemia.

In the ACCORD lipid study, patients were treated with simvastatin for 4 weeks and were then randomized to continue treatment with simvastatin and placebo (2,753 patients) or simvastatin and fenofibrate (2,765 patients).

Over a mean follow-up of 4.7 years, the risk of major adverse cardiovascular events (nonfatal MI, nonfatal stroke, and death from cardiovascular disease) was 8% lower among patients on the combination, but the difference was not statistically significant. Among men, the risk was reduced by 18% among those on the combination, compared with those on simvastatin alone.

Among women, however, the risk of major adverse cardiovascular events was 38% greater among those on the combination, compared with those on placebo.

That gender effect was not seen in another large randomized controlled clinical trial comparing fenofibrate to placebo, so "the clinical significance of this subgroup finding is unclear," the FDA statement noted.

But "the study results also raised the hypothesis that a subgroup of patients with high triglycerides and low high-density lipoprotein cholesterol may experience some reduction in the risk of MACE [major adverse cardiovascular events] from the combination therapy vs. simvastatin monotherapy," the agency noted.

The FDA will require Abbott to conduct a randomized, double-blind, placebo-controlled clinical trial to evaluate whether combination treatment with fenofibrate plus a statin significantly reduces the rate of MACE in men and women who are at their LDL cholesterol goal on statin therapy but have residually high triglycerides and low HDL cholesterol.

Serious adverse events associated with Trilipix should be reported to the FDA’s MedWatch program online or at 800-332-1088.

Overuse injuries are very common in children and teenagers, especially among kids who play sports throughout the year.

Although rare, primary systemic vasculitis in children is associated with significant mortality and morbidity when not properly treated. Optimal management of the group of multiorgan inflammatory conditions is hampered by the lack of evidence-based therapies. This shortage of data has been attributed, in part, to the absence of a standardized outcome measure for use in clinical trials, according to Dr. Pavla Dolezalova.

"Until recently, no standardized vasculitis activity assessment tool has been available for children, so some pediatric studies apply adult measures, such as the Birmingham Vasculitis Activity Score [BVAS]," she said. Further, although nonspecific inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein can reflect systemic vasculitis disease activity, they do not distinguish it from infectious complications. Use of the global assessment of disease activity by the treating physician using the visual analog scale is of limited utility in clinical trials, she noted.

In an effort to facilitate more informative clinical trials of primary systemic vasculitis in children, Dr. Dolezalova of Charles University and General University Hospital in Prague, Czech Republic, and her colleagues have developed a quantitative clinical index of manifestations of active disease, called the Pediatric Vasculitis Activity Score (PVAS), which has been preliminarily validated as a useful clinical measure with good interobserver reliability (Pediatr. Rheumatol. Online J. 2011 [doi:10.1186/1546-0096-9-S1-P92]).

In this column, Dr. Dolezalova describes the need for the assessment tool as well as some of the development challenges.

Question: Why are outcome assessment tools used for adults with systemic vasculitis not ideal for measuring disease activity in children?

Dr. Dolezalova: Tools used in adults are not fully applicable in children for multiple reasons. Disease presentations and outcome of primary systemic vasculitides appear to be different in children. Among the most obvious differences between adult and pediatric variants of the disease are the developmental and growth aspects; differences in functional, educational, and social impacts of longstanding disease; different drug pharmacokinetics and toxicity profiles; and the absence of comorbidities in children.

Question: What specific features have been incorporated into the PVAS?

Dr. Dolezalova: The development of the pediatric-specific tool has been a result of an international collaborative effort of pediatric rheumatologists from the vasculitis working groups of PReS (Pediatric Rheumatology European Society) and CARRA (North American Childhood Arthritis & Rheumatology Research Alliance), with the help of the European Vasculitis Study Group (EUVAS). We adapted the Birmingham Vasculitis Activity Score (BVAS 2003), the most commonly used tool in adult vasculitis patients, into PVAS. It is a systematic clinical scoring system that identifies selected features of active vasculitis in nine organ systems. Based on the analysis of the most common systemic vasculitis presentations in children reported to the PReS/PRINTO (Pediatric Rheumatology International Trials Organization) vasculitis registry, eight pediatric-relevant items and their definitions were added to the original BVAS 2003 in the cutaneous, cardiovascular, and abdominal systems. Additionally, by consensus, the maximum score for each organ system was to remain unchanged to facilitate longitudinal congruity with the BVAS. Among the 56 BVAS 2003 items, we redefined 22 for pediatric use.

Question: What were some of the challenges involved in the development of this tool?

Dr. Dolezalova: At the beginning of the process, we had to decide which principal way to follow: whether to start developing a brand new, originally pediatric tool, or to explore the applicability of existing measures and rely on the expertise of our adult rheumatology colleagues. Having gone for the second option meant that we had to accept existing adult concepts of vasculitis activity and damage assessments. The next challenge we had to overcome was that of modifying definitions of individual disease signs and symptoms from the BVAS glossary to be appropriate for pediatric patients. We wanted them to remain compatible with their adult counterparts but also to reflect pediatric reality. Learning the training process of vasculitis activity assessment and undergoing it according to the principles set up by EUVAS had been a true challenge for all pediatricians involved in the PVAS development.

Question: How is the PVAS tool being validated?

Dr. Dolezalova: The PVAS validation has been a multistep process that is now in its final stage. During consensus meetings, content and face validity were established, resulting in minor modifications to the PVAS and its glossary. Scoring of the pediatric paper cases during the training process provided information on the tool’s feasibility. Prospective real-patient assessment, including duplicate assessments by two trained researchers and follow-up evaluation in newly diagnosed or relapsing patients, provided data on the tool’s reliability, responsiveness, and discriminative ability. Currently, analysis of the prospective multicenter data on the larger patient cohort is ongoing.

Interview by Diana Mahoney

Dr. Dolezalova is the national co-coordinator of PRINTO and chairperson of the PReS clinical affairs committee. She had no relevant financial disclosures.

Overuse injuries are very common in children and teenagers, especially among kids who play sports throughout the year.

Although rare, primary systemic vasculitis in children is associated with significant mortality and morbidity when not properly treated. Optimal management of the group of multiorgan inflammatory conditions is hampered by the lack of evidence-based therapies. This shortage of data has been attributed, in part, to the absence of a standardized outcome measure for use in clinical trials, according to Dr. Pavla Dolezalova.

"Until recently, no standardized vasculitis activity assessment tool has been available for children, so some pediatric studies apply adult measures, such as the Birmingham Vasculitis Activity Score [BVAS]," she said. Further, although nonspecific inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein can reflect systemic vasculitis disease activity, they do not distinguish it from infectious complications. Use of the global assessment of disease activity by the treating physician using the visual analog scale is of limited utility in clinical trials, she noted.

In an effort to facilitate more informative clinical trials of primary systemic vasculitis in children, Dr. Dolezalova of Charles University and General University Hospital in Prague, Czech Republic, and her colleagues have developed a quantitative clinical index of manifestations of active disease, called the Pediatric Vasculitis Activity Score (PVAS), which has been preliminarily validated as a useful clinical measure with good interobserver reliability (Pediatr. Rheumatol. Online J. 2011 [doi:10.1186/1546-0096-9-S1-P92]).

In this column, Dr. Dolezalova describes the need for the assessment tool as well as some of the development challenges.

Question: Why are outcome assessment tools used for adults with systemic vasculitis not ideal for measuring disease activity in children?

Dr. Dolezalova: Tools used in adults are not fully applicable in children for multiple reasons. Disease presentations and outcome of primary systemic vasculitides appear to be different in children. Among the most obvious differences between adult and pediatric variants of the disease are the developmental and growth aspects; differences in functional, educational, and social impacts of longstanding disease; different drug pharmacokinetics and toxicity profiles; and the absence of comorbidities in children.

Question: What specific features have been incorporated into the PVAS?

Dr. Dolezalova: The development of the pediatric-specific tool has been a result of an international collaborative effort of pediatric rheumatologists from the vasculitis working groups of PReS (Pediatric Rheumatology European Society) and CARRA (North American Childhood Arthritis & Rheumatology Research Alliance), with the help of the European Vasculitis Study Group (EUVAS). We adapted the Birmingham Vasculitis Activity Score (BVAS 2003), the most commonly used tool in adult vasculitis patients, into PVAS. It is a systematic clinical scoring system that identifies selected features of active vasculitis in nine organ systems. Based on the analysis of the most common systemic vasculitis presentations in children reported to the PReS/PRINTO (Pediatric Rheumatology International Trials Organization) vasculitis registry, eight pediatric-relevant items and their definitions were added to the original BVAS 2003 in the cutaneous, cardiovascular, and abdominal systems. Additionally, by consensus, the maximum score for each organ system was to remain unchanged to facilitate longitudinal congruity with the BVAS. Among the 56 BVAS 2003 items, we redefined 22 for pediatric use.

Question: What were some of the challenges involved in the development of this tool?

Dr. Dolezalova: At the beginning of the process, we had to decide which principal way to follow: whether to start developing a brand new, originally pediatric tool, or to explore the applicability of existing measures and rely on the expertise of our adult rheumatology colleagues. Having gone for the second option meant that we had to accept existing adult concepts of vasculitis activity and damage assessments. The next challenge we had to overcome was that of modifying definitions of individual disease signs and symptoms from the BVAS glossary to be appropriate for pediatric patients. We wanted them to remain compatible with their adult counterparts but also to reflect pediatric reality. Learning the training process of vasculitis activity assessment and undergoing it according to the principles set up by EUVAS had been a true challenge for all pediatricians involved in the PVAS development.

Question: How is the PVAS tool being validated?

Dr. Dolezalova: The PVAS validation has been a multistep process that is now in its final stage. During consensus meetings, content and face validity were established, resulting in minor modifications to the PVAS and its glossary. Scoring of the pediatric paper cases during the training process provided information on the tool’s feasibility. Prospective real-patient assessment, including duplicate assessments by two trained researchers and follow-up evaluation in newly diagnosed or relapsing patients, provided data on the tool’s reliability, responsiveness, and discriminative ability. Currently, analysis of the prospective multicenter data on the larger patient cohort is ongoing.

Interview by Diana Mahoney

Dr. Dolezalova is the national co-coordinator of PRINTO and chairperson of the PReS clinical affairs committee. She had no relevant financial disclosures.

Overuse injuries are very common in children and teenagers, especially among kids who play sports throughout the year.

Although rare, primary systemic vasculitis in children is associated with significant mortality and morbidity when not properly treated. Optimal management of the group of multiorgan inflammatory conditions is hampered by the lack of evidence-based therapies. This shortage of data has been attributed, in part, to the absence of a standardized outcome measure for use in clinical trials, according to Dr. Pavla Dolezalova.

"Until recently, no standardized vasculitis activity assessment tool has been available for children, so some pediatric studies apply adult measures, such as the Birmingham Vasculitis Activity Score [BVAS]," she said. Further, although nonspecific inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein can reflect systemic vasculitis disease activity, they do not distinguish it from infectious complications. Use of the global assessment of disease activity by the treating physician using the visual analog scale is of limited utility in clinical trials, she noted.

In an effort to facilitate more informative clinical trials of primary systemic vasculitis in children, Dr. Dolezalova of Charles University and General University Hospital in Prague, Czech Republic, and her colleagues have developed a quantitative clinical index of manifestations of active disease, called the Pediatric Vasculitis Activity Score (PVAS), which has been preliminarily validated as a useful clinical measure with good interobserver reliability (Pediatr. Rheumatol. Online J. 2011 [doi:10.1186/1546-0096-9-S1-P92]).

In this column, Dr. Dolezalova describes the need for the assessment tool as well as some of the development challenges.

Question: Why are outcome assessment tools used for adults with systemic vasculitis not ideal for measuring disease activity in children?

Dr. Dolezalova: Tools used in adults are not fully applicable in children for multiple reasons. Disease presentations and outcome of primary systemic vasculitides appear to be different in children. Among the most obvious differences between adult and pediatric variants of the disease are the developmental and growth aspects; differences in functional, educational, and social impacts of longstanding disease; different drug pharmacokinetics and toxicity profiles; and the absence of comorbidities in children.

Question: What specific features have been incorporated into the PVAS?

Dr. Dolezalova: The development of the pediatric-specific tool has been a result of an international collaborative effort of pediatric rheumatologists from the vasculitis working groups of PReS (Pediatric Rheumatology European Society) and CARRA (North American Childhood Arthritis & Rheumatology Research Alliance), with the help of the European Vasculitis Study Group (EUVAS). We adapted the Birmingham Vasculitis Activity Score (BVAS 2003), the most commonly used tool in adult vasculitis patients, into PVAS. It is a systematic clinical scoring system that identifies selected features of active vasculitis in nine organ systems. Based on the analysis of the most common systemic vasculitis presentations in children reported to the PReS/PRINTO (Pediatric Rheumatology International Trials Organization) vasculitis registry, eight pediatric-relevant items and their definitions were added to the original BVAS 2003 in the cutaneous, cardiovascular, and abdominal systems. Additionally, by consensus, the maximum score for each organ system was to remain unchanged to facilitate longitudinal congruity with the BVAS. Among the 56 BVAS 2003 items, we redefined 22 for pediatric use.

Question: What were some of the challenges involved in the development of this tool?

Dr. Dolezalova: At the beginning of the process, we had to decide which principal way to follow: whether to start developing a brand new, originally pediatric tool, or to explore the applicability of existing measures and rely on the expertise of our adult rheumatology colleagues. Having gone for the second option meant that we had to accept existing adult concepts of vasculitis activity and damage assessments. The next challenge we had to overcome was that of modifying definitions of individual disease signs and symptoms from the BVAS glossary to be appropriate for pediatric patients. We wanted them to remain compatible with their adult counterparts but also to reflect pediatric reality. Learning the training process of vasculitis activity assessment and undergoing it according to the principles set up by EUVAS had been a true challenge for all pediatricians involved in the PVAS development.

Question: How is the PVAS tool being validated?

Dr. Dolezalova: The PVAS validation has been a multistep process that is now in its final stage. During consensus meetings, content and face validity were established, resulting in minor modifications to the PVAS and its glossary. Scoring of the pediatric paper cases during the training process provided information on the tool’s feasibility. Prospective real-patient assessment, including duplicate assessments by two trained researchers and follow-up evaluation in newly diagnosed or relapsing patients, provided data on the tool’s reliability, responsiveness, and discriminative ability. Currently, analysis of the prospective multicenter data on the larger patient cohort is ongoing.

Interview by Diana Mahoney

Dr. Dolezalova is the national co-coordinator of PRINTO and chairperson of the PReS clinical affairs committee. She had no relevant financial disclosures.