The development of biosimilars such as etanercept SB4 offers a “significant opportunity to decrease medical care cost and increase treatment options,” Alessandro Giunta, MD, of the department of dermatology at the University of Rome Tor Vergata, and associates reported in a letter to the editor in the British Journal of Dermatology.

Dr. Giunta and his associates performed an observational, retrospective, single-center study to investigate etanercept biosimilar SB4 in patients being treated for plaque type psoriasis and psoriatic arthritis (PsA). They evaluated 40 patients – 21 men and 19 women – mean age 55, ranging from 19 to 79 years. The patients received the etanercept biosimilar SB4 between Oct. 21, 2016, and March 31, 2017, at University of Rome Tor Vergata’s department of dermatology. (The etanercept biosimilar SB4 was approved April 29 by the Food and Drug Administration under the brand name Eticovo [etanercept-ykro]. It is also approved in other countries under the names Benepali and Brenzys.)

Accounting for erythrocyte sedimentation rate as a variable, Dr. Giunta and colleagues calculated disease activity scores based on 28 joints; 14 patients (35%) had plaque psoriasis (mean Psoriasis Area Severity Index [PASI] of 9.61 at baseline), while 26 (65%) had psoriatic arthritis (mean PASI, 4.69). All patients reported prior treatment with systemic conventional and biologic treatments. A group of 10 patients (25%) who had been previously treated with etanercept originator underwent an intermittent treatment regimen of 24 weeks with etanercept biosimilar, which was interrupted once clinical resolution was achieved. No treatments were prescribed between etanercept originator and etanercept biosimilar. Mean exposure was 50.4 weeks, ranging from 24 to 96 weeks, with an average washout period of 12.1 weeks from originator to biosimilar (range 8-24).

A significant improvement in mean PASI score was observed in plaque type psoriasis patients as well as psoriatic arthritis patients at week 24 (P less than .0001 and P less than .001, respectively), noted Dr. Giunta and associates.

“All scores achieved a statistical significant improvement with the exception of [swollen joint count] that markedly improved but not significantly,” they added. One patient experienced injection site reaction, but no serious adverse events were observed.

Despite low sample size and limited follow-up time, the authors concluded that etanercept biosimilar achieved effectiveness as a treatment for psoriatic patients even in cases involving previous exposure to originator etanercept. Cost savings of 61.58% for 50-mg treatment and 62.55% for 25-mg treatment respectively guaranteed “the continuity of etanercept-treated patients’ care and gave us the opportunity to allocate patients in innovative but more expensive agents with marginal increase in our annual budget,” they noted.

The authors reported serving as consultants and speakers for AbbVie, Biogen, Eli Lilly, Janssen, Pfizer, and Novartis.

SOURCE: Giunta A et al. Br J Dermatol. 2019 May 3. doi: 10.1111/bjd.18090.

The development of biosimilars such as etanercept SB4 offers a “significant opportunity to decrease medical care cost and increase treatment options,” Alessandro Giunta, MD, of the department of dermatology at the University of Rome Tor Vergata, and associates reported in a letter to the editor in the British Journal of Dermatology.

Dr. Giunta and his associates performed an observational, retrospective, single-center study to investigate etanercept biosimilar SB4 in patients being treated for plaque type psoriasis and psoriatic arthritis (PsA). They evaluated 40 patients – 21 men and 19 women – mean age 55, ranging from 19 to 79 years. The patients received the etanercept biosimilar SB4 between Oct. 21, 2016, and March 31, 2017, at University of Rome Tor Vergata’s department of dermatology. (The etanercept biosimilar SB4 was approved April 29 by the Food and Drug Administration under the brand name Eticovo [etanercept-ykro]. It is also approved in other countries under the names Benepali and Brenzys.)

Accounting for erythrocyte sedimentation rate as a variable, Dr. Giunta and colleagues calculated disease activity scores based on 28 joints; 14 patients (35%) had plaque psoriasis (mean Psoriasis Area Severity Index [PASI] of 9.61 at baseline), while 26 (65%) had psoriatic arthritis (mean PASI, 4.69). All patients reported prior treatment with systemic conventional and biologic treatments. A group of 10 patients (25%) who had been previously treated with etanercept originator underwent an intermittent treatment regimen of 24 weeks with etanercept biosimilar, which was interrupted once clinical resolution was achieved. No treatments were prescribed between etanercept originator and etanercept biosimilar. Mean exposure was 50.4 weeks, ranging from 24 to 96 weeks, with an average washout period of 12.1 weeks from originator to biosimilar (range 8-24).

A significant improvement in mean PASI score was observed in plaque type psoriasis patients as well as psoriatic arthritis patients at week 24 (P less than .0001 and P less than .001, respectively), noted Dr. Giunta and associates.

“All scores achieved a statistical significant improvement with the exception of [swollen joint count] that markedly improved but not significantly,” they added. One patient experienced injection site reaction, but no serious adverse events were observed.

Despite low sample size and limited follow-up time, the authors concluded that etanercept biosimilar achieved effectiveness as a treatment for psoriatic patients even in cases involving previous exposure to originator etanercept. Cost savings of 61.58% for 50-mg treatment and 62.55% for 25-mg treatment respectively guaranteed “the continuity of etanercept-treated patients’ care and gave us the opportunity to allocate patients in innovative but more expensive agents with marginal increase in our annual budget,” they noted.

The authors reported serving as consultants and speakers for AbbVie, Biogen, Eli Lilly, Janssen, Pfizer, and Novartis.

SOURCE: Giunta A et al. Br J Dermatol. 2019 May 3. doi: 10.1111/bjd.18090.

The development of biosimilars such as etanercept SB4 offers a “significant opportunity to decrease medical care cost and increase treatment options,” Alessandro Giunta, MD, of the department of dermatology at the University of Rome Tor Vergata, and associates reported in a letter to the editor in the British Journal of Dermatology.

Dr. Giunta and his associates performed an observational, retrospective, single-center study to investigate etanercept biosimilar SB4 in patients being treated for plaque type psoriasis and psoriatic arthritis (PsA). They evaluated 40 patients – 21 men and 19 women – mean age 55, ranging from 19 to 79 years. The patients received the etanercept biosimilar SB4 between Oct. 21, 2016, and March 31, 2017, at University of Rome Tor Vergata’s department of dermatology. (The etanercept biosimilar SB4 was approved April 29 by the Food and Drug Administration under the brand name Eticovo [etanercept-ykro]. It is also approved in other countries under the names Benepali and Brenzys.)

Accounting for erythrocyte sedimentation rate as a variable, Dr. Giunta and colleagues calculated disease activity scores based on 28 joints; 14 patients (35%) had plaque psoriasis (mean Psoriasis Area Severity Index [PASI] of 9.61 at baseline), while 26 (65%) had psoriatic arthritis (mean PASI, 4.69). All patients reported prior treatment with systemic conventional and biologic treatments. A group of 10 patients (25%) who had been previously treated with etanercept originator underwent an intermittent treatment regimen of 24 weeks with etanercept biosimilar, which was interrupted once clinical resolution was achieved. No treatments were prescribed between etanercept originator and etanercept biosimilar. Mean exposure was 50.4 weeks, ranging from 24 to 96 weeks, with an average washout period of 12.1 weeks from originator to biosimilar (range 8-24).

A significant improvement in mean PASI score was observed in plaque type psoriasis patients as well as psoriatic arthritis patients at week 24 (P less than .0001 and P less than .001, respectively), noted Dr. Giunta and associates.

“All scores achieved a statistical significant improvement with the exception of [swollen joint count] that markedly improved but not significantly,” they added. One patient experienced injection site reaction, but no serious adverse events were observed.

Despite low sample size and limited follow-up time, the authors concluded that etanercept biosimilar achieved effectiveness as a treatment for psoriatic patients even in cases involving previous exposure to originator etanercept. Cost savings of 61.58% for 50-mg treatment and 62.55% for 25-mg treatment respectively guaranteed “the continuity of etanercept-treated patients’ care and gave us the opportunity to allocate patients in innovative but more expensive agents with marginal increase in our annual budget,” they noted.

The authors reported serving as consultants and speakers for AbbVie, Biogen, Eli Lilly, Janssen, Pfizer, and Novartis.

SOURCE: Giunta A et al. Br J Dermatol. 2019 May 3. doi: 10.1111/bjd.18090.

PHILADELPHIA – Fingolimod at a 0.5-mg dose had superior efficacy compared with glatiramer acetate in reducing disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to results from a phase 3b study reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.

Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.

“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.

While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.

The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.

Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.

The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.

Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.

The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.

Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.

Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.

He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.

Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.

Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

SOURCE: Cree B et al. AAN 2019, Abstract 56.009.

PHILADELPHIA – Fingolimod at a 0.5-mg dose had superior efficacy compared with glatiramer acetate in reducing disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to results from a phase 3b study reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.

Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.

“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.

While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.

The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.

Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.

The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.

Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.

The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.

Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.

Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.

He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.

Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.

Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

SOURCE: Cree B et al. AAN 2019, Abstract 56.009.

PHILADELPHIA – Fingolimod at a 0.5-mg dose had superior efficacy compared with glatiramer acetate in reducing disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to results from a phase 3b study reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.

Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.

“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.

While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.

The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.

Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.

The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.

Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.

The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.

Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.

Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.

He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.

Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.

Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

SOURCE: Cree B et al. AAN 2019, Abstract 56.009.

MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.

The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.

“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”

Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).

Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).

Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.

In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.

Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).

“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”

However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”

Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.

koakes@mdedge.com

MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.

The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.

“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”

Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).

Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).

Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.

In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.

Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).

“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”

However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”

Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.

koakes@mdedge.com

MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.

The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.

“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”

Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).

Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).

Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.

In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.

Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).

“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”

However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”

Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.

koakes@mdedge.com

Final guidance on the pathway for developers seeking licensure for “interchangeable” biologics was issued on May 10 by the Food and Drug Administration.

Courtesy University of North Carolina

The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.

Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.

On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”

“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.

The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.

Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.

The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.

“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.

Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”

The American College of Rheumatology applauded the FDA action.

“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.

“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
 

mdales@mdedge.com

Final guidance on the pathway for developers seeking licensure for “interchangeable” biologics was issued on May 10 by the Food and Drug Administration.

Courtesy University of North Carolina

The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.

Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.

On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”

“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.

The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.

Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.

The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.

“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.

Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”

The American College of Rheumatology applauded the FDA action.

“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.

“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
 

mdales@mdedge.com

Final guidance on the pathway for developers seeking licensure for “interchangeable” biologics was issued on May 10 by the Food and Drug Administration.

Courtesy University of North Carolina

The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.

Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.

On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”

“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.

The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.

Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.

The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.

“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.

Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”

The American College of Rheumatology applauded the FDA action.

“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.

“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
 

mdales@mdedge.com

CHICAGO – In patients with hidradenitis suppurativa (HS), infliximab started at 7.5 mg/kg was highly effective and well tolerated and may be a more appropriate starting dose than the 5 mg/kg that is recommended in the treatment of plaque psoriasis, according to a chart review presented as a late breaker at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

“Based on these data, we believe that a high starting dose of infliximab should be the new paradigm for this disease,” reported Justine Potemkin, a medical student at Albert Einstein College of Medicine, New York. The analysis was performed under the mentorship of Steven R. Cohen, MD, professor of dermatology and chief of the division of dermatology at Albert Einstein.

Infliximab, a tumor necrosis factor (TNF) blocker, is not approved for the treatment of HS, but it has been widely used following numerous reports of benefit in the literature, including a phase 2 randomized study published several years ago (J Am Acad Dermatol. 2010 Feb;62[2]:205-17), according to Ms. Potemkin.

“Based on dosing recommended for psoriasis, many hidradenitis suppurativa patients are started on 5 mg/kg, but doses of up to 10 mg/kg are within labeling for psoriasis, and our data support more aggressive initial treatment in patients with HS,” said Mondana Ghias, a research assistant in the department of dermatology at Albert Einstein, who was also involved in this study and joined Ms. Potemkin in presenting the data at the meeting.

In the chart review, 58 patients with moderate to severe HS initiated on 7.5 mg/kg of intravenous infliximab were identified. Due to a suboptimal response, 16 of these patients received 10 mg/kg infliximab in subsequent infusions, but the average response scores at 4 weeks compared favorably to previous reports with lower doses of infliximab, without increased toxicity.

“Starting with the 7.5 mg/kg dose with dose escalation if needed appears to provide a maximal response with minimal safety issues, based on our experience,” Ms. Potemkin reported.

At 4 weeks, a 10-point pain scale fell from a baseline mean of 5.65 to 1.34 (P less than .01). It reached 0.52 at week 12. The HS Physician Global Assessment (HS-PGA) fell from a baseline mean of 4.2 to 2.1 at week 4 (P less than .01) and then to 1.9 at week 12. The control of disease activity correlated with significant reductions in C-reactive protein and erythrocyte sedimentation rate.

The mean age in this patient population was 34.6 years. Slightly more than half (53.3%) were female. The average body mass index was 34.

“Obese patients also achieved a good response, which is consistent with weight-based dosing,” Ms. Potemkin reported.

The TNF blocker adalimumab is the only biologic and the only systemic therapy given regulatory approval for the treatment of HS, but Ms. Potemkin indicated that infliximab remains a widely used treatment option. She suggested that the responses observed in this patient series suggest infliximab is effective when used aggressively.

“No previous reports have examined the efficacy of high-dose infliximab,” Ms. Potemkin noted. “We think these findings are relevant to HS management.”

CHICAGO – In patients with hidradenitis suppurativa (HS), infliximab started at 7.5 mg/kg was highly effective and well tolerated and may be a more appropriate starting dose than the 5 mg/kg that is recommended in the treatment of plaque psoriasis, according to a chart review presented as a late breaker at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

“Based on these data, we believe that a high starting dose of infliximab should be the new paradigm for this disease,” reported Justine Potemkin, a medical student at Albert Einstein College of Medicine, New York. The analysis was performed under the mentorship of Steven R. Cohen, MD, professor of dermatology and chief of the division of dermatology at Albert Einstein.

Infliximab, a tumor necrosis factor (TNF) blocker, is not approved for the treatment of HS, but it has been widely used following numerous reports of benefit in the literature, including a phase 2 randomized study published several years ago (J Am Acad Dermatol. 2010 Feb;62[2]:205-17), according to Ms. Potemkin.

“Based on dosing recommended for psoriasis, many hidradenitis suppurativa patients are started on 5 mg/kg, but doses of up to 10 mg/kg are within labeling for psoriasis, and our data support more aggressive initial treatment in patients with HS,” said Mondana Ghias, a research assistant in the department of dermatology at Albert Einstein, who was also involved in this study and joined Ms. Potemkin in presenting the data at the meeting.

In the chart review, 58 patients with moderate to severe HS initiated on 7.5 mg/kg of intravenous infliximab were identified. Due to a suboptimal response, 16 of these patients received 10 mg/kg infliximab in subsequent infusions, but the average response scores at 4 weeks compared favorably to previous reports with lower doses of infliximab, without increased toxicity.

“Starting with the 7.5 mg/kg dose with dose escalation if needed appears to provide a maximal response with minimal safety issues, based on our experience,” Ms. Potemkin reported.

At 4 weeks, a 10-point pain scale fell from a baseline mean of 5.65 to 1.34 (P less than .01). It reached 0.52 at week 12. The HS Physician Global Assessment (HS-PGA) fell from a baseline mean of 4.2 to 2.1 at week 4 (P less than .01) and then to 1.9 at week 12. The control of disease activity correlated with significant reductions in C-reactive protein and erythrocyte sedimentation rate.

The mean age in this patient population was 34.6 years. Slightly more than half (53.3%) were female. The average body mass index was 34.

“Obese patients also achieved a good response, which is consistent with weight-based dosing,” Ms. Potemkin reported.

The TNF blocker adalimumab is the only biologic and the only systemic therapy given regulatory approval for the treatment of HS, but Ms. Potemkin indicated that infliximab remains a widely used treatment option. She suggested that the responses observed in this patient series suggest infliximab is effective when used aggressively.

“No previous reports have examined the efficacy of high-dose infliximab,” Ms. Potemkin noted. “We think these findings are relevant to HS management.”

CHICAGO – In patients with hidradenitis suppurativa (HS), infliximab started at 7.5 mg/kg was highly effective and well tolerated and may be a more appropriate starting dose than the 5 mg/kg that is recommended in the treatment of plaque psoriasis, according to a chart review presented as a late breaker at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

“Based on these data, we believe that a high starting dose of infliximab should be the new paradigm for this disease,” reported Justine Potemkin, a medical student at Albert Einstein College of Medicine, New York. The analysis was performed under the mentorship of Steven R. Cohen, MD, professor of dermatology and chief of the division of dermatology at Albert Einstein.

Infliximab, a tumor necrosis factor (TNF) blocker, is not approved for the treatment of HS, but it has been widely used following numerous reports of benefit in the literature, including a phase 2 randomized study published several years ago (J Am Acad Dermatol. 2010 Feb;62[2]:205-17), according to Ms. Potemkin.

“Based on dosing recommended for psoriasis, many hidradenitis suppurativa patients are started on 5 mg/kg, but doses of up to 10 mg/kg are within labeling for psoriasis, and our data support more aggressive initial treatment in patients with HS,” said Mondana Ghias, a research assistant in the department of dermatology at Albert Einstein, who was also involved in this study and joined Ms. Potemkin in presenting the data at the meeting.

In the chart review, 58 patients with moderate to severe HS initiated on 7.5 mg/kg of intravenous infliximab were identified. Due to a suboptimal response, 16 of these patients received 10 mg/kg infliximab in subsequent infusions, but the average response scores at 4 weeks compared favorably to previous reports with lower doses of infliximab, without increased toxicity.

“Starting with the 7.5 mg/kg dose with dose escalation if needed appears to provide a maximal response with minimal safety issues, based on our experience,” Ms. Potemkin reported.

At 4 weeks, a 10-point pain scale fell from a baseline mean of 5.65 to 1.34 (P less than .01). It reached 0.52 at week 12. The HS Physician Global Assessment (HS-PGA) fell from a baseline mean of 4.2 to 2.1 at week 4 (P less than .01) and then to 1.9 at week 12. The control of disease activity correlated with significant reductions in C-reactive protein and erythrocyte sedimentation rate.

The mean age in this patient population was 34.6 years. Slightly more than half (53.3%) were female. The average body mass index was 34.

“Obese patients also achieved a good response, which is consistent with weight-based dosing,” Ms. Potemkin reported.

The TNF blocker adalimumab is the only biologic and the only systemic therapy given regulatory approval for the treatment of HS, but Ms. Potemkin indicated that infliximab remains a widely used treatment option. She suggested that the responses observed in this patient series suggest infliximab is effective when used aggressively.

“No previous reports have examined the efficacy of high-dose infliximab,” Ms. Potemkin noted. “We think these findings are relevant to HS management.”

CHICAGO – Because of the very substantial risk of metastatic spread, baseline imaging should be performed in all patients with Merkel cell carcinoma (MCC), including those without palpable lymph nodes, according to results of an analysis of a large MCC registry presented at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

The results were a “surprise,” according to Neha Singh, a researcher in the division of dermatology at the University of Washington, Seattle. She contended that many treatment guidelines for MCC, including imaging at the time of diagnosis, are borrowed from those developed for melanoma but should not be.

“MCC is much more frequently metastatic to regional and distant sites than melanoma, so current melanoma guidelines may not be appropriate for use with MCC,” she said. According to the data she cited, 41% of MCC patients, versus 14% of melanoma patients, already have metastatic disease at the time of diagnosis.

The presence of more aggressive disease and the need for scanning was confirmed in the analysis of the MCC Registry in Seattle, which contains 1,439 patients. Of 586 patients who met inclusion criteria for this analysis, 493 MCC patients had no palpable lymph nodes at the time of diagnosis. Yet, 60 (12%) proved to already have regional or distant metastases on the basis of scans.

This contrasts starkly with melanoma data, according to Ms. Singh. Guidelines from the National Comprehensive Cancer Network (NCCN) do not recommend scans in melanoma patients without palpable lymph nodes based on evidence that only 1% of these will be upstaged by imaging. This figure was judged too small to justify routine scans, she said.

In melanoma patients with palpable lymph nodes, NCCN guidelines do recommend imaging at diagnosis because upstaging is common, and the same is true in MCC, Ms. Singh noted. In the Seattle registry, 10 (11%) of the 93 patients with palpable lymph nodes were upstaged for distant metastases found on imaging.

In those without palpable lymph nodes, “even a small tumor does not guarantee the absence of distant metastases,” Ms. Singh cautioned. Although the median tumor size in this group was 2.3 cm, tumors of less than 1 cm were still associated with distant disease.

The likelihood of distant disease in MCC patients without palpable lymph nodes might be even greater than that identified in this analysis. At least some of the patients in this series were evaluated with CT rather than PET imaging, which is more sensitive. Ms. Singh reported that no stratification to determine rates of distant disease by imaging type have yet been undertaken in this dataset.

Based on these findings, guidelines for MCC should include consideration of baseline imaging in all patients, Ms. Singh said. In making this point, she also emphasized the guidelines for melanoma should not be considered transferable to MCC.

“Why is this important?” Ms. Singh asked. Understaging MCC “may lead to inadequate surgery, overaggressive local therapy, and a potential delay to effective systemic therapy.”

CHICAGO – Because of the very substantial risk of metastatic spread, baseline imaging should be performed in all patients with Merkel cell carcinoma (MCC), including those without palpable lymph nodes, according to results of an analysis of a large MCC registry presented at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

The results were a “surprise,” according to Neha Singh, a researcher in the division of dermatology at the University of Washington, Seattle. She contended that many treatment guidelines for MCC, including imaging at the time of diagnosis, are borrowed from those developed for melanoma but should not be.

“MCC is much more frequently metastatic to regional and distant sites than melanoma, so current melanoma guidelines may not be appropriate for use with MCC,” she said. According to the data she cited, 41% of MCC patients, versus 14% of melanoma patients, already have metastatic disease at the time of diagnosis.

The presence of more aggressive disease and the need for scanning was confirmed in the analysis of the MCC Registry in Seattle, which contains 1,439 patients. Of 586 patients who met inclusion criteria for this analysis, 493 MCC patients had no palpable lymph nodes at the time of diagnosis. Yet, 60 (12%) proved to already have regional or distant metastases on the basis of scans.

This contrasts starkly with melanoma data, according to Ms. Singh. Guidelines from the National Comprehensive Cancer Network (NCCN) do not recommend scans in melanoma patients without palpable lymph nodes based on evidence that only 1% of these will be upstaged by imaging. This figure was judged too small to justify routine scans, she said.

In melanoma patients with palpable lymph nodes, NCCN guidelines do recommend imaging at diagnosis because upstaging is common, and the same is true in MCC, Ms. Singh noted. In the Seattle registry, 10 (11%) of the 93 patients with palpable lymph nodes were upstaged for distant metastases found on imaging.

In those without palpable lymph nodes, “even a small tumor does not guarantee the absence of distant metastases,” Ms. Singh cautioned. Although the median tumor size in this group was 2.3 cm, tumors of less than 1 cm were still associated with distant disease.

The likelihood of distant disease in MCC patients without palpable lymph nodes might be even greater than that identified in this analysis. At least some of the patients in this series were evaluated with CT rather than PET imaging, which is more sensitive. Ms. Singh reported that no stratification to determine rates of distant disease by imaging type have yet been undertaken in this dataset.

Based on these findings, guidelines for MCC should include consideration of baseline imaging in all patients, Ms. Singh said. In making this point, she also emphasized the guidelines for melanoma should not be considered transferable to MCC.

“Why is this important?” Ms. Singh asked. Understaging MCC “may lead to inadequate surgery, overaggressive local therapy, and a potential delay to effective systemic therapy.”

CHICAGO – Because of the very substantial risk of metastatic spread, baseline imaging should be performed in all patients with Merkel cell carcinoma (MCC), including those without palpable lymph nodes, according to results of an analysis of a large MCC registry presented at the annual meeting of the Society for Investigative Dermatology.

Ted Bosworth/MDedge News

The results were a “surprise,” according to Neha Singh, a researcher in the division of dermatology at the University of Washington, Seattle. She contended that many treatment guidelines for MCC, including imaging at the time of diagnosis, are borrowed from those developed for melanoma but should not be.

“MCC is much more frequently metastatic to regional and distant sites than melanoma, so current melanoma guidelines may not be appropriate for use with MCC,” she said. According to the data she cited, 41% of MCC patients, versus 14% of melanoma patients, already have metastatic disease at the time of diagnosis.

The presence of more aggressive disease and the need for scanning was confirmed in the analysis of the MCC Registry in Seattle, which contains 1,439 patients. Of 586 patients who met inclusion criteria for this analysis, 493 MCC patients had no palpable lymph nodes at the time of diagnosis. Yet, 60 (12%) proved to already have regional or distant metastases on the basis of scans.

This contrasts starkly with melanoma data, according to Ms. Singh. Guidelines from the National Comprehensive Cancer Network (NCCN) do not recommend scans in melanoma patients without palpable lymph nodes based on evidence that only 1% of these will be upstaged by imaging. This figure was judged too small to justify routine scans, she said.

In melanoma patients with palpable lymph nodes, NCCN guidelines do recommend imaging at diagnosis because upstaging is common, and the same is true in MCC, Ms. Singh noted. In the Seattle registry, 10 (11%) of the 93 patients with palpable lymph nodes were upstaged for distant metastases found on imaging.

In those without palpable lymph nodes, “even a small tumor does not guarantee the absence of distant metastases,” Ms. Singh cautioned. Although the median tumor size in this group was 2.3 cm, tumors of less than 1 cm were still associated with distant disease.

The likelihood of distant disease in MCC patients without palpable lymph nodes might be even greater than that identified in this analysis. At least some of the patients in this series were evaluated with CT rather than PET imaging, which is more sensitive. Ms. Singh reported that no stratification to determine rates of distant disease by imaging type have yet been undertaken in this dataset.

Based on these findings, guidelines for MCC should include consideration of baseline imaging in all patients, Ms. Singh said. In making this point, she also emphasized the guidelines for melanoma should not be considered transferable to MCC.

“Why is this important?” Ms. Singh asked. Understaging MCC “may lead to inadequate surgery, overaggressive local therapy, and a potential delay to effective systemic therapy.”

Scleromyxedema
 

Scleromyxedema is an uncommon disease affecting middle-aged adults and typically presents with numerous waxy, monomorphic papules on the head and neck area, characteristically involving the glabella and ears. In some patients, the skin may be intensely pruritic, but this is not a universal finding and varies considerably among patients. In addition to affecting the skin, scleromyxedema has variable multisystem effects on the gastrointestinal tract, and musculoskeletal, pulmonary, cardiovascular, renal, and central nervous systems. The most common symptoms are proximal muscle weakness, dysphagia, and dyspnea on exertion. Scleromyxedema can also be associated with a paraproteinemia, mainly immunoglobulin G-lambda type.

Courtesy Jennifer Maldonado

Scleromyxedema shares some features with other cutaneous diseases, and the main differential diagnosis includes localized scleromyxedema, also known as lichen myxedematosus. Lichen myxedematosus presents with waxy, firm papules and plaques. Systemic involvement and monoclonal gammopathy are characteristically absent. Scleroderma differs given the increase in fibrosis of cutaneous lesions, a higher percentage of Raynaud’s phenomenon, prominent lung disease, and autoantibodies.

On histopathologic review, scleromyxedema is associated with papular and mucin deposition, and increased fibroblast proliferation. The punch biopsy of the exhibited patient demonstrated a dome-shaped dermal nodule composed of fibroblasts in an edematous stroma. An Alcian blue stain highlighted increased mucin in the dermis and S-100 staining highlighted rare cells in the dermis.

The treatment of choice for scleromyxedema varies but includes intravenous immunoglobulins, systemic glucocorticosteroids, thalidomide, or immunosuppressant medications. In this patient, an IgG paraproteinemia was found on serum protein electrophoresis. The patient was evaluated by hematology-oncology, and no underlying myeloproliferative or dysplastic disease was found. The patient was started on intravenous immunoglobulin infusions with near complete resolution of his eruption and arthritic symptoms.

This case and photo were submitted by Jennifer Maldonado, a medical student at Nova Southeastern University, Ft. Lauderdale, Fla., and Kate Oberlin, MD, and Brian Morrison, MD, of the department of dermatology and cutaneous surgery, University of Miami; and Michelle Demory Beckler, PhD, of the College of Osteopathic Medicine and the department of microbiology, College of Medical Sciences, Nova Southeastern University.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

Scleromyxedema
 

Scleromyxedema is an uncommon disease affecting middle-aged adults and typically presents with numerous waxy, monomorphic papules on the head and neck area, characteristically involving the glabella and ears. In some patients, the skin may be intensely pruritic, but this is not a universal finding and varies considerably among patients. In addition to affecting the skin, scleromyxedema has variable multisystem effects on the gastrointestinal tract, and musculoskeletal, pulmonary, cardiovascular, renal, and central nervous systems. The most common symptoms are proximal muscle weakness, dysphagia, and dyspnea on exertion. Scleromyxedema can also be associated with a paraproteinemia, mainly immunoglobulin G-lambda type.

Courtesy Jennifer Maldonado

Scleromyxedema shares some features with other cutaneous diseases, and the main differential diagnosis includes localized scleromyxedema, also known as lichen myxedematosus. Lichen myxedematosus presents with waxy, firm papules and plaques. Systemic involvement and monoclonal gammopathy are characteristically absent. Scleroderma differs given the increase in fibrosis of cutaneous lesions, a higher percentage of Raynaud’s phenomenon, prominent lung disease, and autoantibodies.

On histopathologic review, scleromyxedema is associated with papular and mucin deposition, and increased fibroblast proliferation. The punch biopsy of the exhibited patient demonstrated a dome-shaped dermal nodule composed of fibroblasts in an edematous stroma. An Alcian blue stain highlighted increased mucin in the dermis and S-100 staining highlighted rare cells in the dermis.

The treatment of choice for scleromyxedema varies but includes intravenous immunoglobulins, systemic glucocorticosteroids, thalidomide, or immunosuppressant medications. In this patient, an IgG paraproteinemia was found on serum protein electrophoresis. The patient was evaluated by hematology-oncology, and no underlying myeloproliferative or dysplastic disease was found. The patient was started on intravenous immunoglobulin infusions with near complete resolution of his eruption and arthritic symptoms.

This case and photo were submitted by Jennifer Maldonado, a medical student at Nova Southeastern University, Ft. Lauderdale, Fla., and Kate Oberlin, MD, and Brian Morrison, MD, of the department of dermatology and cutaneous surgery, University of Miami; and Michelle Demory Beckler, PhD, of the College of Osteopathic Medicine and the department of microbiology, College of Medical Sciences, Nova Southeastern University.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

Scleromyxedema
 

Scleromyxedema is an uncommon disease affecting middle-aged adults and typically presents with numerous waxy, monomorphic papules on the head and neck area, characteristically involving the glabella and ears. In some patients, the skin may be intensely pruritic, but this is not a universal finding and varies considerably among patients. In addition to affecting the skin, scleromyxedema has variable multisystem effects on the gastrointestinal tract, and musculoskeletal, pulmonary, cardiovascular, renal, and central nervous systems. The most common symptoms are proximal muscle weakness, dysphagia, and dyspnea on exertion. Scleromyxedema can also be associated with a paraproteinemia, mainly immunoglobulin G-lambda type.

Courtesy Jennifer Maldonado

Scleromyxedema shares some features with other cutaneous diseases, and the main differential diagnosis includes localized scleromyxedema, also known as lichen myxedematosus. Lichen myxedematosus presents with waxy, firm papules and plaques. Systemic involvement and monoclonal gammopathy are characteristically absent. Scleroderma differs given the increase in fibrosis of cutaneous lesions, a higher percentage of Raynaud’s phenomenon, prominent lung disease, and autoantibodies.

On histopathologic review, scleromyxedema is associated with papular and mucin deposition, and increased fibroblast proliferation. The punch biopsy of the exhibited patient demonstrated a dome-shaped dermal nodule composed of fibroblasts in an edematous stroma. An Alcian blue stain highlighted increased mucin in the dermis and S-100 staining highlighted rare cells in the dermis.

The treatment of choice for scleromyxedema varies but includes intravenous immunoglobulins, systemic glucocorticosteroids, thalidomide, or immunosuppressant medications. In this patient, an IgG paraproteinemia was found on serum protein electrophoresis. The patient was evaluated by hematology-oncology, and no underlying myeloproliferative or dysplastic disease was found. The patient was started on intravenous immunoglobulin infusions with near complete resolution of his eruption and arthritic symptoms.

This case and photo were submitted by Jennifer Maldonado, a medical student at Nova Southeastern University, Ft. Lauderdale, Fla., and Kate Oberlin, MD, and Brian Morrison, MD, of the department of dermatology and cutaneous surgery, University of Miami; and Michelle Demory Beckler, PhD, of the College of Osteopathic Medicine and the department of microbiology, College of Medical Sciences, Nova Southeastern University.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

Twin versus singleton pregnancies confer a 300% increased risk of severe acute maternal complications, and 21% of that risk is mediated by cesarean delivery, according to findings from the prospective EPIMOMS study.

micheldenijs/iStock/Getty Images Plus

The population-based incidence of severe acute maternal morbidity occurring between 22 weeks’ of gestation and 42 days post partum in the 2012-2013 French multicenter study was 6.2% among 3,202 twin pregnancies and 1.3% among 179,107 singleton pregnancies, Hugo Madar, MD, MPH, of Bordeaux University Hospital, France, and colleagues reported on behalf of the EPIMOMS (Epidémiologie de la Morbidité Maternelle Sévère) study group.

For the current analysis – a population-based, cohort-nested, case-control analysis of study data – the investigators compared 2,500 case patients (8% had twin pregnancies) and 3,650 controls (2% had twin pregnancies) who did not experience severe acute maternal morbidity during that time period (odds ratio, 4.7). After accounting for confounding factors, the increased risk among women with twin versus singleton pregnancies persisted (OR, 4.2) during both the antepartum (OR, 4.1) and intrapartum/postpartum (OR, 4.2) periods.

The majority of events (77%) occurred during the latter periods, and the two most common underlying causal conditions were severe obstetric hemorrhage (66%) and severe hypertensive complications (20%); however, the increased risk in twin pregnancies was apparent, regardless of the underlying cause.

The cesarean delivery rates for twin versus singleton pregnancies were 72% and 34%, respectively, in the case group, and 58% and 18%, respectively, in the control group. A path analysis taking potential indication bias into account showed that 21% of the total risk of intrapartum or postpartum severe acute maternal morbidity risk associated with twin pregnancy was mediated by cesarean delivery, Dr. Madar and associates noted, explaining that, “in other words, if twin pregnancies had the same probability of cesarean delivery as singleton pregnancies, the association found between twin pregnancy and intrapartum or postpartum severe acute maternal morbidity would be reduced by one-fifth.”

This provides further support for limiting the use of cesarean for twin deliveries to cases with clear medical indications, as increasing the rate of vaginal deliveries may decrease the rate of severe acute maternal morbidity, they concluded.

EPIMOMS was supported by the National Research Agency and the Ile de France Regional Health Agency. Dr. Madar received a training grant from the Aquitaine Regional Health Agency. The authors reported having no other relevant financial disclosures.

sworcester@mdedge.com

SOURCE: Madar H et al. Obstet Gynecol. 2019;133:1141-50.

Twin versus singleton pregnancies confer a 300% increased risk of severe acute maternal complications, and 21% of that risk is mediated by cesarean delivery, according to findings from the prospective EPIMOMS study.

micheldenijs/iStock/Getty Images Plus

The population-based incidence of severe acute maternal morbidity occurring between 22 weeks’ of gestation and 42 days post partum in the 2012-2013 French multicenter study was 6.2% among 3,202 twin pregnancies and 1.3% among 179,107 singleton pregnancies, Hugo Madar, MD, MPH, of Bordeaux University Hospital, France, and colleagues reported on behalf of the EPIMOMS (Epidémiologie de la Morbidité Maternelle Sévère) study group.

For the current analysis – a population-based, cohort-nested, case-control analysis of study data – the investigators compared 2,500 case patients (8% had twin pregnancies) and 3,650 controls (2% had twin pregnancies) who did not experience severe acute maternal morbidity during that time period (odds ratio, 4.7). After accounting for confounding factors, the increased risk among women with twin versus singleton pregnancies persisted (OR, 4.2) during both the antepartum (OR, 4.1) and intrapartum/postpartum (OR, 4.2) periods.

The majority of events (77%) occurred during the latter periods, and the two most common underlying causal conditions were severe obstetric hemorrhage (66%) and severe hypertensive complications (20%); however, the increased risk in twin pregnancies was apparent, regardless of the underlying cause.

The cesarean delivery rates for twin versus singleton pregnancies were 72% and 34%, respectively, in the case group, and 58% and 18%, respectively, in the control group. A path analysis taking potential indication bias into account showed that 21% of the total risk of intrapartum or postpartum severe acute maternal morbidity risk associated with twin pregnancy was mediated by cesarean delivery, Dr. Madar and associates noted, explaining that, “in other words, if twin pregnancies had the same probability of cesarean delivery as singleton pregnancies, the association found between twin pregnancy and intrapartum or postpartum severe acute maternal morbidity would be reduced by one-fifth.”

This provides further support for limiting the use of cesarean for twin deliveries to cases with clear medical indications, as increasing the rate of vaginal deliveries may decrease the rate of severe acute maternal morbidity, they concluded.

EPIMOMS was supported by the National Research Agency and the Ile de France Regional Health Agency. Dr. Madar received a training grant from the Aquitaine Regional Health Agency. The authors reported having no other relevant financial disclosures.

sworcester@mdedge.com

SOURCE: Madar H et al. Obstet Gynecol. 2019;133:1141-50.

Twin versus singleton pregnancies confer a 300% increased risk of severe acute maternal complications, and 21% of that risk is mediated by cesarean delivery, according to findings from the prospective EPIMOMS study.

micheldenijs/iStock/Getty Images Plus

The population-based incidence of severe acute maternal morbidity occurring between 22 weeks’ of gestation and 42 days post partum in the 2012-2013 French multicenter study was 6.2% among 3,202 twin pregnancies and 1.3% among 179,107 singleton pregnancies, Hugo Madar, MD, MPH, of Bordeaux University Hospital, France, and colleagues reported on behalf of the EPIMOMS (Epidémiologie de la Morbidité Maternelle Sévère) study group.

For the current analysis – a population-based, cohort-nested, case-control analysis of study data – the investigators compared 2,500 case patients (8% had twin pregnancies) and 3,650 controls (2% had twin pregnancies) who did not experience severe acute maternal morbidity during that time period (odds ratio, 4.7). After accounting for confounding factors, the increased risk among women with twin versus singleton pregnancies persisted (OR, 4.2) during both the antepartum (OR, 4.1) and intrapartum/postpartum (OR, 4.2) periods.

The majority of events (77%) occurred during the latter periods, and the two most common underlying causal conditions were severe obstetric hemorrhage (66%) and severe hypertensive complications (20%); however, the increased risk in twin pregnancies was apparent, regardless of the underlying cause.

The cesarean delivery rates for twin versus singleton pregnancies were 72% and 34%, respectively, in the case group, and 58% and 18%, respectively, in the control group. A path analysis taking potential indication bias into account showed that 21% of the total risk of intrapartum or postpartum severe acute maternal morbidity risk associated with twin pregnancy was mediated by cesarean delivery, Dr. Madar and associates noted, explaining that, “in other words, if twin pregnancies had the same probability of cesarean delivery as singleton pregnancies, the association found between twin pregnancy and intrapartum or postpartum severe acute maternal morbidity would be reduced by one-fifth.”

This provides further support for limiting the use of cesarean for twin deliveries to cases with clear medical indications, as increasing the rate of vaginal deliveries may decrease the rate of severe acute maternal morbidity, they concluded.

EPIMOMS was supported by the National Research Agency and the Ile de France Regional Health Agency. Dr. Madar received a training grant from the Aquitaine Regional Health Agency. The authors reported having no other relevant financial disclosures.

sworcester@mdedge.com

SOURCE: Madar H et al. Obstet Gynecol. 2019;133:1141-50.

LOS ANGELES – Patients who took the sodium-glucose cotransporter-2 inhibitor canagliflozin after undergoing metabolic surgery experienced reductions in blood glucose, body mass index, and truncal body fat, results from a small pilot study have shown.

Doug Brunk/MDedge News

“We hypothesized that canagliflozin would be a good choice for these patients, because these drugs work independently of insulin,” the study’s principal investigator, Sangeeta R. Kashyap, MD, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “They help promote weight loss and improve blood pressure. [After] bariatric surgery, patients have an issue with weight regain, and sometimes their diabetes comes back.”

In what she said is the first prospective, randomized, controlled trial of its kind, Dr. Kashyap, an endocrinologist at the Cleveland Clinic, and her colleagues enrolled 11 women and 5 men with type 2 diabetes who had undergone Roux-en-Y gastric bypass or sleeve gastrectomy to study the effects of canagliflozin on clinical parameters over a period of 6 months. At baseline, the patients’ mean body mass index was 39.2 kg/m² and their mean hemoglobin A_1c level was 7.4%. The researchers used maximum likelihood estimation in a linear mixed-effect model to deduce differences between the treatment and placebo groups. Patients randomized to the study drug were assigned a 6-month course of canagliflozin, starting on 100 mg for 2 weeks titrated up to 300 mg daily.

At 6 months, fasting glucose was significantly reduced in the canagliflozin group, compared with baseline (from 163 to 122 mg/dL; P = .007), but it rose in the placebo group (from 164 to 192 mg/dL), a between-group difference that fell short of statistical significance (P = .12). In addition, C-reactive protein in the treatment group fell from 8.9 mg/L to 3.9 mg/L, but rose from 1.6 mg/L to 4.7 mg/L in the placebo group, a between-group difference that trended toward significance (P = .07).

During the 6-month study period, the mean BMI fell from 39.6 kg/m² to 38 kg/m² in the canagliflozin group but increased from 38 to 41 in the placebo group, a between-group difference that reached statistical significance (P = .014). Mean changes in body fat (a reduction of 1.82%), truncal fat (a reduction of 2.67%), and android fat (a reduction of 3%) also reached statistical significance in the treatment group, compared with the placebo group. Reductions in adiponectin, leptin, and high–molecular weight adiponectin did not reach statistical significance.

“I think these drugs have a place in post–bariatric surgery care,” Dr. Kashyap said. “Canagliflozin after metabolic surgery improved weight-loss outcomes and blood sugar levels. It also improved abdominal fat levels, and in this way might even lower cardiovascular disease risk in these patients.”

She acknowledged the study’s small sample size and single-center design as limitations. “It was very difficult to recruit patients for this study,” she said. “Not many patients have recurrent diabetes after bariatric surgery.”

Janssen provided funding to Dr. Kashyap for the trial.

dbrunk@mdedge.com

LOS ANGELES – Patients who took the sodium-glucose cotransporter-2 inhibitor canagliflozin after undergoing metabolic surgery experienced reductions in blood glucose, body mass index, and truncal body fat, results from a small pilot study have shown.

Doug Brunk/MDedge News

“We hypothesized that canagliflozin would be a good choice for these patients, because these drugs work independently of insulin,” the study’s principal investigator, Sangeeta R. Kashyap, MD, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “They help promote weight loss and improve blood pressure. [After] bariatric surgery, patients have an issue with weight regain, and sometimes their diabetes comes back.”

In what she said is the first prospective, randomized, controlled trial of its kind, Dr. Kashyap, an endocrinologist at the Cleveland Clinic, and her colleagues enrolled 11 women and 5 men with type 2 diabetes who had undergone Roux-en-Y gastric bypass or sleeve gastrectomy to study the effects of canagliflozin on clinical parameters over a period of 6 months. At baseline, the patients’ mean body mass index was 39.2 kg/m² and their mean hemoglobin A_1c level was 7.4%. The researchers used maximum likelihood estimation in a linear mixed-effect model to deduce differences between the treatment and placebo groups. Patients randomized to the study drug were assigned a 6-month course of canagliflozin, starting on 100 mg for 2 weeks titrated up to 300 mg daily.

At 6 months, fasting glucose was significantly reduced in the canagliflozin group, compared with baseline (from 163 to 122 mg/dL; P = .007), but it rose in the placebo group (from 164 to 192 mg/dL), a between-group difference that fell short of statistical significance (P = .12). In addition, C-reactive protein in the treatment group fell from 8.9 mg/L to 3.9 mg/L, but rose from 1.6 mg/L to 4.7 mg/L in the placebo group, a between-group difference that trended toward significance (P = .07).

During the 6-month study period, the mean BMI fell from 39.6 kg/m² to 38 kg/m² in the canagliflozin group but increased from 38 to 41 in the placebo group, a between-group difference that reached statistical significance (P = .014). Mean changes in body fat (a reduction of 1.82%), truncal fat (a reduction of 2.67%), and android fat (a reduction of 3%) also reached statistical significance in the treatment group, compared with the placebo group. Reductions in adiponectin, leptin, and high–molecular weight adiponectin did not reach statistical significance.

“I think these drugs have a place in post–bariatric surgery care,” Dr. Kashyap said. “Canagliflozin after metabolic surgery improved weight-loss outcomes and blood sugar levels. It also improved abdominal fat levels, and in this way might even lower cardiovascular disease risk in these patients.”

She acknowledged the study’s small sample size and single-center design as limitations. “It was very difficult to recruit patients for this study,” she said. “Not many patients have recurrent diabetes after bariatric surgery.”

Janssen provided funding to Dr. Kashyap for the trial.

dbrunk@mdedge.com

LOS ANGELES – Patients who took the sodium-glucose cotransporter-2 inhibitor canagliflozin after undergoing metabolic surgery experienced reductions in blood glucose, body mass index, and truncal body fat, results from a small pilot study have shown.

Doug Brunk/MDedge News

“We hypothesized that canagliflozin would be a good choice for these patients, because these drugs work independently of insulin,” the study’s principal investigator, Sangeeta R. Kashyap, MD, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “They help promote weight loss and improve blood pressure. [After] bariatric surgery, patients have an issue with weight regain, and sometimes their diabetes comes back.”

In what she said is the first prospective, randomized, controlled trial of its kind, Dr. Kashyap, an endocrinologist at the Cleveland Clinic, and her colleagues enrolled 11 women and 5 men with type 2 diabetes who had undergone Roux-en-Y gastric bypass or sleeve gastrectomy to study the effects of canagliflozin on clinical parameters over a period of 6 months. At baseline, the patients’ mean body mass index was 39.2 kg/m² and their mean hemoglobin A_1c level was 7.4%. The researchers used maximum likelihood estimation in a linear mixed-effect model to deduce differences between the treatment and placebo groups. Patients randomized to the study drug were assigned a 6-month course of canagliflozin, starting on 100 mg for 2 weeks titrated up to 300 mg daily.

At 6 months, fasting glucose was significantly reduced in the canagliflozin group, compared with baseline (from 163 to 122 mg/dL; P = .007), but it rose in the placebo group (from 164 to 192 mg/dL), a between-group difference that fell short of statistical significance (P = .12). In addition, C-reactive protein in the treatment group fell from 8.9 mg/L to 3.9 mg/L, but rose from 1.6 mg/L to 4.7 mg/L in the placebo group, a between-group difference that trended toward significance (P = .07).

During the 6-month study period, the mean BMI fell from 39.6 kg/m² to 38 kg/m² in the canagliflozin group but increased from 38 to 41 in the placebo group, a between-group difference that reached statistical significance (P = .014). Mean changes in body fat (a reduction of 1.82%), truncal fat (a reduction of 2.67%), and android fat (a reduction of 3%) also reached statistical significance in the treatment group, compared with the placebo group. Reductions in adiponectin, leptin, and high–molecular weight adiponectin did not reach statistical significance.

“I think these drugs have a place in post–bariatric surgery care,” Dr. Kashyap said. “Canagliflozin after metabolic surgery improved weight-loss outcomes and blood sugar levels. It also improved abdominal fat levels, and in this way might even lower cardiovascular disease risk in these patients.”

She acknowledged the study’s small sample size and single-center design as limitations. “It was very difficult to recruit patients for this study,” she said. “Not many patients have recurrent diabetes after bariatric surgery.”

Janssen provided funding to Dr. Kashyap for the trial.

dbrunk@mdedge.com

BALTIMORE – More than half of office visits where an adolescent receives an influenza vaccine represent missed opportunities to get a human papillomavirus (HPV) vaccine, according to a study.

Joseph Abbott/Thinkstock

“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”

According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.

Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.

The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.

The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.

The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.

In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.

Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).

“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.

It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.

Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.

“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.

The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.

The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.

BALTIMORE – More than half of office visits where an adolescent receives an influenza vaccine represent missed opportunities to get a human papillomavirus (HPV) vaccine, according to a study.

Joseph Abbott/Thinkstock

“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”

According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.

Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.

The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.

The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.

The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.

In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.

Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).

“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.

It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.

Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.

“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.

The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.

The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.

BALTIMORE – More than half of office visits where an adolescent receives an influenza vaccine represent missed opportunities to get a human papillomavirus (HPV) vaccine, according to a study.

Joseph Abbott/Thinkstock

“Overall in preventive visits, missed opportunities were much higher for HPV, compared to the other two vaccines” recommended for adolescents, MenACWY (meningococcal conjugate vaccine) and Tdap, Mary Kate Kelly, MPH, of Children’s Hospital of Philadelphia, told attendees at the Pediatric Academic Societies annual meeting. “In order to increase vaccination rates, it’s essential to implement efforts to reduce missed opportunities.”

According to 2018 Centers for Disease Control and Prevention data, Ms. Kelly said, vaccine coverage for the HPV vaccine is approximately 66%, compared with 85% for the MenACWY vaccine and 89% for the Tdap vaccine.

Ms. Kelly and her colleagues investigated how often children or adolescents missed an opportunity to get an HPV vaccine when they received an influenza vaccine during an office visit. This study was part of the larger STOP HPV trial funded by the National Institutes of Health and aimed at implementing evidence-based interventions to reduce missed opportunities for HPV vaccination in primary care.

The researchers retrospectively reviewed EHRs from 2015 to 2018 for 48 pediatric practices across 19 states. All practices were part of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS) national pediatric primary care network. The researchers isolated all visits for patients aged 11-17 years who received their flu vaccine and were eligible to receive the HPV vaccine.

The investigators defined a missed opportunity as one in which a patient was due for the HPV vaccine but did not receive one at the visit when they received their flu vaccine.

The study involved 40,129 patients who received the flu vaccine at 52,818 visits when they also were eligible to receive the HPV vaccine. The median age of patients was 12 years old, and 47% were female.

In 68% of visits, the patient could have received an HPV vaccine but did not – even though they were due and eligible for one. The rate was the same for boys and for girls. By contrast, only 38% of visits involved a missed opportunity for the MenACWY vaccines and 39% for the Tdap vaccine.

Rates of missed opportunities for HPV vaccination ranged among individual practices from 22% to 81% of overall visits. Patients were more than twice as likely to miss the opportunity for an HPV vaccine dose if it would have been their first dose – 70% of missed opportunities – versus being a second or third dose, which comprised 30% of missed opportunities (adjusted relative risk, 2.48; P less than .001)).

“However, missed opportunities were also common for subsequent HPV doses when vaccine hesitancy is less likely to be an issue,” Ms. Kelly added.

It also was much more likely that missed opportunities occurred during nurse visits or visits for an acute or chronic condition rather than preventive visits, which made up about half (51%) of all visits analyzed. While 48% of preventive visits involved a missed opportunity, 93% of nurse visits (aRR compared with preventive, 2.18; P less than.001) and 89% of acute or chronic visits (aRR, 2.11; P less than .001) did.

Percentages of missed opportunities were similarly high for the MenACWY and Tdap vaccines at nurse visits and acute/chronic visits, but much lower at preventive visits for the MenACWY (12%) and Tdap (15%) vaccines.

“Increasing simultaneous administration of HPV and other adolescent vaccines with the influenza vaccine may help to improve coverage,” Ms. Kelly concluded.

The study was limited by its use of a convenience sample from practices that were interested in participating and willing to stock the HPV vaccine. Additionally, the researchers could not detect or adjust for EHR errors or inaccurate or incomplete vaccine histories, and they were unable to look at vaccine hesitancy or refusal with the EHRs.

The research was funded by the National Institutes of Health, the U.S. Department of Health & Human Services, and the National Research Network to Improve Children’s Health. The authors reported no relevant financial disclosures.