For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

For adult outpatients with moderate to severe Crohn’s disease, new guidelines from the American Gastroenterological Association strongly recommend induction and maintenance therapy with anti–tumor necrosis factor–alpha agents or ustekinumab over no treatment.

“Although [related] evidence supporting infliximab and adalimumab was moderate certainty, the evidence for certolizumab pegol was low certainty,” wrote Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center in Boston and his associates, on behalf of the AGA Clinical Guidelines Committee in Gastroenterology. Vedolizumab received a conditional recommendation based on less robust evidence for induction in this setting.

Outcomes in Crohn’s disease have improved, likely “because of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer,” Dr. Feuerstein and his associates wrote.

This update reflects these changes, strongly recommending biologic monotherapy over thiopurine monotherapy for induction. It also suggests “early induction with a biologic, with or without an immunomodulator, rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.” For the latter assessment, the guidelines noted that some studies were open label (which increases risk of bias) and that upfront combination therapy with a biologic and an immunomodulator could sometimes lead to overtreatment. Nonetheless, studies shown associations between the step-up approach and “a potential risk of harm from disease progression related to inadequate disease therapy.”

The guidelines also recommend that patients who have never received biologic drugs receive induction therapy with infliximab, adalimumab, or ustekinumab, rather than certolizumab pegol. This strong recommendation reflects the findings of a network meta-analysis conducted by the AGA in which certolizumab pegol was least effective, with no evidence for clear differences in efficacy among infliximab, adalimumab, and ustekinumab. A network meta-analysis is a type of study that enables experts to compare therapies indirectly when head-to-head trials are lacking.

For patients who are naive to both biologics and immunomodulators, the guidelines suggest combination treatment with infliximab or adalimumab plus a thiopurine rather than monotherapy with either biologic. Because of a lack of randomized controlled trials, no recommendation is made regarding combination therapy with ustekinumab or vedolizumab.

For patients who have received but never responded to anti-TNF-alpha therapy (so-called primary nonresponders), ustekinumab is strongly recommended, and vedolizumab is conditionally recommended. For patients who initially responded to infliximab and then lost their response (secondary nonresponders), adalimumab and ustekinumab are strongly recommended, while vedolizumab receives another conditional recommendation.

For patients with moderate to severe luminal disease, induction and maintenance with infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab are recommended over no treatment. Thiopurine monotherapy is suggested over no treatment for maintenance of remission, but not for induction. For methotrexate, subcutaneous or intramuscular monotherapy is suggested over no treatment. The sole available trial on oral methotrexate (12.5 mg/week) was negative, and “it is not clear if a higher dose would have been more effective,” according to the guidelines. They strongly recommend against using 5-aminosalicytes or sulfasalazine because of lack of efficacy for maintaining remission and suggest not using natalizumab because of the risk of progressive multifocal leukoencephalopathy (PML). Corticosteroids are considered preferable to no treatment for induction but not for maintenance.

For patients with fistulizing disease, infliximab has “the most robust evidence” and receives a strong recommendation for induction and maintenance, while adalimumab, ustekinumab, and vedolizumab receive conditional recommendations. “In contrast, evidence suggests certolizumab pegol may not be effective for induction of fistula remission,” the guidelines state. For patients with perianal disease with an active fistula but no abscess, combining biologics with antibiotics is strongly recommended over biologic monotherapy.

The guidelines define moderate to severe Crohn’s disease as a Crohn’s Disease Activity Index (CDAI) score of 220 or higher, the typical cutoff used in clinical trials. The recommendations apply to outpatient management, but in most cases would also apply to inpatients.

An expert commentary accompanying the guidelines praises their “rigorous methods” based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Edith Y. Ho, MD, of Stanford (Calif.) University and her associates also laud the “innovative methods” that were used to compare treatments and assess data quality. In addition to the network meta-analysis, the guidelines set an a priori minimal clinically important difference (MCID) score of 10% for risk of treatment failure versus placebo. This led to more clinically relevant guidance, such as the conditional recommendation for vedolizumab in luminal disease since this drug did not meet the MCID threshold. Finally, the commentators emphasized that the guidelines are meant to facilitate, not dictate, treatment decisions: “Choice of therapies and treatment strategies will continue to rely on clinical judgment as well, and will continue to be informed by patient-specific values and preferences.”

The AGA Institute was the sole source of funding. Four coauthors disclosed ties to Celgene, Takeda, Pendopharm, Merck Canada, Guardant Health, Ferring, and AbbVie. Dr. Feurstein and the other guidelines coauthors reported having no conflicts of interest. Some authors on the editorial disclosed relationships with AbbVie, Pfizer, and Janssen, but the remaining had no conflicts to disclose.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.