MDedge Rheumatology

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.

Anatoliy Sizov/Getty Images

Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.

CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.

In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).

The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.

Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.

Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).

The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.

The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.

The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.

The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.

Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.

Anatoliy Sizov/Getty Images

Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.

CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.

In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).

The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.

Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.

Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).

The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.

The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.

The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.

The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.

Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.

Anatoliy Sizov/Getty Images

Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.

CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.

In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).

The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.

Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.

Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).

The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.

The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.

The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.

The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.

Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.

“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”

Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.

The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.

Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.

In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”

The authors had no outside funding for the study and had no potential conflicts of interest to disclose.

[email protected]

Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.

“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”

Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.

The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.

Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.

In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”

The authors had no outside funding for the study and had no potential conflicts of interest to disclose.

[email protected]

Patients with rheumatoid arthritis in remission had a rate of flare following vaccination with the Pfizer/BioNtech COVID-19 vaccine that appears to be on par with rates seen with other vaccines in patients with RA, according to results from a small Italian cohort study.

“Our data show a very low flare rate [7.8% (6 of 77)] after the BNT162b2 COVID-19 vaccine in patients with RA in remission and are consistent with previous findings about varicella-zoster virus (6.7%) and hepatitis B virus (2.2%) vaccinations,” Riccardo Bixio, MD, and colleagues from University of Verona (Italy) Hospital Trust wrote in ACR Open Rheumatology. “Because remission is not commonly obtained in the real world, we are aware that our findings may not be generalizable to all patients with RA receiving COVID-19 vaccination.”

Other studies of flare rate after COVID-19 vaccination in patients with a variety of rheumatic and musculoskeletal diseases have reported rates ranging from 5% to 17%, they said.

The 77 consecutive patients from the University of Verona center that conducted the study were all in clinical remission in the 3 months before vaccination based on a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) of less than 2.6, and all had discontinued antirheumatic therapies according to American College of Rheumatology COVID-19 recommendations. The researchers defined flares as agreement between patient and rheumatologist assessments and a DAS28-CRP increase of more than 1.2.

Five of the six people with a flare had it occur after the second dose at a mean of 2.6 days later, and all flares were resolved within 2 weeks using glucocorticoids with or without anti-inflammatory drugs. One flare was called severe. The overall disease activity of the cohort after 3 months was not significantly changed after vaccination.

In noting that five out of the six patients with flares had withdrawn or delayed antirheumatic therapies around the time of vaccination according to ACR recommendations, the authors wrote that “Even if there is no direct evidence that holding therapies could occur in a higher proportion of disease flares, we suggest that clinicians consider this possibility when counseling patients about COVID-19 vaccination.”

The authors had no outside funding for the study and had no potential conflicts of interest to disclose.

[email protected]

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

A version of this article first appeared on WebMD.com.

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

A version of this article first appeared on WebMD.com.

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

A version of this article first appeared on WebMD.com.

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

A version of this article first appeared on WebMD.com.

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

A version of this article first appeared on WebMD.com.

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

A version of this article first appeared on WebMD.com.

Although breakthrough COVID-19 infections appear to be infrequent in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), these patients’ comparatively low antibodies after their initial vaccine series validate the recommendation that booster doses could reinforce their immune responses. These findings were highlighted in three letters recently published in Annals of the Rheumatic Diseases.

In the first letter, the researchers assessed breakthrough COVID-19 infections among vaccinated patients with iRMDs who were treated within the Mass General Brigham health care system in the Boston area. Of the 340 COVID-19 infections in patients with iRMDs after vaccinations were approved by the Food and Drug Administration for emergency use, 16 (4.7%) were breakthrough infections. All but one of the breakthrough infections were symptomatic, and six of the patients were hospitalized.

Patients who had breakthrough infections took disease-modifying antirheumatic drugs (DMARDs) that included rituximab and glucocorticoids (five patients each), mycophenolate mofetil or mycophenolic acid (four patients), and methotrexate (three patients). Two of the patients died, both of whom were on rituximab and had interstitial lung disease.

“Some DMARD users may require alternative risk-mitigation strategies, including passive immunity or booster vaccines, and may need to continue shielding practices,” the authors wrote.

“Honestly, it’s hard to know what to make of that rate of breakthrough infections,” Camille Kotton, MD, clinical director of transplant and immunocompromised host infectious diseases in the infectious diseases division at Massachusetts General Hospital in Boston, said in an interview. “People who are immunocompromised were strongly advised to change behavior so as to avoid infection, which probably greatly alters their risk of breakthrough infection. It’s thus hard to evaluate vaccine efficacy.

“Also, 93% were symptomatic, which is fairly high,” she added. “I’m not sure if these patients were more likely to be symptomatic or if there was some bias in testing based on symptoms.”

In the second letter, the researchers assessed postvaccination COVID-19 infections in European patients with iRMDs. Two COVID-19 registries with thousands of patients were reviewed, with less than 1% of patients in each deemed eligible for this study. Of the 34 patients who were ultimately analyzed with available COVID-19 outcomes – 10 were fully vaccinated and 24 were partially vaccinated – 28 fully recovered, 3 recovered with ongoing sequelae, and 3 patients died. The three patients who died were all over 70 years old and had been treated with glucocorticoids and mycophenolate mofetil, glucocorticoids, and rituximab, respectively.

The medications most frequently used by the iRMDs patients with breakthrough cases included glucocorticoids (32%), methotrexate (26%), and tumor necrosis factor inhibitors (26%).

“Overall, the low numbers of SARS-CoV-2 infection post vaccination in both registries are encouraging,” the authors wrote, adding that “all three deceased patients were treated with medications that are potential negative influences on postvaccination SARS-CoV-2 immunogenicity in the RMD population.”
 

Patients with RMDs: Consider COVID-19 booster shots

In the third letter, the researchers investigated booster doses of COVID-19 vaccine in patients with autoimmune diseases. Of the 18 participants who received a booster dose, 14 were on antimetabolite therapy and 8 of those were on mycophenolate. At a median of 29 days after completion of their initial vaccine series, antispike antibodies were negative in 10 of the participants and low positive in 6 others, with a median antispike antibody level of less than 0.4 U/mL (interquartile range, <0.4-222 U/mL).

Booster doses were administered at a median of 77 days after completion of the initial series. At a median of 30 days after booster dose, 89% of the participants had an augmented humoral response, with a median antispike antibody level of 2,500 (IQR, 885-2,500 U/mL). Of the 10 participants who had negative anti-spike antibodies after the initial series, 80% were positive after the booster.

“I think this study supports the wealth of evidence that contributed to the [Centers for Disease Control and Prevention]’s and the FDA’s recommendation to get the third dose of the COVID vaccination,” coauthor Julie J. Paik, MD, of Johns Hopkins University, Baltimore, said in an interview. “Our patients are a very vulnerable group, including lupus patients or myositis patients, both of whom can get severe COVID if they were to contract it. They think they’re protected after a two-dose series, but in reality they’re not.

“We were just happy that they had a response,” she added. “Most of them had absolutely no response whatsoever after the first series.”

One other recently published case report in Arthritis & Rheumatology describes booster vaccination with the viral vector Johnson & Johnson vaccine in a man with seropositive RA who had previously received both doses of the Moderna mRNA-1273 vaccine. The 74-year-old man, who had low disease activity over the past 5 years on hydroxychloroquine, etanercept, and leflunomide, received the booster dose of his own accord after undergoing testing that showed a semiquantitative spike protein receptor binding domain (RBD) antibody level of 53.9 U/mL (reference range, 0-2,500 U/mL) and a negative SARS-CoV-2 antispike (S1/RBD) IgG test, as well as less than 10% blocking activity on an assay designed to detect blocking of the interaction between the SARS-CoV-2 spike protein RBD and the human ACE2 receptor and a negative interferon-gamma release assay detecting SARS-CoV-2–specific T cells. Several weeks after the booster dose, a repeat semiquantitative spike protein RBD antibody level was 2,455.0 U/mL and the S1/RBD IgG level was positive. An ACE2 blocking assay demonstrated 90%-100% blocking activity, but the interferon-gamma release assay remained negative.

“I would recommend abiding by the CDC guidelines regarding boosters for immunocompromised patients,” Dr. Kotton stated. “Patients with rheumatologic disease generally fit into the last category on that list. We don’t have an antibody titer that ensures protection, and as per CDC guidance, we don’t recommend checking antibody titers. Furthermore, boosters were given for this study before the CDC recommendation came out.”

Dr. Paik and coauthors acknowledged their study’s limitations, including a small, inhomogeneous sample and a lack of data on memory B-cell and T-cell response. They also echoed Dr. Kotton’s thoughts by noting that, although this subset of patients had notably limited antibody responses, “no antibody titer has been defined to correlate with protection.”

“Of course, the humoral response isn’t the whole story,” Dr. Paik said. “Some studies are showing that some vaccine recipients may not have the antibodies but their T-cell response may still be intact; it just takes time, and we’re not picking it up. Even if the antibody test is coming up negative, there may be some immunogenicity to the vaccine that we’re not detecting.

“Hopefully at some point, we’ll have more T-cell immunophenotyping to provide better insight into the full vaccine response.”

The Boston-area breakthrough study and the booster shot study were both funded primarily by grants from various institutes within the National Institutes of Health. The European study was financially supported by the European Alliance of Associations for Rheumatology.

Although breakthrough COVID-19 infections appear to be infrequent in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), these patients’ comparatively low antibodies after their initial vaccine series validate the recommendation that booster doses could reinforce their immune responses. These findings were highlighted in three letters recently published in Annals of the Rheumatic Diseases.

In the first letter, the researchers assessed breakthrough COVID-19 infections among vaccinated patients with iRMDs who were treated within the Mass General Brigham health care system in the Boston area. Of the 340 COVID-19 infections in patients with iRMDs after vaccinations were approved by the Food and Drug Administration for emergency use, 16 (4.7%) were breakthrough infections. All but one of the breakthrough infections were symptomatic, and six of the patients were hospitalized.

Patients who had breakthrough infections took disease-modifying antirheumatic drugs (DMARDs) that included rituximab and glucocorticoids (five patients each), mycophenolate mofetil or mycophenolic acid (four patients), and methotrexate (three patients). Two of the patients died, both of whom were on rituximab and had interstitial lung disease.

“Some DMARD users may require alternative risk-mitigation strategies, including passive immunity or booster vaccines, and may need to continue shielding practices,” the authors wrote.

“Honestly, it’s hard to know what to make of that rate of breakthrough infections,” Camille Kotton, MD, clinical director of transplant and immunocompromised host infectious diseases in the infectious diseases division at Massachusetts General Hospital in Boston, said in an interview. “People who are immunocompromised were strongly advised to change behavior so as to avoid infection, which probably greatly alters their risk of breakthrough infection. It’s thus hard to evaluate vaccine efficacy.

“Also, 93% were symptomatic, which is fairly high,” she added. “I’m not sure if these patients were more likely to be symptomatic or if there was some bias in testing based on symptoms.”

In the second letter, the researchers assessed postvaccination COVID-19 infections in European patients with iRMDs. Two COVID-19 registries with thousands of patients were reviewed, with less than 1% of patients in each deemed eligible for this study. Of the 34 patients who were ultimately analyzed with available COVID-19 outcomes – 10 were fully vaccinated and 24 were partially vaccinated – 28 fully recovered, 3 recovered with ongoing sequelae, and 3 patients died. The three patients who died were all over 70 years old and had been treated with glucocorticoids and mycophenolate mofetil, glucocorticoids, and rituximab, respectively.

The medications most frequently used by the iRMDs patients with breakthrough cases included glucocorticoids (32%), methotrexate (26%), and tumor necrosis factor inhibitors (26%).

“Overall, the low numbers of SARS-CoV-2 infection post vaccination in both registries are encouraging,” the authors wrote, adding that “all three deceased patients were treated with medications that are potential negative influences on postvaccination SARS-CoV-2 immunogenicity in the RMD population.”
 

Patients with RMDs: Consider COVID-19 booster shots

In the third letter, the researchers investigated booster doses of COVID-19 vaccine in patients with autoimmune diseases. Of the 18 participants who received a booster dose, 14 were on antimetabolite therapy and 8 of those were on mycophenolate. At a median of 29 days after completion of their initial vaccine series, antispike antibodies were negative in 10 of the participants and low positive in 6 others, with a median antispike antibody level of less than 0.4 U/mL (interquartile range, <0.4-222 U/mL).

Booster doses were administered at a median of 77 days after completion of the initial series. At a median of 30 days after booster dose, 89% of the participants had an augmented humoral response, with a median antispike antibody level of 2,500 (IQR, 885-2,500 U/mL). Of the 10 participants who had negative anti-spike antibodies after the initial series, 80% were positive after the booster.

“I think this study supports the wealth of evidence that contributed to the [Centers for Disease Control and Prevention]’s and the FDA’s recommendation to get the third dose of the COVID vaccination,” coauthor Julie J. Paik, MD, of Johns Hopkins University, Baltimore, said in an interview. “Our patients are a very vulnerable group, including lupus patients or myositis patients, both of whom can get severe COVID if they were to contract it. They think they’re protected after a two-dose series, but in reality they’re not.

“We were just happy that they had a response,” she added. “Most of them had absolutely no response whatsoever after the first series.”

One other recently published case report in Arthritis & Rheumatology describes booster vaccination with the viral vector Johnson & Johnson vaccine in a man with seropositive RA who had previously received both doses of the Moderna mRNA-1273 vaccine. The 74-year-old man, who had low disease activity over the past 5 years on hydroxychloroquine, etanercept, and leflunomide, received the booster dose of his own accord after undergoing testing that showed a semiquantitative spike protein receptor binding domain (RBD) antibody level of 53.9 U/mL (reference range, 0-2,500 U/mL) and a negative SARS-CoV-2 antispike (S1/RBD) IgG test, as well as less than 10% blocking activity on an assay designed to detect blocking of the interaction between the SARS-CoV-2 spike protein RBD and the human ACE2 receptor and a negative interferon-gamma release assay detecting SARS-CoV-2–specific T cells. Several weeks after the booster dose, a repeat semiquantitative spike protein RBD antibody level was 2,455.0 U/mL and the S1/RBD IgG level was positive. An ACE2 blocking assay demonstrated 90%-100% blocking activity, but the interferon-gamma release assay remained negative.

“I would recommend abiding by the CDC guidelines regarding boosters for immunocompromised patients,” Dr. Kotton stated. “Patients with rheumatologic disease generally fit into the last category on that list. We don’t have an antibody titer that ensures protection, and as per CDC guidance, we don’t recommend checking antibody titers. Furthermore, boosters were given for this study before the CDC recommendation came out.”

Dr. Paik and coauthors acknowledged their study’s limitations, including a small, inhomogeneous sample and a lack of data on memory B-cell and T-cell response. They also echoed Dr. Kotton’s thoughts by noting that, although this subset of patients had notably limited antibody responses, “no antibody titer has been defined to correlate with protection.”

“Of course, the humoral response isn’t the whole story,” Dr. Paik said. “Some studies are showing that some vaccine recipients may not have the antibodies but their T-cell response may still be intact; it just takes time, and we’re not picking it up. Even if the antibody test is coming up negative, there may be some immunogenicity to the vaccine that we’re not detecting.

“Hopefully at some point, we’ll have more T-cell immunophenotyping to provide better insight into the full vaccine response.”

The Boston-area breakthrough study and the booster shot study were both funded primarily by grants from various institutes within the National Institutes of Health. The European study was financially supported by the European Alliance of Associations for Rheumatology.

Although breakthrough COVID-19 infections appear to be infrequent in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), these patients’ comparatively low antibodies after their initial vaccine series validate the recommendation that booster doses could reinforce their immune responses. These findings were highlighted in three letters recently published in Annals of the Rheumatic Diseases.

In the first letter, the researchers assessed breakthrough COVID-19 infections among vaccinated patients with iRMDs who were treated within the Mass General Brigham health care system in the Boston area. Of the 340 COVID-19 infections in patients with iRMDs after vaccinations were approved by the Food and Drug Administration for emergency use, 16 (4.7%) were breakthrough infections. All but one of the breakthrough infections were symptomatic, and six of the patients were hospitalized.

Patients who had breakthrough infections took disease-modifying antirheumatic drugs (DMARDs) that included rituximab and glucocorticoids (five patients each), mycophenolate mofetil or mycophenolic acid (four patients), and methotrexate (three patients). Two of the patients died, both of whom were on rituximab and had interstitial lung disease.

“Some DMARD users may require alternative risk-mitigation strategies, including passive immunity or booster vaccines, and may need to continue shielding practices,” the authors wrote.

“Honestly, it’s hard to know what to make of that rate of breakthrough infections,” Camille Kotton, MD, clinical director of transplant and immunocompromised host infectious diseases in the infectious diseases division at Massachusetts General Hospital in Boston, said in an interview. “People who are immunocompromised were strongly advised to change behavior so as to avoid infection, which probably greatly alters their risk of breakthrough infection. It’s thus hard to evaluate vaccine efficacy.

“Also, 93% were symptomatic, which is fairly high,” she added. “I’m not sure if these patients were more likely to be symptomatic or if there was some bias in testing based on symptoms.”

In the second letter, the researchers assessed postvaccination COVID-19 infections in European patients with iRMDs. Two COVID-19 registries with thousands of patients were reviewed, with less than 1% of patients in each deemed eligible for this study. Of the 34 patients who were ultimately analyzed with available COVID-19 outcomes – 10 were fully vaccinated and 24 were partially vaccinated – 28 fully recovered, 3 recovered with ongoing sequelae, and 3 patients died. The three patients who died were all over 70 years old and had been treated with glucocorticoids and mycophenolate mofetil, glucocorticoids, and rituximab, respectively.

The medications most frequently used by the iRMDs patients with breakthrough cases included glucocorticoids (32%), methotrexate (26%), and tumor necrosis factor inhibitors (26%).

“Overall, the low numbers of SARS-CoV-2 infection post vaccination in both registries are encouraging,” the authors wrote, adding that “all three deceased patients were treated with medications that are potential negative influences on postvaccination SARS-CoV-2 immunogenicity in the RMD population.”
 

Patients with RMDs: Consider COVID-19 booster shots

In the third letter, the researchers investigated booster doses of COVID-19 vaccine in patients with autoimmune diseases. Of the 18 participants who received a booster dose, 14 were on antimetabolite therapy and 8 of those were on mycophenolate. At a median of 29 days after completion of their initial vaccine series, antispike antibodies were negative in 10 of the participants and low positive in 6 others, with a median antispike antibody level of less than 0.4 U/mL (interquartile range, <0.4-222 U/mL).

Booster doses were administered at a median of 77 days after completion of the initial series. At a median of 30 days after booster dose, 89% of the participants had an augmented humoral response, with a median antispike antibody level of 2,500 (IQR, 885-2,500 U/mL). Of the 10 participants who had negative anti-spike antibodies after the initial series, 80% were positive after the booster.

“I think this study supports the wealth of evidence that contributed to the [Centers for Disease Control and Prevention]’s and the FDA’s recommendation to get the third dose of the COVID vaccination,” coauthor Julie J. Paik, MD, of Johns Hopkins University, Baltimore, said in an interview. “Our patients are a very vulnerable group, including lupus patients or myositis patients, both of whom can get severe COVID if they were to contract it. They think they’re protected after a two-dose series, but in reality they’re not.

“We were just happy that they had a response,” she added. “Most of them had absolutely no response whatsoever after the first series.”

One other recently published case report in Arthritis & Rheumatology describes booster vaccination with the viral vector Johnson & Johnson vaccine in a man with seropositive RA who had previously received both doses of the Moderna mRNA-1273 vaccine. The 74-year-old man, who had low disease activity over the past 5 years on hydroxychloroquine, etanercept, and leflunomide, received the booster dose of his own accord after undergoing testing that showed a semiquantitative spike protein receptor binding domain (RBD) antibody level of 53.9 U/mL (reference range, 0-2,500 U/mL) and a negative SARS-CoV-2 antispike (S1/RBD) IgG test, as well as less than 10% blocking activity on an assay designed to detect blocking of the interaction between the SARS-CoV-2 spike protein RBD and the human ACE2 receptor and a negative interferon-gamma release assay detecting SARS-CoV-2–specific T cells. Several weeks after the booster dose, a repeat semiquantitative spike protein RBD antibody level was 2,455.0 U/mL and the S1/RBD IgG level was positive. An ACE2 blocking assay demonstrated 90%-100% blocking activity, but the interferon-gamma release assay remained negative.

“I would recommend abiding by the CDC guidelines regarding boosters for immunocompromised patients,” Dr. Kotton stated. “Patients with rheumatologic disease generally fit into the last category on that list. We don’t have an antibody titer that ensures protection, and as per CDC guidance, we don’t recommend checking antibody titers. Furthermore, boosters were given for this study before the CDC recommendation came out.”

Dr. Paik and coauthors acknowledged their study’s limitations, including a small, inhomogeneous sample and a lack of data on memory B-cell and T-cell response. They also echoed Dr. Kotton’s thoughts by noting that, although this subset of patients had notably limited antibody responses, “no antibody titer has been defined to correlate with protection.”

“Of course, the humoral response isn’t the whole story,” Dr. Paik said. “Some studies are showing that some vaccine recipients may not have the antibodies but their T-cell response may still be intact; it just takes time, and we’re not picking it up. Even if the antibody test is coming up negative, there may be some immunogenicity to the vaccine that we’re not detecting.

“Hopefully at some point, we’ll have more T-cell immunophenotyping to provide better insight into the full vaccine response.”

The Boston-area breakthrough study and the booster shot study were both funded primarily by grants from various institutes within the National Institutes of Health. The European study was financially supported by the European Alliance of Associations for Rheumatology.

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.

“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.

The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).

The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
 

Mortality from opioid-associated cardiac arrest is lower

These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.

When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.

While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.

Rate of opioid-associated cardiac arrests underestimated

In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.

For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.

In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.

In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
 

Patterns of opioid-induced cardiac arrests evolving

The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.

Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.

“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.

He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.

“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.

In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.

Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.

Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.

Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.

“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.

The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).

The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
 

Mortality from opioid-associated cardiac arrest is lower

These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.

When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.

While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.

Rate of opioid-associated cardiac arrests underestimated

In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.

For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.

In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.

In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
 

Patterns of opioid-induced cardiac arrests evolving

The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.

Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.

“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.

He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.

“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.

In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.

Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.

Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.

Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.

“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.

The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).

The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
 

Mortality from opioid-associated cardiac arrest is lower

These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.

When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.

While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.

Rate of opioid-associated cardiac arrests underestimated

In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.

For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.

In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.

In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
 

Patterns of opioid-induced cardiac arrests evolving

The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.

Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.

“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.

He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.

“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.

In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.

Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.

Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

A version of this article first appeared on WebMD.com.
 

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

A version of this article first appeared on WebMD.com.
 

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

A version of this article first appeared on WebMD.com.