MDedge Rheumatology

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

A COVID-19 vaccine could be proven effective within the last months of 2020, with distribution of first doses possible before the end of the year, according to Anthony S. Fauci, MD, director, National Institute of Allergy and Infectious Diseases, Bethesda, Md.

“Given the rate of infection that’s going on in this country, and the distribution of the clinical trial sites involving tens of thousands of volunteers, we project that we will have an answer as to whether or not we have a safe and effective vaccine by November or December,” Dr. Fauci said today in his virtual keynote address during the annual meeting of the American College of Chest Physicians.

“It may come earlier -- this month, in October,” he added in his remarks. “That is unlikely – it is more likely that we’ll have an answer in November and December.”

If that timing does come to pass, Dr. Fauci said, it’s possible that distribution of doses could start at the end of the year, continuing throughout the beginning and middle of 2021.

Although there are no guarantees, Dr. Fauci said he is “cautiously optimistic” regarding the timeline.

He said that his optimism is based in part on animal studies and phase 1 data that demonstrate robust neutralizing antibody responses to a vaccine that are equivalent to, if not greater than, natural infection with the SARS-CoV-2 virus that causes COVID-19.

Rapid development gives reason for hope

Ryan C. Maves, MD, FCCP, a critical care and infectious disease specialist at Naval Medical Center San Diego, said there is reason to be hopeful that a vaccine will be available by the end of the calendar year. He cautioned, however, that this timing is based on the assumption that one of the vaccines will be proven safe and effective very soon.

“We’re lucky to have multiple phase 3 trials using multiple vaccine technologies in different platforms,” Dr. Maves said in a panel discussion following Dr. Fauci’s remarks. “I think the odds are very high that one of them will be effective.”

“I’m hoping that multiple vaccines will be effective,” Dr. Maves added. “Then we’ll be in a good position of determining which is the best of several good options, as a society and as a world.”

COVID-19 vaccine development over the past year has been remarkably fast, especially given the previous record set by the mumps vaccine, which took about four years to go from initial steps to rollout, Dr. Maves noted.

Dr. Fauci said the federal government has taken a “strategic approach” to the COVID-19 vaccine that includes direct involvement in the research and development of six different vaccine candidates, five of which are now in phase 3 trials.

As part of that strategic approach, the study protocols are harmonized to have a common data and safety monitoring board, common primary and secondary endpoints, and an independent statistical group to determine correlates of protection, Dr. Fauci said.

Prioritizing COVID-19 vaccine distribution

Who gets COVID-19 vaccine first will be a challenge for governmental organizations as well as bioethicists, who have proposed different strategies for fairly prioritizing different groups for access.

Reaching communities of color will be an important consideration for prioritization, according to Dr. Maves, given the disproportionate burden of disease on Black and Hispanic individuals, among other such populations.

COVID-19–related hospitalization rates have been substantially higher in communities of color, Dr. Fauci said in his keynote address. Age-adjusted hospitalization rates for Hispanic/Latinx and Black populations are 375 to 368 per 100,000, respectively, compared with just 82 per 100,000 for White non-Hispanics, according to data from the Centers for Disease Control and Prevention.

Outreach to those communities should include building trust in those populations that they will benefit from a safe and effective vaccine, and making sure that the vaccine is available to those communities as quickly as possible, Dr. Maves said.

Dr. Fauci and Dr. Maves provided no disclosures related to their presentations.

[email protected]

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

A version of this article originally appeared on Medscape.com.

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

A version of this article originally appeared on Medscape.com.

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

A version of this article originally appeared on Medscape.com.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

The U.S. Food and Drug Administration released new warnings Oct. 15 that most nonsteroidal anti-inflammatory agents (NSAIDs) carry an elevated risk for kidney complications in unborn children when taken around weeks 20 or later in pregnancy.

Citing newly available research, the agency states the risk of low amniotic fluid (known as oligohydramnios) can occur, which in turn can cause rare but serious kidney problems in the offspring. Pregnancy complications also can result.

The FDA action expands on earlier warnings about agents in this drug class, which the FDA previously cautioned about taking after week 30 of pregnancy because of heart-related risks.

Manufacturers of both over-the-counter and prescription NSAIDs – including ibuprofen, naproxen, diclofenac, and celecoxib – will be required to update their labeling with the new warning.

Low-dose (81-mg) aspirin is excluded from this warning.

“Low-dose aspirin may be an important treatment for some women during pregnancy and should be taken under the direction of a healthcare professional,” the agency stated in a news release.

“It is important that women understand the benefits and risks of the medications they may take over the course of their pregnancy,” Patrizia Cavazzoni, MD, acting director of FDA’s Center for Drug Evaluation and Research, states in the release. “To this end, the agency is using its regulatory authority to inform women and their healthcare providers about the risks if NSAIDs are used after around 20 weeks of pregnancy and beyond.”

Oligohydramnios can arise quickly – in as little as 2 days – or weeks after starting regular NSAID use in this patient population. The condition usually resolves if a pregnant woman stops taking the NSAID, the agency notes.

If a health care provider believes NSAIDs are necessary between about 20 and 30 weeks of pregnancy, use should be limited to the lowest effective dose and shortest duration possible, the Drug Safety Communication notes.

As a reminder, health care professionals and patients should report side effects from NSAIDs to the FDA’s MedWatch program.

A version of this article originally appeared on Medscape.com.

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

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

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

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

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

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

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.

Upadacitinib (Rinvoq) proved superior to abatacept in both disease activity and remission in rheumatoid arthritis patients yet led to more adverse events, according to a new study that compared the two drugs.

“Additional data from longer and larger trials are needed to better understand long-term outcomes and safety of upadacitinib as compared with other drugs for the treatment of rheumatoid arthritis,” wrote Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen in St. Gallen, Switzerland, and her colleagues. The study was published in the New England Journal of Medicine.

The Food and Drug Administration approved upadacitinib for the treatment of rheumatoid arthritis in August 2019.

To compare the Janus kinase (JAK) inhibitor upadacitinib and the biologic disease-modifying antirheumatic drug (DMARD) abatacept as safe and effective treatments for RA, the researchers launched a randomized, double-blind, phase 3 clinical trial dubbed SELECT-CHOICE at 120 sites in 28 countries. All patients had moderate to severe active disease after previously having inadequate responses to at least one biologic DMARD. Slightly more than 82% of the participants were female, with a mean age of 55 years and mean RA duration of 12 years.

Patients were assigned either 15 mg of oral upadacitinib daily (n = 303) or intravenous abatacept at day 1 and weeks 2, 4, 8, 12, 16 and 20 (n = 309) with dosage tied to body weight, each in combination with stable synthetic DMARDs. Disease activity was measured after 12 weeks via the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP). A DAS28-CRP of more than 5.1 was categorized as high disease activity, while 3.2-5.1 meant moderate disease activity, 2.6-3.2 meant low disease activity, and less than 2.6 indicated remission.

The mean DAS28-CRP at baseline was 5.70 in the upadacitinib group and 5.88 in the abatacept group. After 12 weeks, the mean change from baseline was –2.52 points and –2.00 points, respectively (difference, –0.52 points; 95% confidence interval, –0.69 to –0.35; P < .001 for noninferiority; P < .001 for superiority). In patients with a DAS28-CRP of less than 2.6, the percentage of those having remission was 30% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P < .001 for superiority).

Over the 24-week trial period, the incidence of all adverse events (209 vs. 189) and serious adverse events (10 vs. 5) was higher in the upadacitinib group than in the abatacept group. There were 23 cases of hepatic disorder with upadacitinib, compared with 5 with abatacept; 2 thromboembolic events with upadacitinib, compared with 0 with abatacept; and 2 deaths with upadacitinib, compared with 1 with abatacept.

“The thing that bothers me, actually, is the adverse events,” Daniel E. Furst, MD, professor of medicine (emeritus) and rheumatology at the University of California, Los Angeles, said in an interview. “There were a fair number of them, all of which were a little higher in upadacitinib. They certainly made very little of those.”

He noted several other concerns about the study, including a potential geographic effect stemming from 60% of the study’s centers being in South and Central America and Eastern Europe. “Those patients don’t always have very good medical care,” he said. “They have an inherent, underlying placebo response that can be much different than Western Europe and North America.”

He also questioned their choice of primary endpoint metric.

“I think a much more legitimate way at looking at remission is the CDAI [Clinical Disease Activity Index] rather than the DAS28,” he said. “The DAS28, even at its best, is low disease activity, not true remission.”

“Bottom line,” he added, “this is a legitimate study that supports previous findings. One more important thing that is overlooked, though, is an economic analysis. A true economic analysis would be very important to place this in the armamentarium.”
 

Study affirms upadacitinib’s place in the RA treatment pecking order

By showing that upadacitinib was not only noninferior but superior to abatacept in decreasing disease activity, Rubbert-Roth and colleagues have positioned the JAK inhibitor at “the forefront of treatment for rheumatoid arthritis,” wrote Guro L. Goll, MD, PhD, and Tore K. Kvien, MD, PhD, of Diakonhjemmet Hospital in Oslo, in an accompanying editorial.

Though the authors noted that the 24-week trial was likely too short to make meaningful assumptions about long-term outcomes, they recognized the notably improved treatment outcomes over the study period and stated the importance of “head-to-head trials ... to inform evidence-based clinical decisions.” Similar to Dr. Furst, however, they stated an interest in “detailed data on changes in the CDAI score as a continuous measure.”

They also acknowledged the significant increase in adverse events among patients in the upadacitinib group, underlining the need to learn more in forthcoming, lengthier trials. “Rheumatologists will be looking hard at future data,” they wrote, “to assess whether improved treatment outcomes justify an increased risk of adverse events.”

The study was supported by AbbVie. The authors acknowledged numerous potential conflicts of interest, including receiving research grants and fees from various pharmaceutical companies for consulting, lectures, and being on advisory boards.

SOURCE: Rubbert-Roth A et al. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2008250.