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TNF inhibitor plus methotrexate surpassed methotrexate monotherapy in PsA
Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.
After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
“It’s a well-known fact that adalimumab is more effective than methotrexate in [PsA] patients who do not respond sufficiently well to methotrexate. Patients failing on methotrexate have been escalated to a TNF inhibitor for years,” commented Robert B.M. Landewé, MD, a rheumatologist and professor of medicine at the University of Amsterdam, and a coauthor of the EULAR PsA treatment recommendations. “In the Netherlands and in my practice, every [PsA] patient starts on methotrexate until a dosage of at least 15 mg/week, but if they don’t have sufficient response we escalate to adding a TNF inhibitor,” he said in an interview. “A significant proportion of patients with PsA respond well to moderate to higher dosages of methotrexate,” and this monotherapy with escalation of methotrexate can be safely continued for more than 3 months in many patients without the risk of “losing too much time by waiting” to start a bDMARD.
Dr. Coates said that her practice was to look for some level of response to methotrexate by 12 weeks on treatment and for achievement of minimal disease activity within 24 weeks of treatment. If these targets are not reached, she then adds a TNF inhibitor.
The CONTROL study ran at 60 sites in the United States and in 12 other countries and enrolled patients with active PsA despite treatment with methotrexate for at least 4 weeks and no history of treatment with a bDMARD. Patients received either 40 mg adalimumab every other week plus 15 mg of methotrexate weekly, or maximum-tolerated methotrexate up to 25 mg/week. The results also showed that the primary endpoint of the rate of achieved minimal disease activity seen overall in each of the two study arms was consistent in both the roughly half of patients who had been on methotrexate monotherapy for 3 months or less before entering the study as well as those who had been on initial methotrexate monotherapy for a longer period. Other secondary endpoints examined also showed significantly better responses to adding adalimumab, including a tripling of the rate at which patients achieved complete resolution of their Psoriasis Area and Severity Index score, which occurred in 30% of patients on the TNF inhibitor plus methotrexate and in 9% of those on methotrexate monotherapy.
The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.
“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”
CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.
SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.
Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.
After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
“It’s a well-known fact that adalimumab is more effective than methotrexate in [PsA] patients who do not respond sufficiently well to methotrexate. Patients failing on methotrexate have been escalated to a TNF inhibitor for years,” commented Robert B.M. Landewé, MD, a rheumatologist and professor of medicine at the University of Amsterdam, and a coauthor of the EULAR PsA treatment recommendations. “In the Netherlands and in my practice, every [PsA] patient starts on methotrexate until a dosage of at least 15 mg/week, but if they don’t have sufficient response we escalate to adding a TNF inhibitor,” he said in an interview. “A significant proportion of patients with PsA respond well to moderate to higher dosages of methotrexate,” and this monotherapy with escalation of methotrexate can be safely continued for more than 3 months in many patients without the risk of “losing too much time by waiting” to start a bDMARD.
Dr. Coates said that her practice was to look for some level of response to methotrexate by 12 weeks on treatment and for achievement of minimal disease activity within 24 weeks of treatment. If these targets are not reached, she then adds a TNF inhibitor.
The CONTROL study ran at 60 sites in the United States and in 12 other countries and enrolled patients with active PsA despite treatment with methotrexate for at least 4 weeks and no history of treatment with a bDMARD. Patients received either 40 mg adalimumab every other week plus 15 mg of methotrexate weekly, or maximum-tolerated methotrexate up to 25 mg/week. The results also showed that the primary endpoint of the rate of achieved minimal disease activity seen overall in each of the two study arms was consistent in both the roughly half of patients who had been on methotrexate monotherapy for 3 months or less before entering the study as well as those who had been on initial methotrexate monotherapy for a longer period. Other secondary endpoints examined also showed significantly better responses to adding adalimumab, including a tripling of the rate at which patients achieved complete resolution of their Psoriasis Area and Severity Index score, which occurred in 30% of patients on the TNF inhibitor plus methotrexate and in 9% of those on methotrexate monotherapy.
The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.
“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”
CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.
SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.
Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.
After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.
The findings are “supportive of the EULAR recommendations” for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and “inadequate response to at least one [conventional synthetic] DMARD,” such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). “A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It’s a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently,” Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
“It’s a well-known fact that adalimumab is more effective than methotrexate in [PsA] patients who do not respond sufficiently well to methotrexate. Patients failing on methotrexate have been escalated to a TNF inhibitor for years,” commented Robert B.M. Landewé, MD, a rheumatologist and professor of medicine at the University of Amsterdam, and a coauthor of the EULAR PsA treatment recommendations. “In the Netherlands and in my practice, every [PsA] patient starts on methotrexate until a dosage of at least 15 mg/week, but if they don’t have sufficient response we escalate to adding a TNF inhibitor,” he said in an interview. “A significant proportion of patients with PsA respond well to moderate to higher dosages of methotrexate,” and this monotherapy with escalation of methotrexate can be safely continued for more than 3 months in many patients without the risk of “losing too much time by waiting” to start a bDMARD.
Dr. Coates said that her practice was to look for some level of response to methotrexate by 12 weeks on treatment and for achievement of minimal disease activity within 24 weeks of treatment. If these targets are not reached, she then adds a TNF inhibitor.
The CONTROL study ran at 60 sites in the United States and in 12 other countries and enrolled patients with active PsA despite treatment with methotrexate for at least 4 weeks and no history of treatment with a bDMARD. Patients received either 40 mg adalimumab every other week plus 15 mg of methotrexate weekly, or maximum-tolerated methotrexate up to 25 mg/week. The results also showed that the primary endpoint of the rate of achieved minimal disease activity seen overall in each of the two study arms was consistent in both the roughly half of patients who had been on methotrexate monotherapy for 3 months or less before entering the study as well as those who had been on initial methotrexate monotherapy for a longer period. Other secondary endpoints examined also showed significantly better responses to adding adalimumab, including a tripling of the rate at which patients achieved complete resolution of their Psoriasis Area and Severity Index score, which occurred in 30% of patients on the TNF inhibitor plus methotrexate and in 9% of those on methotrexate monotherapy.
The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that’s an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.
“We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug,” Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor “are far better” than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab “may induce aggravation of PsA in a significant number of patients.”
CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.
SOURCE: Coates LC et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33, Abstract OP0050.
FROM EULAR 2020 E-CONGRESS
JAK inhibitors have top risk for herpes zoster among newer RA DMARDs
Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.
These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.
The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.
Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.
“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.
“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.
Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).
Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.
“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.
“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).
Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”
Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”
Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.
Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.
“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.
The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.
SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.
Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.
These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.
The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.
Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.
“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.
“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.
Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).
Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.
“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.
“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).
Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”
Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”
Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.
Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.
“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.
The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.
SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.
Patients with rheumatoid arthritis (RA) who are treated with Janus kinase (JAK) inhibitors had the highest risk of developing herpes zoster among newer disease-modifying antirheumatic drugs (DMARDs), according to data released from the German biologics registry.
These are believed to be the first European data on the risk of herpes zoster with JAK inhibitors and showed that the crude incidence rate of herpes zoster per 1,000 patient-years was 24.9 with JAK inhibitors, compared with just 5.8 for controls taking conventional synthetic (cs) DMARDs.
The risk of herpes zoster was also increased with other biologic (b) and targeted synthetic (ts) DMARDs that were assessed, with crude rates per 1,000 patient-years of 10.4 for monoclonal tumor necrosis factor inhibitors (TNFi), 10.5 for B-cell targeted therapies, 9.4 for T-cell costimulation modulators, 9.0 for soluble TNF receptors, and 8.5 for interleukin (IL)-6 inhibitors.
Overall, JAK inhibitor treatment was associated with a fivefold higher risk of herpes zoster (hazard ratio, 5.0; P < .0001), compared with the control csDMARD population after adjustment using an inverse probability weights (IPW) method.
“The general risk of herpes zoster is [twofold] higher in patients with rheumatoid arthritis when you compare it with the general population,” said Anja Strangfeld, MD of the German Research Center, Berlin, and one of the three RABBIT [Rheumatoide Arthritis: Biobachtung der Biologika-Therapie] principal investigators.
“If you think of all the treatments that RA patients get, then the risk is further increased with bDMARD and [JAK inhibitor] treatments,” she added in an interview. While the risk was highest with JAK inhibitors, “we also saw that monoclonal TNF antibodies as well as all the other biologic DMARD treatments have a higher risk of herpes zoster in RA patients, compared to csDMARD therapy,” Dr. Strangfeld said.
Adjusted IPW HR for the other RA treatments showed an increased herpes zoster risk for all but the soluble TNF receptor agents, at 1.6 for IL-6 inhibitors (P = .0045) and monoclonal TNFi antibodies (P = .0003), and 1.7 for B-cell targeted therapies (P = .00026) and T-cell costimulation modulators (P = .0048).
Dr. Strangfeld presented these data during the annual European Congress of Rheumatology, held online this year due to COVID-19. The analysis included 12,470 patients with RA enrolled in RABBIT from 2007 onward and who had been treated with monoclonal TNF inhibitor antibodies, cell-targeted therapies, and tsDMARDs such as JAK inhibitors. In all, at the data cutoff at the end of April 2019, 452 cases of herpes zoster were recorded in 433 patients, of which 52 cases were serious.
“The reactivation of the varicella zoster virus causing the herpes zoster is triggered by a decline of cellular immunity. This can be due to aging or immune suppression of any kind,” Dr. Strangfeld said in her presentation.
“The Cox regression [analysis] revealed that higher age and intake of glucocorticoids were associated with an increased risk of herpes zoster,” she reported, with a dose dependent increase with glucocorticoids. IPW HR for age per 10 years was 1.3 (P < .0001) and 1.9 (P = .0022) for higher doses of glucocorticoids (>10 vs. 0 mg/day).
Commenting on the study, rheumatologist and epidemiologist Loreto Carmona, MD, PhD, said: “This is a very interesting study. The results are confident and precise. The frequency of herpes zoster infection [based on crude incidence rate estimates] is very high. However, we must focus on the [multivariable with IPW] analysis after taking into account baseline risk.”
Dr. Carmona, who is the chair of the congress’s Abstract Selection Committee and is the scientific director of the Instituto de Salud Musculoesquelética in Madrid, added: “Having a disease with high levels of activity or a disease refractory to treatments [both of which were very likely used in creating the IPW] levels off the risk a bit. Also, because RA by itself, glucocorticoids, and age all increase the risk. Still, jakinibs [JAK inhibitors] stand out as the treatment related to higher risk of herpes zoster infection.”
Dr. Strangfeld and fellow RABBIT investigators have previously looked at the risk of herpes zoster in patients treated with anti–TNF-alpha agents (JAMA. 2009;301[7]:737-44). They found that monoclonal anti–TNF-alpha agents may be associated with increased risk of herpes zoster, which is now confirmed by the current analysis. The reason for looking at herpes zoster risk again is that since that first analysis, many more therapies have become available for RA during the past 10 years, notably the tsDMARDs.
Herpes zoster may not always be a serious event, Dr. Strangfeld said in the interview, “but it diminishes your quality of life; it can also be associated with pain and may be followed by postherpetic neuralgia, which is very painful.” With new herpes zoster vaccinations available, it is now possible to vaccinate patients more easily. “This is advisable for all kinds of treatments,” she said.
“What we found was quite in agreement with the data that we know from the U.S., from the observational studies, for example from the Corrona database,” Dr. Strangfeld stated. The key finding is that the risk of herpes zoster is increased to some level, almost regardless of which drug is chosen, she said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients with RA,” she suggested.
The German biologics registry RABBIT is supported by a joint unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, Merck Sharp & Dohme, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Dr. Strangfeld has received speaker fees from AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Sanofi-Aventis, and UCB. Dr. Carmona had no relevant conflicts of interest to disclose.
SOURCE: Strangfeld A et al. Ann Rheum Dis. 2020;79[suppl 1]:150. Abstract OP0238.
FROM EULAR 2020 E-CONGRESS
Today’s Top News Highlights: Doctors protest racism, controversial studies retracted
Here are the stories our MDedge editors across specialties think you need to know about today:
#WhiteCoats4BlackLives stands up to racism
Participants in the growing #WhiteCoats4BlackLives protest against racism say it is a chance to use their status as trusted messengers, show themselves as allies of people of color, and demonstrate that they are familiar with how racism has contributed to health disparities.
The medical student-run group WhiteCoats4BlackLives has helped organize ongoing, large-scale events at hospitals, medical campuses, and city centers nationwide.“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in late last month in a city park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Read more.
A conversation on race
In this special episode of the Psychcast podast, host Lorenzo Norris, MD, and fourth-year psychiatry resident Brandon C. Newsome, MD, discuss race relations as physicians in the wake of the death of George Floyd. The pair discuss what their patients are experiencing and what they’re experiencing as black physicians.
“Racism – whether or not you witness it, whether or not you utilize it, whether or not you are the subject of it – affects and hurts us all,” Dr. Norris says. “We all have to start to own that. You can’t just stay siloed, because it is going to affect you.” Listen here.
Two journals retract studies on HCQ
The Lancet has retracted a highly cited study that suggested hydroxychloroquine (HCQ) may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
Three authors of the Lancet article wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO. The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote, leading them to request a retraction of the paper.
In a similar note, the authors requested that the New England Journal of Medicine retract the earlier article as well.
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
Read more.
FDA approves antibiotic to treat pneumonia
The Food and Drug Administration has approved Recarbrio (imipenem-cilastatin and relebactam) for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, of the agency’s Center for Drug Evaluation and Research.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
#WhiteCoats4BlackLives stands up to racism
Participants in the growing #WhiteCoats4BlackLives protest against racism say it is a chance to use their status as trusted messengers, show themselves as allies of people of color, and demonstrate that they are familiar with how racism has contributed to health disparities.
The medical student-run group WhiteCoats4BlackLives has helped organize ongoing, large-scale events at hospitals, medical campuses, and city centers nationwide.“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in late last month in a city park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Read more.
A conversation on race
In this special episode of the Psychcast podast, host Lorenzo Norris, MD, and fourth-year psychiatry resident Brandon C. Newsome, MD, discuss race relations as physicians in the wake of the death of George Floyd. The pair discuss what their patients are experiencing and what they’re experiencing as black physicians.
“Racism – whether or not you witness it, whether or not you utilize it, whether or not you are the subject of it – affects and hurts us all,” Dr. Norris says. “We all have to start to own that. You can’t just stay siloed, because it is going to affect you.” Listen here.
Two journals retract studies on HCQ
The Lancet has retracted a highly cited study that suggested hydroxychloroquine (HCQ) may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
Three authors of the Lancet article wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO. The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote, leading them to request a retraction of the paper.
In a similar note, the authors requested that the New England Journal of Medicine retract the earlier article as well.
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
Read more.
FDA approves antibiotic to treat pneumonia
The Food and Drug Administration has approved Recarbrio (imipenem-cilastatin and relebactam) for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, of the agency’s Center for Drug Evaluation and Research.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
#WhiteCoats4BlackLives stands up to racism
Participants in the growing #WhiteCoats4BlackLives protest against racism say it is a chance to use their status as trusted messengers, show themselves as allies of people of color, and demonstrate that they are familiar with how racism has contributed to health disparities.
The medical student-run group WhiteCoats4BlackLives has helped organize ongoing, large-scale events at hospitals, medical campuses, and city centers nationwide.“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in late last month in a city park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Read more.
A conversation on race
In this special episode of the Psychcast podast, host Lorenzo Norris, MD, and fourth-year psychiatry resident Brandon C. Newsome, MD, discuss race relations as physicians in the wake of the death of George Floyd. The pair discuss what their patients are experiencing and what they’re experiencing as black physicians.
“Racism – whether or not you witness it, whether or not you utilize it, whether or not you are the subject of it – affects and hurts us all,” Dr. Norris says. “We all have to start to own that. You can’t just stay siloed, because it is going to affect you.” Listen here.
Two journals retract studies on HCQ
The Lancet has retracted a highly cited study that suggested hydroxychloroquine (HCQ) may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
Three authors of the Lancet article wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO. The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote, leading them to request a retraction of the paper.
In a similar note, the authors requested that the New England Journal of Medicine retract the earlier article as well.
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
Read more.
FDA approves antibiotic to treat pneumonia
The Food and Drug Administration has approved Recarbrio (imipenem-cilastatin and relebactam) for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia in people aged 18 years and older.
Approval for Recarbrio was based on results of a randomized, controlled clinical trial of 535 hospitalized adults with hospital-acquired and ventilator-associated bacterial pneumonia who received either Recarbrio or piperacillin-tazobactam. After 28 days, 16% of patients who received Recarbrio and 21% of patients who received piperacillin-tazobactam had died.
“As a public health agency, the FDA addresses the threat of antimicrobial-resistant infections by facilitating the development of safe and effective new treatments. These efforts provide more options to fight serious bacterial infections and get new, safe and effective therapies to patients as soon as possible,” said Sumathi Nambiar, MD, MPH, of the agency’s Center for Drug Evaluation and Research.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
#WhiteCoats4BlackLives: A ‘platform for good’
like those on vivid display during the COVID-19 pandemic.
Sporadic protests – with participants in scrubs or white coats kneeling for 8 minutes and 46 seconds in memory of George Floyd – have quickly grown into organized, ongoing, large-scale events at hospitals, medical campuses, and city centers in New York, Indianapolis, Atlanta, Austin, Houston, Boston, Miami, Portland, Sacramento, Los Angeles, Philadelphia, and Albuquerque, among others.
The group WhiteCoats4BlackLives began with a “die-in” protest in 2014, and the medical student–run organization continues to organize, with a large number of protests scheduled to occur simultaneously on June 5 at 1:00 p.m. Eastern Time.
“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in on May 31 in the city’s Washington Square Park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Crystal Nnenne Azu, MD, a third-year internal medicine resident at Indiana University, who has long worked on increasing diversity in medicine, said she helped organize a march and kneel-in at the school’s Eskenazi Hospital campus on June 3 to educate and show support.
Some 500-1,000 health care providers in scrubs and white coats turned out, tweeted one observer.
“Racism is a public health crisis,” Dr. Azu said. “This COVID epidemic has definitely raised that awareness even more for many of our colleagues.”
Disproportionate death rates in blacks and Latinos are “not just related to individual choices but also systemic racism,” she said.
The march also called out police brutality and the “angst” that many people feel about it, said Dr. Azu. “People want an avenue to express their discomfort, to raise awareness, and also show their solidarity and support for peaceful protests,” she said.
A June 4 protest and “die-in” – held to honor black and indigenous lives at the University of New Mexico Health Sciences campus in Albuquerque – was personal for Jaron Kee, MD, a first-year family medicine resident. He was raised on the Navajo reservation in Crystal, New Mexico, and has watched COVID-19 devastate the tribe, adding insult to years of health disparities, police brutality, and neglect of thousands of missing and murdered indigenous women, he said.
Participating is a means of reassuring the community that “we’re allies and that their suffering and their livelihood is something that we don’t underrecognize,” Dr. Kee said. These values spurred him to enter medicine, he said.
Eileen Barrett, MD, MPH, a hospitalist and assistant professor of internal medicine at the University of New Mexico School of Medicine, who also attended the “die-in,” said she hopes that peers, in particular people of color, see that they have allies at work “who are committed to being anti-racist.”
It’s also “a statement to the community at large that physicians and other healthcare workers strive to be anti-racist and do our best to support our African American and indigenous peers, students, patients, and community members,” she said.
Now is different
Some residents said they felt particularly moved to act now – as the country entered a second week of protests in response to George Floyd’s death and as the COVID-19 pandemic highlighted the devastating toll of health disparities.
“This protest feels different to me,” said Ian Fields, MD, a urogynecology fellow at Oregon Health Sciences University (OHSU) School of Medicine. “The events over the last couple of weeks were just a big catalyst for this to explode,” he said.
“I was very intent, as a white male physician, just coming to acknowledge the privilege that I have, and to do something,” Dr. Fields said, adding that as an obstetrician-gynecologist, he sees the results of health disparities daily. He took part in a kneel-in and demonstration with OHSU colleagues on June 2 at Portland’s Pioneer Courthouse Square.
It’s okay to be sad and mourn, Dr. Fields said, but, he added, “nobody needs our tears necessarily right now. They need us to show up and to speak up about what we see going on.”
“It feels like it’s a national conversation,” said Dr. Verghese. The White Coats movement is “not an issue that’s confined to the black community – this is not an issue that’s a ‘black thing’ – this is a humanitarian thing,” she said.
Dr. Verghese, an Indian American who said that no one would mistake her for being white, said she still wants to acknowledge that she has privilege, as well as biases. All the patients in the COVID-19 unit where she works are African American, but she said she hadn’t initially noticed.
“What’s shocking is that I didn’t think about it,” she said. “I do have to recognize my own biases.”
Protesting During a Pandemic
Despite the demands of treating COVID-19 patients, healthcare professionals have made the White Coat protests a priority, they said. Most – but not all – of the White Coats protests have been on medical campuses, allowing health care professionals to quickly assemble and get back to work. Plus, all of the protests have called on attendees to march and gather safely – with masks and distancing.
“Seeing that we are working in the hospital, it’s important for us to be wearing our masks, to be social distancing,” Dr. Azu said. Organizers asked attendees to ensure that they protested in a way that kept them “from worsening the COVID epidemic,” said Dr. Azu.
Unlike many others, the first protest in Portland was in conjunction with a larger group that assembles every evening in the square, said Dr. Fields. The physician protesters were wearing masks and maintaining distance from each other, especially when they kneeled, he said.
The protests have provided an escape from the futility of not being able to do anything for COVID-19 patients except to provide support, said Dr. Verghese. “In so many ways, we find ourselves powerless,” she said.
Protesting, Dr. Verghese added, was “one tiny moment where I got to regain my sense of agency, that I could actually do something about this.”
This article first appeared on Medscape.com.
like those on vivid display during the COVID-19 pandemic.
Sporadic protests – with participants in scrubs or white coats kneeling for 8 minutes and 46 seconds in memory of George Floyd – have quickly grown into organized, ongoing, large-scale events at hospitals, medical campuses, and city centers in New York, Indianapolis, Atlanta, Austin, Houston, Boston, Miami, Portland, Sacramento, Los Angeles, Philadelphia, and Albuquerque, among others.
The group WhiteCoats4BlackLives began with a “die-in” protest in 2014, and the medical student–run organization continues to organize, with a large number of protests scheduled to occur simultaneously on June 5 at 1:00 p.m. Eastern Time.
“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in on May 31 in the city’s Washington Square Park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Crystal Nnenne Azu, MD, a third-year internal medicine resident at Indiana University, who has long worked on increasing diversity in medicine, said she helped organize a march and kneel-in at the school’s Eskenazi Hospital campus on June 3 to educate and show support.
Some 500-1,000 health care providers in scrubs and white coats turned out, tweeted one observer.
“Racism is a public health crisis,” Dr. Azu said. “This COVID epidemic has definitely raised that awareness even more for many of our colleagues.”
Disproportionate death rates in blacks and Latinos are “not just related to individual choices but also systemic racism,” she said.
The march also called out police brutality and the “angst” that many people feel about it, said Dr. Azu. “People want an avenue to express their discomfort, to raise awareness, and also show their solidarity and support for peaceful protests,” she said.
A June 4 protest and “die-in” – held to honor black and indigenous lives at the University of New Mexico Health Sciences campus in Albuquerque – was personal for Jaron Kee, MD, a first-year family medicine resident. He was raised on the Navajo reservation in Crystal, New Mexico, and has watched COVID-19 devastate the tribe, adding insult to years of health disparities, police brutality, and neglect of thousands of missing and murdered indigenous women, he said.
Participating is a means of reassuring the community that “we’re allies and that their suffering and their livelihood is something that we don’t underrecognize,” Dr. Kee said. These values spurred him to enter medicine, he said.
Eileen Barrett, MD, MPH, a hospitalist and assistant professor of internal medicine at the University of New Mexico School of Medicine, who also attended the “die-in,” said she hopes that peers, in particular people of color, see that they have allies at work “who are committed to being anti-racist.”
It’s also “a statement to the community at large that physicians and other healthcare workers strive to be anti-racist and do our best to support our African American and indigenous peers, students, patients, and community members,” she said.
Now is different
Some residents said they felt particularly moved to act now – as the country entered a second week of protests in response to George Floyd’s death and as the COVID-19 pandemic highlighted the devastating toll of health disparities.
“This protest feels different to me,” said Ian Fields, MD, a urogynecology fellow at Oregon Health Sciences University (OHSU) School of Medicine. “The events over the last couple of weeks were just a big catalyst for this to explode,” he said.
“I was very intent, as a white male physician, just coming to acknowledge the privilege that I have, and to do something,” Dr. Fields said, adding that as an obstetrician-gynecologist, he sees the results of health disparities daily. He took part in a kneel-in and demonstration with OHSU colleagues on June 2 at Portland’s Pioneer Courthouse Square.
It’s okay to be sad and mourn, Dr. Fields said, but, he added, “nobody needs our tears necessarily right now. They need us to show up and to speak up about what we see going on.”
“It feels like it’s a national conversation,” said Dr. Verghese. The White Coats movement is “not an issue that’s confined to the black community – this is not an issue that’s a ‘black thing’ – this is a humanitarian thing,” she said.
Dr. Verghese, an Indian American who said that no one would mistake her for being white, said she still wants to acknowledge that she has privilege, as well as biases. All the patients in the COVID-19 unit where she works are African American, but she said she hadn’t initially noticed.
“What’s shocking is that I didn’t think about it,” she said. “I do have to recognize my own biases.”
Protesting During a Pandemic
Despite the demands of treating COVID-19 patients, healthcare professionals have made the White Coat protests a priority, they said. Most – but not all – of the White Coats protests have been on medical campuses, allowing health care professionals to quickly assemble and get back to work. Plus, all of the protests have called on attendees to march and gather safely – with masks and distancing.
“Seeing that we are working in the hospital, it’s important for us to be wearing our masks, to be social distancing,” Dr. Azu said. Organizers asked attendees to ensure that they protested in a way that kept them “from worsening the COVID epidemic,” said Dr. Azu.
Unlike many others, the first protest in Portland was in conjunction with a larger group that assembles every evening in the square, said Dr. Fields. The physician protesters were wearing masks and maintaining distance from each other, especially when they kneeled, he said.
The protests have provided an escape from the futility of not being able to do anything for COVID-19 patients except to provide support, said Dr. Verghese. “In so many ways, we find ourselves powerless,” she said.
Protesting, Dr. Verghese added, was “one tiny moment where I got to regain my sense of agency, that I could actually do something about this.”
This article first appeared on Medscape.com.
like those on vivid display during the COVID-19 pandemic.
Sporadic protests – with participants in scrubs or white coats kneeling for 8 minutes and 46 seconds in memory of George Floyd – have quickly grown into organized, ongoing, large-scale events at hospitals, medical campuses, and city centers in New York, Indianapolis, Atlanta, Austin, Houston, Boston, Miami, Portland, Sacramento, Los Angeles, Philadelphia, and Albuquerque, among others.
The group WhiteCoats4BlackLives began with a “die-in” protest in 2014, and the medical student–run organization continues to organize, with a large number of protests scheduled to occur simultaneously on June 5 at 1:00 p.m. Eastern Time.
“It’s important to use our platform for good,” said Danielle Verghese, MD, a first-year internal medicine resident at Thomas Jefferson University Hospital in Philadelphia, who helped recruit a small group of students, residents, and pharmacy school students to take part in a kneel-in on May 31 in the city’s Washington Square Park.
“As a doctor, most people in society regard me with a certain amount of respect and may listen if I say something,” Dr. Verghese said.
Crystal Nnenne Azu, MD, a third-year internal medicine resident at Indiana University, who has long worked on increasing diversity in medicine, said she helped organize a march and kneel-in at the school’s Eskenazi Hospital campus on June 3 to educate and show support.
Some 500-1,000 health care providers in scrubs and white coats turned out, tweeted one observer.
“Racism is a public health crisis,” Dr. Azu said. “This COVID epidemic has definitely raised that awareness even more for many of our colleagues.”
Disproportionate death rates in blacks and Latinos are “not just related to individual choices but also systemic racism,” she said.
The march also called out police brutality and the “angst” that many people feel about it, said Dr. Azu. “People want an avenue to express their discomfort, to raise awareness, and also show their solidarity and support for peaceful protests,” she said.
A June 4 protest and “die-in” – held to honor black and indigenous lives at the University of New Mexico Health Sciences campus in Albuquerque – was personal for Jaron Kee, MD, a first-year family medicine resident. He was raised on the Navajo reservation in Crystal, New Mexico, and has watched COVID-19 devastate the tribe, adding insult to years of health disparities, police brutality, and neglect of thousands of missing and murdered indigenous women, he said.
Participating is a means of reassuring the community that “we’re allies and that their suffering and their livelihood is something that we don’t underrecognize,” Dr. Kee said. These values spurred him to enter medicine, he said.
Eileen Barrett, MD, MPH, a hospitalist and assistant professor of internal medicine at the University of New Mexico School of Medicine, who also attended the “die-in,” said she hopes that peers, in particular people of color, see that they have allies at work “who are committed to being anti-racist.”
It’s also “a statement to the community at large that physicians and other healthcare workers strive to be anti-racist and do our best to support our African American and indigenous peers, students, patients, and community members,” she said.
Now is different
Some residents said they felt particularly moved to act now – as the country entered a second week of protests in response to George Floyd’s death and as the COVID-19 pandemic highlighted the devastating toll of health disparities.
“This protest feels different to me,” said Ian Fields, MD, a urogynecology fellow at Oregon Health Sciences University (OHSU) School of Medicine. “The events over the last couple of weeks were just a big catalyst for this to explode,” he said.
“I was very intent, as a white male physician, just coming to acknowledge the privilege that I have, and to do something,” Dr. Fields said, adding that as an obstetrician-gynecologist, he sees the results of health disparities daily. He took part in a kneel-in and demonstration with OHSU colleagues on June 2 at Portland’s Pioneer Courthouse Square.
It’s okay to be sad and mourn, Dr. Fields said, but, he added, “nobody needs our tears necessarily right now. They need us to show up and to speak up about what we see going on.”
“It feels like it’s a national conversation,” said Dr. Verghese. The White Coats movement is “not an issue that’s confined to the black community – this is not an issue that’s a ‘black thing’ – this is a humanitarian thing,” she said.
Dr. Verghese, an Indian American who said that no one would mistake her for being white, said she still wants to acknowledge that she has privilege, as well as biases. All the patients in the COVID-19 unit where she works are African American, but she said she hadn’t initially noticed.
“What’s shocking is that I didn’t think about it,” she said. “I do have to recognize my own biases.”
Protesting During a Pandemic
Despite the demands of treating COVID-19 patients, healthcare professionals have made the White Coat protests a priority, they said. Most – but not all – of the White Coats protests have been on medical campuses, allowing health care professionals to quickly assemble and get back to work. Plus, all of the protests have called on attendees to march and gather safely – with masks and distancing.
“Seeing that we are working in the hospital, it’s important for us to be wearing our masks, to be social distancing,” Dr. Azu said. Organizers asked attendees to ensure that they protested in a way that kept them “from worsening the COVID epidemic,” said Dr. Azu.
Unlike many others, the first protest in Portland was in conjunction with a larger group that assembles every evening in the square, said Dr. Fields. The physician protesters were wearing masks and maintaining distance from each other, especially when they kneeled, he said.
The protests have provided an escape from the futility of not being able to do anything for COVID-19 patients except to provide support, said Dr. Verghese. “In so many ways, we find ourselves powerless,” she said.
Protesting, Dr. Verghese added, was “one tiny moment where I got to regain my sense of agency, that I could actually do something about this.”
This article first appeared on Medscape.com.
COVID-19-related inflammatory condition more common in black children in small study
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
More evidence has linked the Kawasaki-like multisystem inflammatory syndrome in children to COVID-19 and suggests that black children have a greater risk of the condition, according to a study published in the BMJ.
A small observational study in Paris found more than half of the 21 children who were admitted for the condition at the city’s pediatric hospital for COVID-19 patients were of African ancestry.
“The observation of a higher proportion of patients of African ancestry is consistent with recent findings, suggesting an effect of either social and living conditions or genetic susceptibility,” wrote Julie Toubiana, MD, PhD, of the University of Paris and the Pasteur Institute, and colleagues.
The findings did not surprise Edward M. Behrens, MD, chief of the division of rheumatology at Children’s Hospital of Philadelphia, whose institution has seen similar disparities that he attributes to social disadvantages.
“Infection rate will be higher in vulnerable populations that are less able to socially distance, have disproportionate numbers of essential workers, and have less access to health care and other resources,” Dr. Behrens said in an interview. “While there may be a role for genetics, environment – including social disparities – is almost certainly playing a role.”
Although the study’s small size is a limitation, he said, “the features described seem to mirror the experience of our center and what has been discussed more broadly amongst U.S. physicians.”
Byron Whyte, MD, a pediatrician in private practice in southeast Washington, found the differences in race interesting, but said the study was too small to draw any conclusions or generalize to the United States. But social disparities related to race are likely similar in France as they are in the United States, he said.
The prospective observational study assessed the clinical and demographic characteristics of all patients under age 18 who met the criteria for Kawasaki disease and were admitted between April 27 and May 20 to the Necker Hospital for Sick Children in Paris.
The 21 children had an average age of 8 years (ranging from 3 to 16), and 57% had at least one parent from sub-Saharan Africa or a Caribbean island; 14% had parents from Asia (two from China and one from Sri Lanka). The authors noted in their discussion that past U.S. and U.K. studies of Kawasaki disease have found a 2.5 times greater risk in Asian-American children and 1.5 times greater risk in African-American children compared with children with European ancestry.
Most of the patients (81%) needed intensive care, with 57% presenting with Kawasaki disease shock syndrome and 67% with myocarditis. Dr. Toubiana and associates also noted that “gastrointestinal symptoms were also unusually common, affecting all of our 21 patients.”
Only nine of the children reported having symptoms of a viral-like illness when they were admitted, primarily headache, cough, coryza, and fever, plus anosmia in one child. Among those children, the Kawasaki symptoms began a median 45 days after onset of the viral symptoms (range 18-79 days).
Only two children showed no positive test result for current COVID-19 infection or antibodies. Eight (38%) of the children had positive PCR tests for SARS-CoV2, and 19 (90%) had positive tests for IgG antibodies. The two patients with both negative tests did not require intensive care and did not have myocarditis.
About half the patients (52%) met all the criteria of Kawasaki disease, and the other 10 had “incomplete Kawasaki disease.” The most common Kawasaki symptoms were the polymorphous skin rash, occurring in 76% of the patients, changes to the lips and oral cavity (76%), and bilateral bulbar conjunctival injection (81%). Three patients (14%) had pleural effusion, and 10 of them (48%) had pericardial effusion, Dr. Toubiana and associates reported.
But Dr. Behrens said he disagrees with the assertion that the illness described in the paper and what he is seeing at Children’s Hospital of Philadelphia is related to Kawasaki disease.
“Most experts here in the U.S. seem to agree this is not Kawasaki disease, but a distinct clinical syndrome called multisystem inflammatory syndrome in children, or MIS-C, that seems to have some overlap with the most nonspecific features of Kawasaki disease,” said Dr. Behrens, who is the Joseph Lee Hollander Chair in Pediatric Rheumatology at Children’s Hospital of Philadelphia. He has coauthored a study currently under review and available as a preprint soon that examines the biologic mechanisms underlying MIS-C.
Neither Dr. Behrens nor Dr. Whyte believed the findings had clinical implications that might change practice, but Dr. Whyte said he will be paying closer attention to the black children he treats – 99% of his practice – who are recovering from COVID-19.
“And, because we know that the concerns of African Americans are often overlooked in health care,” Dr. Whyte said, physicians should “pay a little more attention to symptom reporting on those kids, since there is a possibility that those kids would need hospitalization.”
All the patients in the study were treated with intravenous immunoglobulin, and corticosteroids were administered to 10 of them (48%). Their median hospital stay was 8 days (5 days in intensive care), and all were discharged without any deaths.
“Only one patient had symptoms suggestive of acute covid-19 and most had positive serum test results for IgG antibodies, suggesting that the development of Kawasaki disease in these patients is more likely to be the result of a postviral immunological reaction,” Dr. Toubiana and associates said.
The research received no external funding, and neither the authors nor other quoted physicians had any relevant financial disclosures.
SOURCE: Toubiana J et al. BMJ. 2020 Jun 3, doi: 10.1136 bmj.m2094.
FROM BMJ
COVID-19 neurologic effects: Does the virus directly attack the brain?
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
A new review article summarizes what is known so far, and what clinicians need to look out for.
“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.
The review was published online May 29 in JAMA Neurology.
Brain changes linked to loss of smell
In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.
“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
Can coronaviruses enter the CNS?
Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”
“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.
In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.
“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
Complications of other systemic effects?
Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.
“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.
Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”
Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”
On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”
There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”
Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.
“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
Much is still unknown
“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.
Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”
It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.
Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.
This article first appeared on Medscape.com.
Some biologics may be better than others for averting anterior uveitis
Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.
Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”
The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).
Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.
There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.
After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.
“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”
Findings in context
“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”
Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”
“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”
“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
Study details
Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).
When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.
With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).
When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.
With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).
A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.
Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.
SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.
Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.
Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”
The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).
Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.
There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.
After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.
“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”
Findings in context
“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”
Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”
“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”
“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
Study details
Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).
When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.
With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).
When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.
With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).
A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.
Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.
SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.
Among patients with ankylosing spondylitis or undifferentiated spondyloarthritis, risk for anterior uveitis may hinge on the choice of biologic disease-modifying antirheumatic drug (bDMARD), a large Swedish cohort study suggests.
Study results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year due to COVID-19.
“Randomized, controlled trials indicate that compared to tumor necrosis factor (TNF) inhibitors, secukinumab has similar efficacy regarding axial inflammation in spondyloarthritis and better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease,” noted lead investigator Ulf Lindström, MD, PhD, of the department of rheumatology and inflammation research in the Institute of Medicine at the University of Gothenburg (Sweden). “However, the efficacy of secukinumab, compared to TNF inhibitors, in anterior uveitis has not been extensively studied.”
The investigators used national registry data to study 3,568 patients with ankylosing spondylitis or undifferentiated spondyloarthritis who started bDMARDs in 2005-2018. They considered four agents: the anti–interleukin-17A antibody secukinumab (Cosentyx) and the TNF inhibitors etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade).
Analyses based on 4,523 treatment episodes showed that after excluding the 23% of patients who had previously experienced anterior uveitis, merely 0.9% of patients experienced new-onset anterior uveitis while on their bDMARD, Dr. Lindström reported.
There was confounding by indication, whereby patients with previous anterior uveitis were channeled toward adalimumab and infliximab, and away from secukinumab and etanercept. In addition, there was confounding by line of treatment, with secukinumab usually used in the third line.
After excluding patients who had experienced anterior uveitis in the past year to partly address confounding, the adjusted risk for first on-treatment anterior uveitis was about twice as high with secukinumab and with etanercept as compared with adalimumab. After additionally excluding all biologic treatment episodes beyond the third line, elevation of risk remained significant only for etanercept.
“There is probably a higher occurrence of anterior uveitis on treatment with secukinumab, compared to adalimumab, but there may still be residual confounding and bias that we need to consider,” Dr. Lindström concluded. “As seen previously, there is a higher occurrence of anterior uveitis on etanercept compared to adalimumab or infliximab.”
Findings in context
“These results are not surprising as we have known that secukinumab and etanercept are not good for controlling recurrent and chronic uveitis,” Nigil Haroon MD, PhD, DM, commented in an interview. However, “a single episode of uveitis or infrequent episodes are not usually considered a contraindication to starting these drugs.”
Study caveats included lack of adjustment for uveitis severity and potentially missed uveitis episodes in patients who treated it themselves with steroid eyedrops, he said. “Standard practice is to keep drops with them to start at the earliest possible time point.”
“It would be useful to know the number of patients who stopped medications as a result of uveitis,” added Dr. Haroon, who is codirector of the spondylitis program at the University Health Network and associate professor of medicine and rheumatology at the University of Toronto. “Time-to-event analysis may also be interesting.”
“The study raises an important point regarding channeling bias, and this is important to consider when interpreting clinical trial data as well. Investigators are unlikely to include patients with history of uveitis (or strong family history of inflammatory bowel disease or personal history of gut symptoms) in studies with IL-17 inhibitors and etanercept. Hence, the results have to be interpreted with caution.”
Study details
Dr. Lindström and coinvestigators assessed incidences of any anterior uveitis (ascertained from outpatient ophthalmology visits having this diagnostic code) and of anterior uveitis flares (the subset occurring after a gap of at least 90 days without the diagnosis).
When they excluded patients who had experienced anterior uveitis in the year before starting therapy, secukinumab and etanercept carried the highest incidences of anterior uveitis (6.8 and 7.5 per 100 patient-years, respectively) and anterior uveitis flares (2.8 per 100 patient-years for each), he reported.
With adalimumab as the comparator, adjusted risk for first on-treatment anterior uveitis in this population was significantly higher with secukinumab (hazard ratio, 2.23) and etanercept (hazard ratio, 1.80).
When the investigators additionally excluded episodes of therapy beyond the third line, only etanercept carried notably higher incidences of anterior uveitis (7.0 per 100 patient-years) and anterior uveitis flares (2.6 per 100 patient-years). “This could imply that some of the higher incidence rate seen for secukinumab could be due to the fact that these patients are harder to treat and have received more biologics before,” Dr. Lindström proposed.
With adalimumab again as the comparator, the adjusted risk for first on-treatment anterior uveitis in this population was significantly higher only with etanercept (hazard ratio, 1.85).
A final analysis included all patients who started adalimumab in 2004-2018 and then switched to one of the other agents, dramatically reducing confounding by indication. In this population, the incidence rate ratio of anterior uveitis flares was 3.05 for secukinumab, 1.79 for etanercept, and 0.53 for infliximab, compared with adalimumab.
Dr. Lindström disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding. Dr. Haroon disclosed consulting for Amgen, Abbvie, Eli Lilly, Janssen, Novartis, and UCB.
SOURCE: Lindström U et al. Ann Rheum Dis. 2020;79[suppl 1]:9, Abstract OP0014.
FROM EULAR 2020 E-CONGRESS
COVID-19: Use these strategies to help parents with and without special needs children
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Most people can cope, to some degree, with the multiple weeks of social distancing and stressors related to the pandemic. But what if those stressors became a way of life for a year – or longer? What sorts of skills would be essential not only to survive but to have a renewed sense of resilience?
I know of one group that has had experiences that mirror the challenges faced by the parents of children: the parents of special needs children. As I argued previously, those parents have faced many of the challenges presented by COVID-19. Among those challenges are social distancing and difficulty accessing everyday common experiences. These parents know that they have to manage more areas of their children’s rearing than do their counterparts.
In addition to having to plan for how to deal with acute urgent or emergent medical situations involving their special needs children, these parents also must prepare for the long-term effects of managing children who require ongoing daily care, attention, and dedication.
These strategies can help the parents of special needs kids find a sense of mastery and comfort. The hope is that, after practicing them for long periods of time, the strategies become second nature.
Here are several strategies that might help patients with children during this pandemic:
- Take time to reset: Sometimes it is helpful for parents to take a minute away from a difficult impasse with their kids to reset and take their own “time out.” A few seconds of mental time away from the “scene” provides space and a mental reminder that the minute that just happened is finite, and that a whole new one is coming up next. The break provides a sense of hope. This cognitive reframing could be practiced often.
- Re-enter the challenging scene with a warm voice: Parents model for their children, but they also are telling their own brains that they, too, can calm down. This approach also de-escalates the situation and allows children to get used to hearing directions from someone who is in control – without hostility or irritability.
- Keep a sense of humor; it might come in handy: This is especially the case when tension is in the home, or when facing a set of challenging bad news. As an example, consider how some situations are so repetitive that they border on the ridiculous – such as a grown child having a tantrum at a store. Encourage the children to give themselves permission to cry first so they can laugh second, and then move on.
- Establish a routine for children that is self-reinforcing, and allows for together and separate times: They can, as an example: A) Get ready for the day all by themselves, or as much as they can do independently, before they come down and then B) have breakfast. Then, the child can C) do homework, and then D) go play outside. The routine would then continue on its own without outside reinforcers.
- Tell the children that they can get to the reinforcing activity only after completing the previous one. Over time, they learn to take pride in completing the first activity and doing so more independently. Not having to wait to be told what to do all the time fosters a sense of independence.
- Plan for meals and fun tasks together, and separate for individual work. This creates a sense of change and gives the day a certain flow. Establish routines that are predictable for the children that can be easily documented for the whole family on a calendar. Establish a beginning and an end time to the work day. Mark the end of the day with a chalk line establishing when the family can engage in a certain activity, for example, going for a family bike ride. Let the routine honor healthy circadian rhythms for sleep/wakeful times, and be consistent.
- Feed the brain and body the “good stuff”: Limit negative news, and surround the children with people who bring them joy or provide hope. Listen to inspirational messages and uplifting music. Give the children food that nourishes and energizes their bodies. Take in the view outside, the greenery, or the sky if there is no green around. Connect with family/friends who are far away.
- Make time to replenish with something that is meaningful/productive/helpful: Parents have very little time for themselves when they are “on,” so when they can actually take a little time to recharge, the activity should check many boxes. For example, encourage them to go for a walk (exercise) while listening to music (relax), make a phone call to someone who can relate to their situation (socialize), pray with someone (be spiritual), or sit in their rooms to get some alone quiet time (meditate). Reach out to those who are lonely. Network. Mentor. Volunteer.
- Develop an eye for noticing the positive: Instead of hoping for things to go back to the way they were, tell your patients to practice embracing without judgment the new norm. Get them to notice the time they spend with their families. Break all tasks into many smaller tasks, so there is more possibility of observing progress, and it is evident for everyone to see. Learn to notice the small changes that they want to see in their children. Celebrate all that can be celebrated by stating the obvious: “You wiped your face after eating. You are observant; you are noticing when you have something on your face.”
- State when a child is forgiving, helpful, or puts forward some effort. Label the growth witnessed. The child will learn that that is who they are over time (“observant”). Verbalizing these behaviors also will provide patients with a sense of mastery over parenting, because they are driving the emotional and behavioral development of their children in a way that also complements their family values.
- Make everyone in the family a contributor and foster a sense of gratitude: Give everyone a reason to claim that their collaboration and effort are a big part of the plan’s success. Take turns to lessen everyone’s burden and to thank them for their contributions. Older children can take on leadership roles, even in small ways. Younger children can practice being good listeners, following directions, and helping. Reverse the roles when possible.
Special needs families sometimes have to work harder than others to overcome obstacles, grow, and learn to support one another. Since the pandemic, many parents have been just as challenged. Mastering the above skills might provide a sense of fulfillment and agency, as well as an appreciation for the unexpected gifts that special children – and all children – have to offer.
Dr. Sotir is a psychiatrist with a private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. She has no disclosures.
Tramadol mortality risk in osteoarthritis could outweigh benefits
Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.
Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).
Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.
However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.
This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).
Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.
Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).
“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.
Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).
“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).
“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”
According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”
Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.
Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.
With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).
“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”
He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”
Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.
“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”
The study authors had no conflicts of interest.
SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.
Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.
Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).
Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.
However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.
This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).
Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.
Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).
“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.
Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).
“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).
“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”
According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”
Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.
Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.
With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).
“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”
He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”
Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.
“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”
The study authors had no conflicts of interest.
SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.
Patients with OA treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs, according to the results of a large, population-based study performed in British Columbia.
Within 1 year of starting treatment, 296 of 13,798 patients treated with tramadol had died, compared with 246 of 13,798 treated with naproxen, giving a death rate of 21.5 versus 17.8 per 1,000 person-years, and representing a 20% increase in all-cause mortality versus the NSAID (hazard ratio, 1.2).
Similar results were seen comparing tramadol with diclofenac and tramadol with cyclooxygenase (COX)-2 inhibitors, but with increasing death rates of 24.8 versus 19.5 per 1,000 person-years (HR, 1.3) and 23.6 versus 15.7 per 1,000 person-years (HR, 1.5), respectively.
However, all-cause mortality was lower with tramadol than with the opiate painkiller, codeine (21.5 vs. 25.5 per 1,000 person-years; HR, 0.8), reported Ms. Lingyi Li, a PhD student from the University of British Columbia, Vancouver, at the annual European Congress of Rheumatology, held online this year due to COVID-19.
This is not the first time that tramadol’s excess mortality risk has been highlighted. Indeed, just last year (JAMA. 2019;321[10]:969-82), researchers using The Health Improvement Network database reported found that tramadol was associated with higher all-cause mortality than two COX-2 inhibitors, celecoxib (31.2 versus 18.4 per 1,000 person-years) and etoricoxib (25.7 versus 12.8 per 1,000 person-years).
Ms. Li and associates’ data not only now add further weight to those findings, but also go a step further by also looking at other serious risks associated with tramadol’s use among patients with OA. “The objective of this study is to compare tramadol with other commonly prescribed pain relief medications on the risk of several severe outcomes, including mortality, cardiovascular diseases [CVD], venous thromboembolism [VTE], and hip fracture,” Ms. Li said during her virtual presentation.
Using sequential propensity score matching, the researchers compared data on patients in British Columbia during 2005-2014 with a first prescription of tramadol (56,325), the NSAIDs naproxen (n = 13,798) or diclofenac (n = 17,675), COX-2 inhibitors (17,039), or codeine (n = 7,813).
“For CVD, we found that there is a higher risk among tramadol users, compared with diclofenac [HR, 1.2] and COX-2 inhibitors [HR, 1.2], but not with naproxen [HR, 1.0] and codeine [HR, 0.9] users,” Ms. Li reported.
Similarly, the 1-year risk of VTE was significantly higher among tramadol users only when compared with diclofenac (HR, 1.5) and COX-2 inhibitors (HR, 1.7).
“For hip fractures, tramadol initiation was associated with an increased risk of hip fractures, compared with all NSAIDs, but not with codeine,” Ms. Li said. The risk of hip fractures was 40%-50% higher with tramadol versus naproxen (HR, 1.4), diclofenac and COX-2 inhibitors (both HR, 1.5).
“Our results suggest an unfavorable safety profile of tramadol use,” Ms. Li said, suggesting that “several guidelines on tramadol use in clinical practice might need to be revisited.”
According to a recent Cochrane review there is “moderate-quality evidence” that tramadol “has no important benefit on mean pain or function in people with osteoarthritis.” The authors of the review wrote that, while some patients might glean a benefit from treatment, the evidence suggests that “adverse events probably cause substantially more participants to stop taking tramadol.”
Current guidance on the use of tramadol varies. The American Academy of Orthopaedic Surgeons guidelines recommend its use in patients with symptomatic knee OA on a par with NSAIDs while the American College of Rheumatology guidance (Arthritis Care Res. 2020;72[2]:149-62) conditionally recommends that it be used only if there is no real alternative, such as a contraindication to NSAIDs or pain relief is ineffective.
Patients with rheumatic disease are increasingly taking opioid painkillers such as tramadol, with other data reported at the EULAR 2020 E-Congress showing a rise from 15% in 2007 to 25% in 2016 in the Catalonia region of Spain alone. A rise from 5% to 10% has previously been reported in the United States from 2003 to 2009.
With increasing rates of tramadol prescribing, the worry is that perhaps tramadol is not as safe a people think it is, as Thomas Schwenk, MD, pointed out when he reviewed the previous research showing excess mortality with tramadol (NEJM Journal Watch, March 2019).
“The opioid agonist tramadol often is prescribed for patients with osteoarthritis pain because it is thought to be safer than opioids or nonsteroidal anti-inflammatory drugs,” he observed. Dr. Schwenk, who is dean of the University of Nevada, Reno, added that the “results [of that study] suggest that tramadol is not as safe as some people believe.”
He suggested cautious prescribing: “Tramadol might be an option for patients in whom NSAIDs are contraindicated, but it should be prescribed as judiciously as traditional opioids.”
Responsible prescribing to avoid opioid misuse in patients with rheumatic diseases was also advocated in a EULAR press release from the congress. A study from Iceland was highlighted that found patients with inflammatory arthritis frequently did not stop taking opioids after the source of their pain had gone; in fact, their use went up despite being treated with tumor necrosis factor inhibitors.
“We would like to raise awareness of a responsible approach both by the prescribers and also the patients,” said John Isaacs, PhD, of the University of Newcastle (England). “In order to alleviate chronic pain, medications should in any case only be part of a comprehensive therapy program, in which doctors, psychologists, and physiotherapists work together.”
The study authors had no conflicts of interest.
SOURCE: Li L et al. Ann Rheum Dis. 2020;79[suppl 1]:118, Abstract OP0191.
FROM EULAR 2020 E-CONGRESS
Lancet, NEJM retract studies on hydroxychloroquine for COVID-19
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.
The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.
The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.
Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.
The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.
“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.
Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.
The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”
The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.
“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”
In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”
Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.
A version of this article originally appeared on Medscape.com.