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Zoster vaccination does not appear to increase flare risk in patients with immune-mediated inflammatory disease
, according to research published in Arthritis & Rheumatology.
The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.
The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.
They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.
Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.
Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.
Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.
“Anytime you are vaccinating a patient with an autoimmune disease, especially one on a biologic, you always worry about the risk of flares,” said Dr. Bose. “Any time you tamper with the immune system, there is a risk of flares.”
The study serves as a clarification for the primary care setting, said Dr. Bose. “A lot of the time, the shingles vaccine is administered not by rheumatology but by primary care or through the pharmacy,” she said. “This study puts them [primary care physicians] at ease.”
Findings from the study reflect that most RZV vaccinations were administered in pharmacies.
One of the weaknesses of the study is that the investigators did not include patients younger than 50 years old, said Dr. Bose. “It would have been nice if they could have looked at younger patients,” she said. “We try to vaccinate all our [immunocompromised] adult patients, even the younger ones, because they are also at risk for shingles.”
Given that there are increasing options of medical therapies in rheumatology that are immunomodulatory, the subject of vaccination for patients is often one of discussion, added Dr. Bose.
Arthur Kavanaugh, MD, professor of medicine, University of California San Diego (UCSD), La Jolla, Calif., and director of the Center for Innovative Therapy in the UCSD Division of Rheumatology, Allergy, and Immunology, told this news organization that a strength of the study is its large numbers of patients but noted the shortcoming of using claims data. “Claims data has inherent limitations, such as the lack of detailed granular data on the patients,” wrote Dr. Kavanaugh, who was not involved with the study. He described this investigation as “really about the first evidence that I am aware of addressing this issue.”
No funding source was listed. One author disclosed having received research grants and consulting fees received from Pfizer and GSK for unrelated work; the other authors had no disclosures. Dr. Bose and Dr. Kavanaugh had no relevant disclosures.
, according to research published in Arthritis & Rheumatology.
The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.
The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.
They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.
Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.
Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.
Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.
“Anytime you are vaccinating a patient with an autoimmune disease, especially one on a biologic, you always worry about the risk of flares,” said Dr. Bose. “Any time you tamper with the immune system, there is a risk of flares.”
The study serves as a clarification for the primary care setting, said Dr. Bose. “A lot of the time, the shingles vaccine is administered not by rheumatology but by primary care or through the pharmacy,” she said. “This study puts them [primary care physicians] at ease.”
Findings from the study reflect that most RZV vaccinations were administered in pharmacies.
One of the weaknesses of the study is that the investigators did not include patients younger than 50 years old, said Dr. Bose. “It would have been nice if they could have looked at younger patients,” she said. “We try to vaccinate all our [immunocompromised] adult patients, even the younger ones, because they are also at risk for shingles.”
Given that there are increasing options of medical therapies in rheumatology that are immunomodulatory, the subject of vaccination for patients is often one of discussion, added Dr. Bose.
Arthur Kavanaugh, MD, professor of medicine, University of California San Diego (UCSD), La Jolla, Calif., and director of the Center for Innovative Therapy in the UCSD Division of Rheumatology, Allergy, and Immunology, told this news organization that a strength of the study is its large numbers of patients but noted the shortcoming of using claims data. “Claims data has inherent limitations, such as the lack of detailed granular data on the patients,” wrote Dr. Kavanaugh, who was not involved with the study. He described this investigation as “really about the first evidence that I am aware of addressing this issue.”
No funding source was listed. One author disclosed having received research grants and consulting fees received from Pfizer and GSK for unrelated work; the other authors had no disclosures. Dr. Bose and Dr. Kavanaugh had no relevant disclosures.
, according to research published in Arthritis & Rheumatology.
The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.
The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.
They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.
Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.
Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.
Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.
“Anytime you are vaccinating a patient with an autoimmune disease, especially one on a biologic, you always worry about the risk of flares,” said Dr. Bose. “Any time you tamper with the immune system, there is a risk of flares.”
The study serves as a clarification for the primary care setting, said Dr. Bose. “A lot of the time, the shingles vaccine is administered not by rheumatology but by primary care or through the pharmacy,” she said. “This study puts them [primary care physicians] at ease.”
Findings from the study reflect that most RZV vaccinations were administered in pharmacies.
One of the weaknesses of the study is that the investigators did not include patients younger than 50 years old, said Dr. Bose. “It would have been nice if they could have looked at younger patients,” she said. “We try to vaccinate all our [immunocompromised] adult patients, even the younger ones, because they are also at risk for shingles.”
Given that there are increasing options of medical therapies in rheumatology that are immunomodulatory, the subject of vaccination for patients is often one of discussion, added Dr. Bose.
Arthur Kavanaugh, MD, professor of medicine, University of California San Diego (UCSD), La Jolla, Calif., and director of the Center for Innovative Therapy in the UCSD Division of Rheumatology, Allergy, and Immunology, told this news organization that a strength of the study is its large numbers of patients but noted the shortcoming of using claims data. “Claims data has inherent limitations, such as the lack of detailed granular data on the patients,” wrote Dr. Kavanaugh, who was not involved with the study. He described this investigation as “really about the first evidence that I am aware of addressing this issue.”
No funding source was listed. One author disclosed having received research grants and consulting fees received from Pfizer and GSK for unrelated work; the other authors had no disclosures. Dr. Bose and Dr. Kavanaugh had no relevant disclosures.
Large study reaffirms rare risk of TNF inhibitor–induced psoriasis in patients with RA, IBD
according to a new study published in JAMA Dermatology.
Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.
They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.
The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.
Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.
The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).
Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
Best evidence to date on risk
Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.
The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.
Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”
For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”
In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”
However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.
The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.
What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.
“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”
He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”
The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.
according to a new study published in JAMA Dermatology.
Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.
They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.
The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.
Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.
The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).
Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
Best evidence to date on risk
Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.
The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.
Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”
For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”
In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”
However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.
The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.
What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.
“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”
He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”
The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.
according to a new study published in JAMA Dermatology.
Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.
They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.
The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.
Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.
The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).
Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
Best evidence to date on risk
Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.
The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.
Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”
For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”
In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”
However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.
The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.
What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.
“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”
He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”
The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.
FROM JAMA DERMATOLOGY
Acute exacerbations common and often fatal in RA-ILD
Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.
The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.
“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.
“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.
The study was published online in Respiratory Medicine.
Patient features
The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.
Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.
Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.
, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.
The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.
“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
Survivors versus nonsurvivors
Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.
Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.
As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.
The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
Cause of death
The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.
“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”
“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.
“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.
“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.
As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.
“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.
Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.
No specific funding source was noted. The authors have no conflicts of interest to declare.
Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.
The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.
“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.
“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.
The study was published online in Respiratory Medicine.
Patient features
The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.
Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.
Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.
, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.
The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.
“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
Survivors versus nonsurvivors
Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.
Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.
As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.
The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
Cause of death
The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.
“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”
“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.
“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.
“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.
As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.
“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.
Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.
No specific funding source was noted. The authors have no conflicts of interest to declare.
Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.
The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.
“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.
“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.
The study was published online in Respiratory Medicine.
Patient features
The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.
Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.
Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.
, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.
The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.
“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
Survivors versus nonsurvivors
Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.
Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.
As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.
The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
Cause of death
The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.
“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”
“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.
“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.
“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.
As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.
“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.
Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.
No specific funding source was noted. The authors have no conflicts of interest to declare.
Commentary: Examining Lower Doses and Effectiveness in RA Treatments, July 2022
In keeping with other studies suggesting that lower-than-standard doses of rituximab (for example, two 500 mg doses every 6 months) are effective in the treatment of rheumatoid arthritis (RA), Bertsias and colleagues evaluated the efficacy of low-dose rituximab (1 g every 6 months) in a cohort of patients with RA. Of 361 patients in the initial registry, 81 achieved sustained low disease activity or remission on standard rituximab regimens and were transitioned to the low-dose regimen; their outcomes were compared with the 280 patients in the registry who received a standard-dose regimen. Only 7.5% experienced flares of RA (compared with 5.9% in the standard-dose group), and patients in the low-dose group had fewer serious adverse events, infections, and hospitalizations. Tapering biologic disease-modifying antirheumatic drugs (DMARD) may thus be a reasonable strategy for some patients with RA, with an eye to their prior results with the medication.
The prospect of achieving sustained DMARD-free remission (SDFR) in people with RA has seemed increasingly feasible in recent studies, although it seems to be affected by anti-citrullinated protein/peptide antibody (ACPA) positivity. That is, people who are ACPA-negative are more likely to reach this target. Verstappen and colleagues examined MRI patterns of joint inflammation in the Leiden Early Arthritis Clinic cohort, as well as another cohort of patients with RA, but only included patients with an RA duration > 1 year to reduce the likelihood of misclassification. Interestingly, ACPA-positive patients who achieved SDFR tended to have lower baseline evidence of joint inflammation (including erosions, synovitis, and osteitis), which was persistent throughout follow-up, whereas ACPA-negative patients who achieved SDFR had similar joint inflammation at baseline to those who did not, but had a better initial response to DMARD therapy. Further study of the potential impact of treatment based on ACPA status would be helpful.
Recent results from the ORAL Surveillance postmarketing safety analysis suggest that tofacitinib is associated with an increased risk for cancer in patients with RA patients who are aged >50 years, compared with anti–tumor necrosis factor (TNF) agents. Khosrow-Khavar and colleagues used insurance claims data to further investigate the risk for cancer with tofacitinib vs anti-TNF agents. They created two cohorts of patients who were new users of anti-TNF agents or tofacitinib: One was a "real-world" cohort including all patients with RA, whereas the other applied the inclusion and exclusion criteria from the ORAL Surveillance trial, including age >50 years, one cardiovascular risk factor, and use of methotrexate. Results from the real-world cohort, including over 10,000 patients who had used tofacitinib, did not show any increase in cancer risk, whereas the trial-simulating conditions did yield higher numbers of cancers in the group exposed to tofacitinib. Though reassuring, these results are limited by the short follow-up duration, and longer-term follow-up studies are necessary for further evaluation.
In another interesting note with respect to medication morbidity and risk, Xu and colleagues performed a meta-analysis looking at the association of methotrexate use and mortality in patients with RA. Only 15 studies were included in the final analysis, though they did encompass a large total number of patients. Overall, methotrexate use in these studies was associated with lower rates of overall mortality as well as mortality due to cardiovascular and interstitial lung disease. However, conclusions as to the direct impact of methotrexate were limited by the heterogeneity of study designs, doses of methotrexate, and additional therapy as well as comparators.
In keeping with other studies suggesting that lower-than-standard doses of rituximab (for example, two 500 mg doses every 6 months) are effective in the treatment of rheumatoid arthritis (RA), Bertsias and colleagues evaluated the efficacy of low-dose rituximab (1 g every 6 months) in a cohort of patients with RA. Of 361 patients in the initial registry, 81 achieved sustained low disease activity or remission on standard rituximab regimens and were transitioned to the low-dose regimen; their outcomes were compared with the 280 patients in the registry who received a standard-dose regimen. Only 7.5% experienced flares of RA (compared with 5.9% in the standard-dose group), and patients in the low-dose group had fewer serious adverse events, infections, and hospitalizations. Tapering biologic disease-modifying antirheumatic drugs (DMARD) may thus be a reasonable strategy for some patients with RA, with an eye to their prior results with the medication.
The prospect of achieving sustained DMARD-free remission (SDFR) in people with RA has seemed increasingly feasible in recent studies, although it seems to be affected by anti-citrullinated protein/peptide antibody (ACPA) positivity. That is, people who are ACPA-negative are more likely to reach this target. Verstappen and colleagues examined MRI patterns of joint inflammation in the Leiden Early Arthritis Clinic cohort, as well as another cohort of patients with RA, but only included patients with an RA duration > 1 year to reduce the likelihood of misclassification. Interestingly, ACPA-positive patients who achieved SDFR tended to have lower baseline evidence of joint inflammation (including erosions, synovitis, and osteitis), which was persistent throughout follow-up, whereas ACPA-negative patients who achieved SDFR had similar joint inflammation at baseline to those who did not, but had a better initial response to DMARD therapy. Further study of the potential impact of treatment based on ACPA status would be helpful.
Recent results from the ORAL Surveillance postmarketing safety analysis suggest that tofacitinib is associated with an increased risk for cancer in patients with RA patients who are aged >50 years, compared with anti–tumor necrosis factor (TNF) agents. Khosrow-Khavar and colleagues used insurance claims data to further investigate the risk for cancer with tofacitinib vs anti-TNF agents. They created two cohorts of patients who were new users of anti-TNF agents or tofacitinib: One was a "real-world" cohort including all patients with RA, whereas the other applied the inclusion and exclusion criteria from the ORAL Surveillance trial, including age >50 years, one cardiovascular risk factor, and use of methotrexate. Results from the real-world cohort, including over 10,000 patients who had used tofacitinib, did not show any increase in cancer risk, whereas the trial-simulating conditions did yield higher numbers of cancers in the group exposed to tofacitinib. Though reassuring, these results are limited by the short follow-up duration, and longer-term follow-up studies are necessary for further evaluation.
In another interesting note with respect to medication morbidity and risk, Xu and colleagues performed a meta-analysis looking at the association of methotrexate use and mortality in patients with RA. Only 15 studies were included in the final analysis, though they did encompass a large total number of patients. Overall, methotrexate use in these studies was associated with lower rates of overall mortality as well as mortality due to cardiovascular and interstitial lung disease. However, conclusions as to the direct impact of methotrexate were limited by the heterogeneity of study designs, doses of methotrexate, and additional therapy as well as comparators.
In keeping with other studies suggesting that lower-than-standard doses of rituximab (for example, two 500 mg doses every 6 months) are effective in the treatment of rheumatoid arthritis (RA), Bertsias and colleagues evaluated the efficacy of low-dose rituximab (1 g every 6 months) in a cohort of patients with RA. Of 361 patients in the initial registry, 81 achieved sustained low disease activity or remission on standard rituximab regimens and were transitioned to the low-dose regimen; their outcomes were compared with the 280 patients in the registry who received a standard-dose regimen. Only 7.5% experienced flares of RA (compared with 5.9% in the standard-dose group), and patients in the low-dose group had fewer serious adverse events, infections, and hospitalizations. Tapering biologic disease-modifying antirheumatic drugs (DMARD) may thus be a reasonable strategy for some patients with RA, with an eye to their prior results with the medication.
The prospect of achieving sustained DMARD-free remission (SDFR) in people with RA has seemed increasingly feasible in recent studies, although it seems to be affected by anti-citrullinated protein/peptide antibody (ACPA) positivity. That is, people who are ACPA-negative are more likely to reach this target. Verstappen and colleagues examined MRI patterns of joint inflammation in the Leiden Early Arthritis Clinic cohort, as well as another cohort of patients with RA, but only included patients with an RA duration > 1 year to reduce the likelihood of misclassification. Interestingly, ACPA-positive patients who achieved SDFR tended to have lower baseline evidence of joint inflammation (including erosions, synovitis, and osteitis), which was persistent throughout follow-up, whereas ACPA-negative patients who achieved SDFR had similar joint inflammation at baseline to those who did not, but had a better initial response to DMARD therapy. Further study of the potential impact of treatment based on ACPA status would be helpful.
Recent results from the ORAL Surveillance postmarketing safety analysis suggest that tofacitinib is associated with an increased risk for cancer in patients with RA patients who are aged >50 years, compared with anti–tumor necrosis factor (TNF) agents. Khosrow-Khavar and colleagues used insurance claims data to further investigate the risk for cancer with tofacitinib vs anti-TNF agents. They created two cohorts of patients who were new users of anti-TNF agents or tofacitinib: One was a "real-world" cohort including all patients with RA, whereas the other applied the inclusion and exclusion criteria from the ORAL Surveillance trial, including age >50 years, one cardiovascular risk factor, and use of methotrexate. Results from the real-world cohort, including over 10,000 patients who had used tofacitinib, did not show any increase in cancer risk, whereas the trial-simulating conditions did yield higher numbers of cancers in the group exposed to tofacitinib. Though reassuring, these results are limited by the short follow-up duration, and longer-term follow-up studies are necessary for further evaluation.
In another interesting note with respect to medication morbidity and risk, Xu and colleagues performed a meta-analysis looking at the association of methotrexate use and mortality in patients with RA. Only 15 studies were included in the final analysis, though they did encompass a large total number of patients. Overall, methotrexate use in these studies was associated with lower rates of overall mortality as well as mortality due to cardiovascular and interstitial lung disease. However, conclusions as to the direct impact of methotrexate were limited by the heterogeneity of study designs, doses of methotrexate, and additional therapy as well as comparators.
Rheumatoid arthritis increases mortality risk in chronic kidney disease
Key clinical point: Patients with both chronic kidney disease (CKD) and rheumatoid arthritis (RA) were at an increased risk for mortality compared with those with CKD alone, with RA having no impact on progressive renal decline.
Major finding: Presence of both CKD and RA vs. CKD alone was associated with an increased risk for all-cause mortality (adjusted hazard ratio [aHR] 1.73; 95% CI 1.27-2.35) and composite of myocardial infarction, cerebrovascular accident, heart failure, or death (aHR 1.65; 95% CI 1.27-2.15), without significantly increasing the risk for progressive renal decline.
Study details: The data come from a retrospective study including 3333 patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study, of which 83 patients had RA and were taking a disease-modifying antirheumatic therapy.
Disclosures: CRIC study was supported by the US National Institute of Diabetes and Digestive and Kidney Diseases. No conflicts of interest were declared.
Source: Ezeanuna MN et al. Association of rheumatoid arthritis with mortality in chronic kidney disease: a cohort study. Clin Rheumatol. 2022 (May 25). Doi: 10.1007/s10067-022-06223-x
Key clinical point: Patients with both chronic kidney disease (CKD) and rheumatoid arthritis (RA) were at an increased risk for mortality compared with those with CKD alone, with RA having no impact on progressive renal decline.
Major finding: Presence of both CKD and RA vs. CKD alone was associated with an increased risk for all-cause mortality (adjusted hazard ratio [aHR] 1.73; 95% CI 1.27-2.35) and composite of myocardial infarction, cerebrovascular accident, heart failure, or death (aHR 1.65; 95% CI 1.27-2.15), without significantly increasing the risk for progressive renal decline.
Study details: The data come from a retrospective study including 3333 patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study, of which 83 patients had RA and were taking a disease-modifying antirheumatic therapy.
Disclosures: CRIC study was supported by the US National Institute of Diabetes and Digestive and Kidney Diseases. No conflicts of interest were declared.
Source: Ezeanuna MN et al. Association of rheumatoid arthritis with mortality in chronic kidney disease: a cohort study. Clin Rheumatol. 2022 (May 25). Doi: 10.1007/s10067-022-06223-x
Key clinical point: Patients with both chronic kidney disease (CKD) and rheumatoid arthritis (RA) were at an increased risk for mortality compared with those with CKD alone, with RA having no impact on progressive renal decline.
Major finding: Presence of both CKD and RA vs. CKD alone was associated with an increased risk for all-cause mortality (adjusted hazard ratio [aHR] 1.73; 95% CI 1.27-2.35) and composite of myocardial infarction, cerebrovascular accident, heart failure, or death (aHR 1.65; 95% CI 1.27-2.15), without significantly increasing the risk for progressive renal decline.
Study details: The data come from a retrospective study including 3333 patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study, of which 83 patients had RA and were taking a disease-modifying antirheumatic therapy.
Disclosures: CRIC study was supported by the US National Institute of Diabetes and Digestive and Kidney Diseases. No conflicts of interest were declared.
Source: Ezeanuna MN et al. Association of rheumatoid arthritis with mortality in chronic kidney disease: a cohort study. Clin Rheumatol. 2022 (May 25). Doi: 10.1007/s10067-022-06223-x
Real-world study evaluates benefits of treat-to-target therapy for BMD loss in RA
Key clinical point: Loss of bone mineral density (BMD) was lower in patients with rheumatoid arthritis (RA) who achieved remission, indicating an important role of treat-to-target therapy in RA, with female sex being a risk factor and low disease activity and bisphosphonate therapy being protective factors.
Major finding: Patients achieving remission had less yearly BMD loss in the lumbar spine (P = .036). Female sex was a risk factor (P = .016), whereas low disease activity (P = .001) and bisphosphonate treatment (P < .001) were protective factors for BMD loss in patients with RA.
Study details: The data comes from a prospective, observational cohort including 268 patients with RA.
Disclosures: This study was supported by the National Natural Science Foundation of China and Peking University Health Science Center. The authors declared no conflicts of interest.
Source: Huang H et al. Impact of treat-to-target therapy on bone mineral density loss in patients with rheumatoid arthritis: A prospective cohort study. Front Endocrinol. 2022;13:867610 (May 17). Doi: 10.3389/fendo.2022.867610
Key clinical point: Loss of bone mineral density (BMD) was lower in patients with rheumatoid arthritis (RA) who achieved remission, indicating an important role of treat-to-target therapy in RA, with female sex being a risk factor and low disease activity and bisphosphonate therapy being protective factors.
Major finding: Patients achieving remission had less yearly BMD loss in the lumbar spine (P = .036). Female sex was a risk factor (P = .016), whereas low disease activity (P = .001) and bisphosphonate treatment (P < .001) were protective factors for BMD loss in patients with RA.
Study details: The data comes from a prospective, observational cohort including 268 patients with RA.
Disclosures: This study was supported by the National Natural Science Foundation of China and Peking University Health Science Center. The authors declared no conflicts of interest.
Source: Huang H et al. Impact of treat-to-target therapy on bone mineral density loss in patients with rheumatoid arthritis: A prospective cohort study. Front Endocrinol. 2022;13:867610 (May 17). Doi: 10.3389/fendo.2022.867610
Key clinical point: Loss of bone mineral density (BMD) was lower in patients with rheumatoid arthritis (RA) who achieved remission, indicating an important role of treat-to-target therapy in RA, with female sex being a risk factor and low disease activity and bisphosphonate therapy being protective factors.
Major finding: Patients achieving remission had less yearly BMD loss in the lumbar spine (P = .036). Female sex was a risk factor (P = .016), whereas low disease activity (P = .001) and bisphosphonate treatment (P < .001) were protective factors for BMD loss in patients with RA.
Study details: The data comes from a prospective, observational cohort including 268 patients with RA.
Disclosures: This study was supported by the National Natural Science Foundation of China and Peking University Health Science Center. The authors declared no conflicts of interest.
Source: Huang H et al. Impact of treat-to-target therapy on bone mineral density loss in patients with rheumatoid arthritis: A prospective cohort study. Front Endocrinol. 2022;13:867610 (May 17). Doi: 10.3389/fendo.2022.867610
Joint-inflammation trajectories differ by SDFR status in ACPA-positive and ACPA-negative RA
Key clinical point: Patients with anticitrullinated peptide antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) show different magnetic resonance imaging-detected joint inflammation trajectories based on the sustained disease-modifying antirheumatic drug (DMARD)-free remission (SDFR) status.
Major finding: Patients with ACPA-positive RA who achieved vs. did not achieve SDFR had lower inflammation levels at disease presentation and subsequent follow-up (P = .02). However, although all patients with ACPA-negative RA had similar inflammation levels at disease presentation, those who achieved vs. did not achieve SDFR had significantly lower inflammation levels in the first year of DMARD treatment (P < .01).
Study details: This study included 198 patients with RA (ACPA-positive [n = 104] and ACPA-negative [n = 94]) treated with DMARD and 174 patients with ACPA-positive RA from the AVERT-1 trial.
Disclosures: The study was funded by the Dutch Arthritis Foundation and the European Research Council. TWJ Huizinga reported receiving research support, lecture fees, and consulting fees from various sources. Two authors reported being shareholders and employees of Bristol Myers Squibb.
Source: Verstappen M et al. ACPA-negative and ACPA-positive RA patients achieving disease resolution demonstrate distinct patterns of MRI-detected joint-inflammation. Rheumatology (Oxford). 2022 (May 18). Doi: 10.1093/rheumatology/keac294
Key clinical point: Patients with anticitrullinated peptide antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) show different magnetic resonance imaging-detected joint inflammation trajectories based on the sustained disease-modifying antirheumatic drug (DMARD)-free remission (SDFR) status.
Major finding: Patients with ACPA-positive RA who achieved vs. did not achieve SDFR had lower inflammation levels at disease presentation and subsequent follow-up (P = .02). However, although all patients with ACPA-negative RA had similar inflammation levels at disease presentation, those who achieved vs. did not achieve SDFR had significantly lower inflammation levels in the first year of DMARD treatment (P < .01).
Study details: This study included 198 patients with RA (ACPA-positive [n = 104] and ACPA-negative [n = 94]) treated with DMARD and 174 patients with ACPA-positive RA from the AVERT-1 trial.
Disclosures: The study was funded by the Dutch Arthritis Foundation and the European Research Council. TWJ Huizinga reported receiving research support, lecture fees, and consulting fees from various sources. Two authors reported being shareholders and employees of Bristol Myers Squibb.
Source: Verstappen M et al. ACPA-negative and ACPA-positive RA patients achieving disease resolution demonstrate distinct patterns of MRI-detected joint-inflammation. Rheumatology (Oxford). 2022 (May 18). Doi: 10.1093/rheumatology/keac294
Key clinical point: Patients with anticitrullinated peptide antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) show different magnetic resonance imaging-detected joint inflammation trajectories based on the sustained disease-modifying antirheumatic drug (DMARD)-free remission (SDFR) status.
Major finding: Patients with ACPA-positive RA who achieved vs. did not achieve SDFR had lower inflammation levels at disease presentation and subsequent follow-up (P = .02). However, although all patients with ACPA-negative RA had similar inflammation levels at disease presentation, those who achieved vs. did not achieve SDFR had significantly lower inflammation levels in the first year of DMARD treatment (P < .01).
Study details: This study included 198 patients with RA (ACPA-positive [n = 104] and ACPA-negative [n = 94]) treated with DMARD and 174 patients with ACPA-positive RA from the AVERT-1 trial.
Disclosures: The study was funded by the Dutch Arthritis Foundation and the European Research Council. TWJ Huizinga reported receiving research support, lecture fees, and consulting fees from various sources. Two authors reported being shareholders and employees of Bristol Myers Squibb.
Source: Verstappen M et al. ACPA-negative and ACPA-positive RA patients achieving disease resolution demonstrate distinct patterns of MRI-detected joint-inflammation. Rheumatology (Oxford). 2022 (May 18). Doi: 10.1093/rheumatology/keac294
Methotrexate reduces risk for mortality in rheumatoid arthritis
Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.
Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).
Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.
Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.
Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031
Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.
Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).
Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.
Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.
Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031
Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.
Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).
Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.
Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.
Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031
Genetic liability to RA and cardiovascular risk: What is the link?
Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.
Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).
Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.
Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.
Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239
Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.
Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).
Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.
Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.
Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239
Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.
Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).
Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.
Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.
Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239
RA: No increased risk for malignancy with tofacitinib vs. TNFi in real world
Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).
Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).
Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.
Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.
Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250
Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).
Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).
Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.
Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.
Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250
Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).
Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).
Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.
Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.
Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250