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Comorbid spondyloarthritis and fibromyalgia lower response to TNF inhibitors
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Comorbid axial spondyloarthritis and fibromyalgia are associated with a lower response to biologic therapy.
Major finding: About 35% vs. 45% of patients who did and did not meet research criteria for fibromyalgia had an ASAS20 response at 3 months.
Study details: Data on 1,750 participants of the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS).
Disclosures: The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
Source: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
Physical therapy, exercise still relevant for ankylosing spondylitis
CAMBRIDGE, MASS. – , according to Angelo Papachristos, an advanced physiotherapist at St. Michaels Hospital in Toronto.
Speaking in an education session at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN), Mr. Papachristos said that therapy should be introduced at diagnosis, individualized, and constantly reevaluated.
“There is no one recommendation,” he said. “Therapy should be monitored and adjusted over time depending on how the patient responds.”
Mr. Papachristos drew attention to two portions of recommendations from the American College of Sports Medicine (ACSM).
First, that scientific evidence demonstrates that the beneficial effects of exercise are indisputable and that the benefits far outweigh the risks.
Second, that a program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor aspects to improve and maintain fitness and health is essential for most adults.
How much exercise to prescribe and when to introduce exercise remains a question.
The ACSM recommends moderate-intensity cardiovascular exercise for 30 minutes or more each day or 150 minutes per week, resistance training, neuromotor exercise, and flexibility training at least twice each week.
In a 2011 literature review published in Arthritis Care & Research, researchers analyzed 12 studies (826 total patients) to find out if exercise had actual potential for patients with ankylosing spondylitis. They used three criteria: whether the programs were designed using ACSM recommendations, if/how physiological responses were measured, and whether adherence to programs was monitored.
Of the 12 trials, 5 included cardiovascular exercise, 5 included strength training, 11 included flexibility, and 4 reported program adherence.
Only one trial met ACSM recommendations for intensity, duration, frequency, and length of exercise period. That trial showed the greatest improvement in aerobic capacity (Arthritis Car Res. 2011 Apr;63[4]:597-603).
“The literature isn’t impressive,” said Mr. Papachristos. “But, that’s because it isn’t uniform. No specific protocol is being followed.”
He compared what he believes is happening with what he believes to be a better alternative.
What he calls the hit-them-with-everything approach includes diagnosis, NSAIDs, biologics, smoking cessation at the same time as exercise that includes posture, swimming, strength, and aerobic conditioning. According to Mr. Papachristos, this approach can lead to patient burnout.
Indeed, research from 2010 published in the Journal of Rheumatology showed that 40% of patients with ankylosing spondylitis said that exercise takes too much time, 60% said that exercise is hard work, 60% reported being fatigued by exercise, and 20% said that their family members did not encourage exercise (J Rheumatol. 2010 Mar 1. doi: 10.3899/jrheum.090655).
To combat burnout and improve patient outcomes, Mr. Papachristos suggested an alternative approach whereby patients would begin with diagnosis and medication, but disease education and a baseline fitness assessment would also be a priority. The first 6-9 months following diagnosis would then be used to evaluate a patient’s home and work/school ergonomic situation to assess needs. During this time, the patient would be introduced to basic exercises for range of motion and flexibility. Throughout this approach, the patient would be consistently reevaluated and, if appropriate, would slowly ramp up exercise efforts. At 12 months, the patients could graduate to core cervical and lumbar strength before reaching cardiovascular and sports recreation at 12-18 months following diagnosis.
Mr. Papachristos concluded that the coordination between physical therapist, primary care provider, and rheumatologist is of the utmost importance.
“It’s just like anything else – if we’re all on the same page, it’s better for the patient,” he said. “Patients should be encouraged on lifestyle and wellness management with the goal of lifelong regular exercise.”
Mr. Papachristos reported having no disclosures.
CAMBRIDGE, MASS. – , according to Angelo Papachristos, an advanced physiotherapist at St. Michaels Hospital in Toronto.
Speaking in an education session at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN), Mr. Papachristos said that therapy should be introduced at diagnosis, individualized, and constantly reevaluated.
“There is no one recommendation,” he said. “Therapy should be monitored and adjusted over time depending on how the patient responds.”
Mr. Papachristos drew attention to two portions of recommendations from the American College of Sports Medicine (ACSM).
First, that scientific evidence demonstrates that the beneficial effects of exercise are indisputable and that the benefits far outweigh the risks.
Second, that a program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor aspects to improve and maintain fitness and health is essential for most adults.
How much exercise to prescribe and when to introduce exercise remains a question.
The ACSM recommends moderate-intensity cardiovascular exercise for 30 minutes or more each day or 150 minutes per week, resistance training, neuromotor exercise, and flexibility training at least twice each week.
In a 2011 literature review published in Arthritis Care & Research, researchers analyzed 12 studies (826 total patients) to find out if exercise had actual potential for patients with ankylosing spondylitis. They used three criteria: whether the programs were designed using ACSM recommendations, if/how physiological responses were measured, and whether adherence to programs was monitored.
Of the 12 trials, 5 included cardiovascular exercise, 5 included strength training, 11 included flexibility, and 4 reported program adherence.
Only one trial met ACSM recommendations for intensity, duration, frequency, and length of exercise period. That trial showed the greatest improvement in aerobic capacity (Arthritis Car Res. 2011 Apr;63[4]:597-603).
“The literature isn’t impressive,” said Mr. Papachristos. “But, that’s because it isn’t uniform. No specific protocol is being followed.”
He compared what he believes is happening with what he believes to be a better alternative.
What he calls the hit-them-with-everything approach includes diagnosis, NSAIDs, biologics, smoking cessation at the same time as exercise that includes posture, swimming, strength, and aerobic conditioning. According to Mr. Papachristos, this approach can lead to patient burnout.
Indeed, research from 2010 published in the Journal of Rheumatology showed that 40% of patients with ankylosing spondylitis said that exercise takes too much time, 60% said that exercise is hard work, 60% reported being fatigued by exercise, and 20% said that their family members did not encourage exercise (J Rheumatol. 2010 Mar 1. doi: 10.3899/jrheum.090655).
To combat burnout and improve patient outcomes, Mr. Papachristos suggested an alternative approach whereby patients would begin with diagnosis and medication, but disease education and a baseline fitness assessment would also be a priority. The first 6-9 months following diagnosis would then be used to evaluate a patient’s home and work/school ergonomic situation to assess needs. During this time, the patient would be introduced to basic exercises for range of motion and flexibility. Throughout this approach, the patient would be consistently reevaluated and, if appropriate, would slowly ramp up exercise efforts. At 12 months, the patients could graduate to core cervical and lumbar strength before reaching cardiovascular and sports recreation at 12-18 months following diagnosis.
Mr. Papachristos concluded that the coordination between physical therapist, primary care provider, and rheumatologist is of the utmost importance.
“It’s just like anything else – if we’re all on the same page, it’s better for the patient,” he said. “Patients should be encouraged on lifestyle and wellness management with the goal of lifelong regular exercise.”
Mr. Papachristos reported having no disclosures.
CAMBRIDGE, MASS. – , according to Angelo Papachristos, an advanced physiotherapist at St. Michaels Hospital in Toronto.
Speaking in an education session at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN), Mr. Papachristos said that therapy should be introduced at diagnosis, individualized, and constantly reevaluated.
“There is no one recommendation,” he said. “Therapy should be monitored and adjusted over time depending on how the patient responds.”
Mr. Papachristos drew attention to two portions of recommendations from the American College of Sports Medicine (ACSM).
First, that scientific evidence demonstrates that the beneficial effects of exercise are indisputable and that the benefits far outweigh the risks.
Second, that a program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor aspects to improve and maintain fitness and health is essential for most adults.
How much exercise to prescribe and when to introduce exercise remains a question.
The ACSM recommends moderate-intensity cardiovascular exercise for 30 minutes or more each day or 150 minutes per week, resistance training, neuromotor exercise, and flexibility training at least twice each week.
In a 2011 literature review published in Arthritis Care & Research, researchers analyzed 12 studies (826 total patients) to find out if exercise had actual potential for patients with ankylosing spondylitis. They used three criteria: whether the programs were designed using ACSM recommendations, if/how physiological responses were measured, and whether adherence to programs was monitored.
Of the 12 trials, 5 included cardiovascular exercise, 5 included strength training, 11 included flexibility, and 4 reported program adherence.
Only one trial met ACSM recommendations for intensity, duration, frequency, and length of exercise period. That trial showed the greatest improvement in aerobic capacity (Arthritis Car Res. 2011 Apr;63[4]:597-603).
“The literature isn’t impressive,” said Mr. Papachristos. “But, that’s because it isn’t uniform. No specific protocol is being followed.”
He compared what he believes is happening with what he believes to be a better alternative.
What he calls the hit-them-with-everything approach includes diagnosis, NSAIDs, biologics, smoking cessation at the same time as exercise that includes posture, swimming, strength, and aerobic conditioning. According to Mr. Papachristos, this approach can lead to patient burnout.
Indeed, research from 2010 published in the Journal of Rheumatology showed that 40% of patients with ankylosing spondylitis said that exercise takes too much time, 60% said that exercise is hard work, 60% reported being fatigued by exercise, and 20% said that their family members did not encourage exercise (J Rheumatol. 2010 Mar 1. doi: 10.3899/jrheum.090655).
To combat burnout and improve patient outcomes, Mr. Papachristos suggested an alternative approach whereby patients would begin with diagnosis and medication, but disease education and a baseline fitness assessment would also be a priority. The first 6-9 months following diagnosis would then be used to evaluate a patient’s home and work/school ergonomic situation to assess needs. During this time, the patient would be introduced to basic exercises for range of motion and flexibility. Throughout this approach, the patient would be consistently reevaluated and, if appropriate, would slowly ramp up exercise efforts. At 12 months, the patients could graduate to core cervical and lumbar strength before reaching cardiovascular and sports recreation at 12-18 months following diagnosis.
Mr. Papachristos concluded that the coordination between physical therapist, primary care provider, and rheumatologist is of the utmost importance.
“It’s just like anything else – if we’re all on the same page, it’s better for the patient,” he said. “Patients should be encouraged on lifestyle and wellness management with the goal of lifelong regular exercise.”
Mr. Papachristos reported having no disclosures.
REPORTING FROM SPARTAN
Certolizumab pegol shows promise for nr-axSpA treatment
Certolizumab pegol was effective at treating nonradiographic axial spondyloarthritis, the first drug to show positive results with the disease, according to topline data from a phase 3, placebo-controlled trial.
After 52 weeks, 47.2% of adult nonradiographic axial spondyloarthritis (nr-axSpA) patients within the C-AXSPAND trial who received certolizumab pegol (Cimzia) achieved at least a 2-point improvement on their Ankylosing Spondylitis Disease Activity Score, compared with 7.0% of nr-axSpA patients who received a placebo. In addition, patients who received certolizumab pegol also met the Assessment of Spondyloarthritis International Society criteria of 40% response after 12 weeks.
“People living with nr-axSpA frequently face delayed or incorrect diagnosis, and currently, in the U.S., there are no FDA-approved options to treat this condition. The C-AXSPAND study results provide important insights into the potential of Cimzia as an effective and durable treatment option for these patients,” Atul Deodhar, MD, professor of medicine at Oregon Health and Science University, Portland, and a lead investigator of the study, said in an announcement from certolizumab’s manufacturer, UCB.
Certolizumab pegol is currently indicated for the treatment of moderate to severe RA, active psoriatic arthritis, and active ankylosing spondylitis, as well as for the reduction of Crohn’s disease symptoms. The most common adverse events in RA, psoriatic arthritis, and ankylosing spondylitis are upper respiratory tract infection, headache, hypertension, nasopharyngitis, back pain, pyrexia, pharyngitis, and rash.
Certolizumab pegol was effective at treating nonradiographic axial spondyloarthritis, the first drug to show positive results with the disease, according to topline data from a phase 3, placebo-controlled trial.
After 52 weeks, 47.2% of adult nonradiographic axial spondyloarthritis (nr-axSpA) patients within the C-AXSPAND trial who received certolizumab pegol (Cimzia) achieved at least a 2-point improvement on their Ankylosing Spondylitis Disease Activity Score, compared with 7.0% of nr-axSpA patients who received a placebo. In addition, patients who received certolizumab pegol also met the Assessment of Spondyloarthritis International Society criteria of 40% response after 12 weeks.
“People living with nr-axSpA frequently face delayed or incorrect diagnosis, and currently, in the U.S., there are no FDA-approved options to treat this condition. The C-AXSPAND study results provide important insights into the potential of Cimzia as an effective and durable treatment option for these patients,” Atul Deodhar, MD, professor of medicine at Oregon Health and Science University, Portland, and a lead investigator of the study, said in an announcement from certolizumab’s manufacturer, UCB.
Certolizumab pegol is currently indicated for the treatment of moderate to severe RA, active psoriatic arthritis, and active ankylosing spondylitis, as well as for the reduction of Crohn’s disease symptoms. The most common adverse events in RA, psoriatic arthritis, and ankylosing spondylitis are upper respiratory tract infection, headache, hypertension, nasopharyngitis, back pain, pyrexia, pharyngitis, and rash.
Certolizumab pegol was effective at treating nonradiographic axial spondyloarthritis, the first drug to show positive results with the disease, according to topline data from a phase 3, placebo-controlled trial.
After 52 weeks, 47.2% of adult nonradiographic axial spondyloarthritis (nr-axSpA) patients within the C-AXSPAND trial who received certolizumab pegol (Cimzia) achieved at least a 2-point improvement on their Ankylosing Spondylitis Disease Activity Score, compared with 7.0% of nr-axSpA patients who received a placebo. In addition, patients who received certolizumab pegol also met the Assessment of Spondyloarthritis International Society criteria of 40% response after 12 weeks.
“People living with nr-axSpA frequently face delayed or incorrect diagnosis, and currently, in the U.S., there are no FDA-approved options to treat this condition. The C-AXSPAND study results provide important insights into the potential of Cimzia as an effective and durable treatment option for these patients,” Atul Deodhar, MD, professor of medicine at Oregon Health and Science University, Portland, and a lead investigator of the study, said in an announcement from certolizumab’s manufacturer, UCB.
Certolizumab pegol is currently indicated for the treatment of moderate to severe RA, active psoriatic arthritis, and active ankylosing spondylitis, as well as for the reduction of Crohn’s disease symptoms. The most common adverse events in RA, psoriatic arthritis, and ankylosing spondylitis are upper respiratory tract infection, headache, hypertension, nasopharyngitis, back pain, pyrexia, pharyngitis, and rash.
MACE risk similar across arthritis subtypes
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Risk of major adverse cardiovascular events (MACE) was similar for patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.
Major finding: For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. The older age of patients with rheumatoid arthritis explained most of their elevated absolute risk.
Study details: Population-based cohort study of 5,315 patients.
Disclosures: Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
Source: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Reassurance for women taking certolizumab during pregnancy
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Certolizumab use during pregnancy does not appear to increase the risk of congenital malformations.
Major finding: The incidence of fetal death and congenital malformations in certolizumab-exposed pregnancies is similar to that in the general population.
Study details: A prospective and retrospective analysis of data from 528 certolizumab-exposed pregnancies.
Disclosures: The study was funded by UCB Pharma. One author was a contractor for UCB Pharma, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
Source: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508
TB in 2017: Good news and bad news
according to the Centers for Disease Control and Prevention.
Those new lows – TB incidence of 2.8 per 100,000 persons and 9,093 new cases – continue a downward trend that started in 1993, but the current rate of decline is much lower than the threshold needed to eliminate TB by the year 2100, Rebekah J. Stewart and her associates at the CDC’s Division of Tuberculosis Elimination, Atlanta, wrote in the Morbidity and Mortality Weekly Report.
Geographically, at least, the states with populations at the highest risk are Hawaii, which had a TB incidence of 8.1 per 100,000 persons in 2017, and Alaska, with an incidence of 7.0 per 100,000. California and the District of Columbia were next, each with an incidence of 5.2. The states with the lowest rates were Montana and Wyoming at 0.3 per 100,000, the investigators reported, based on data from the National Tuberculosis Surveillance System as of Feb. 12, 2018.
Groups most affected by TB include persons housed in congregate settings – homeless shelters, long-term care facilities, and correctional facilities – and those from countries that have high TB prevalence. Overall incidence for non–U.S. born residents was 14.6 per 100,000 in 2017, compared with 1.0 for the native born, with large discrepancies seen between U.S. and non–U.S. born blacks (2.8 vs. 22.0), native Hawaiian/Pacific Islanders (6.5 vs. 21.0), and Asians (2.0 vs. 27.0), Ms. Stewart and her associates said.
“Increased support of global TB elimination efforts would help to reduce global … prevalence, thereby indirectly reducing the incidence of reactivation TB in the United States among non–U.S. born persons from higher-prevalence countries,” they wrote.
The issue of global action on TB was addressed by the Forum of International Respiratory Societies in a statement recognizing World TB Day (March 24). “TB is the world’s most common infectious disease killer, yet is identifiable, treatable and preventable; what is missing is the political will to dedicate the resources necessary to eradicate it, once and for all,” said Dean E. Schraufnagel, MD, the organization’s executive director.
SOURCE: Stewart RJ et al. MMWR 2018 Mar 23;67(11):317-23.
according to the Centers for Disease Control and Prevention.
Those new lows – TB incidence of 2.8 per 100,000 persons and 9,093 new cases – continue a downward trend that started in 1993, but the current rate of decline is much lower than the threshold needed to eliminate TB by the year 2100, Rebekah J. Stewart and her associates at the CDC’s Division of Tuberculosis Elimination, Atlanta, wrote in the Morbidity and Mortality Weekly Report.
Geographically, at least, the states with populations at the highest risk are Hawaii, which had a TB incidence of 8.1 per 100,000 persons in 2017, and Alaska, with an incidence of 7.0 per 100,000. California and the District of Columbia were next, each with an incidence of 5.2. The states with the lowest rates were Montana and Wyoming at 0.3 per 100,000, the investigators reported, based on data from the National Tuberculosis Surveillance System as of Feb. 12, 2018.
Groups most affected by TB include persons housed in congregate settings – homeless shelters, long-term care facilities, and correctional facilities – and those from countries that have high TB prevalence. Overall incidence for non–U.S. born residents was 14.6 per 100,000 in 2017, compared with 1.0 for the native born, with large discrepancies seen between U.S. and non–U.S. born blacks (2.8 vs. 22.0), native Hawaiian/Pacific Islanders (6.5 vs. 21.0), and Asians (2.0 vs. 27.0), Ms. Stewart and her associates said.
“Increased support of global TB elimination efforts would help to reduce global … prevalence, thereby indirectly reducing the incidence of reactivation TB in the United States among non–U.S. born persons from higher-prevalence countries,” they wrote.
The issue of global action on TB was addressed by the Forum of International Respiratory Societies in a statement recognizing World TB Day (March 24). “TB is the world’s most common infectious disease killer, yet is identifiable, treatable and preventable; what is missing is the political will to dedicate the resources necessary to eradicate it, once and for all,” said Dean E. Schraufnagel, MD, the organization’s executive director.
SOURCE: Stewart RJ et al. MMWR 2018 Mar 23;67(11):317-23.
according to the Centers for Disease Control and Prevention.
Those new lows – TB incidence of 2.8 per 100,000 persons and 9,093 new cases – continue a downward trend that started in 1993, but the current rate of decline is much lower than the threshold needed to eliminate TB by the year 2100, Rebekah J. Stewart and her associates at the CDC’s Division of Tuberculosis Elimination, Atlanta, wrote in the Morbidity and Mortality Weekly Report.
Geographically, at least, the states with populations at the highest risk are Hawaii, which had a TB incidence of 8.1 per 100,000 persons in 2017, and Alaska, with an incidence of 7.0 per 100,000. California and the District of Columbia were next, each with an incidence of 5.2. The states with the lowest rates were Montana and Wyoming at 0.3 per 100,000, the investigators reported, based on data from the National Tuberculosis Surveillance System as of Feb. 12, 2018.
Groups most affected by TB include persons housed in congregate settings – homeless shelters, long-term care facilities, and correctional facilities – and those from countries that have high TB prevalence. Overall incidence for non–U.S. born residents was 14.6 per 100,000 in 2017, compared with 1.0 for the native born, with large discrepancies seen between U.S. and non–U.S. born blacks (2.8 vs. 22.0), native Hawaiian/Pacific Islanders (6.5 vs. 21.0), and Asians (2.0 vs. 27.0), Ms. Stewart and her associates said.
“Increased support of global TB elimination efforts would help to reduce global … prevalence, thereby indirectly reducing the incidence of reactivation TB in the United States among non–U.S. born persons from higher-prevalence countries,” they wrote.
The issue of global action on TB was addressed by the Forum of International Respiratory Societies in a statement recognizing World TB Day (March 24). “TB is the world’s most common infectious disease killer, yet is identifiable, treatable and preventable; what is missing is the political will to dedicate the resources necessary to eradicate it, once and for all,” said Dean E. Schraufnagel, MD, the organization’s executive director.
SOURCE: Stewart RJ et al. MMWR 2018 Mar 23;67(11):317-23.
FROM MMWR
Axial SpA disease activity remains mostly stable throughout pregnancy
, according to results of a prospective study.
“In the largest prospective study to date exploring disease activity during pregnancy in women with axSpA, we found that the majority experienced stable, low disease activity,” Kristin Ursin, MD, of the Trondheim (Norway) University Hospital and her associates wrote in Rheumatology. “In accordance with two previous studies, we found a small increase in disease activity in the second trimester.”
All women in the study fulfilled the Assessment of SpondyloArthritis International Society criteria for axSpA and had seven clinic visits throughout their pregnancy: one before conception, one at each trimester, another at 6 weeks, and two visits 6 and 12 months after delivery. No differentiation was made between women with radiographic or nonradiographic axSpA. At each visit, patients’ disease activity was determined using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which is calculated based on six patient factors scored from 1 to 10, including: fatigue, back pain, peripheral joint pain and swelling, localized tenderness, duration of morning stiffness, and severity of morning stiffness. A disease score of 4 is commonly used to define active disease. Disease activity was also assessed by measuring C-reactive protein (CRP). Women’s function and health was also assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI), scored similarly to the BASDAI, and the RAND-36 questionnaire to assess general health.
The research team found that, across the span of pregnancy, axSpA disease activity was relatively low and consistent throughout the study. But there was a significant relationship between disease activity and time (P = .029) in which disease activity was highest during the second trimester and proved to be significantly higher than 6 weeks after giving birth (mean BASDAI 3.97 vs. 3.46, P = .005). In fact, 45% of women had active disease in their second trimester (BASDAI of 4 or greater). But among women with data from the second trimester and 6 weeks post partum, 42% had a decrease in BASDAI score of 1 or more, and 22% had an equivalent increase. CRP values remained low and stable throughout the study.
Like the BASDAI scores, physical function and well being seemed to correlate with later time points during pregnancy. The lowest level of physical functioning for most women was during the second and third trimesters, and those periods were significantly worse than 6 weeks after giving birth (mean BASFI of 3.2 during the second trimester and 3.6 during the third vs. 2.6 at 6 weeks post partum). Similarly, patients reported overall worse general health during the second and third trimesters, compared with 6 weeks after giving birth, based on RAND-36 scores (mean physical functioning score of 63.1 in the second trimester and 54.5 in the third vs. 71.0 at 6 weeks post partum).
Use of nonbiologic medications remained relatively stable during pregnancy, while biologic disease-modifying antirheumatic drug (DMARD) use (all tumor necrosis factor [TNF] inhibitors) dropped significantly when pregnancy was confirmed. About 20% used NSAIDs during pregnancy, except for during the third trimester when use decreased to 8%. Prednisolone use remained stable at 5%-8%. A total of 11% had used synthetic DMARDs prior to pregnancy, and this rate stayed at 10%-16% during the three trimesters. Overall, 44% had used a biologic DMARD (TNF inhibitor) prior to pregnancy, but this declined sharply to 6% during the first trimester and 1% in the third.
The main limitations of the study included not having data from all of the women for all the time points. In fact, only 22% were included prior to conceiving, which could suggest that women with low disease activity were less likely to visit their rheumatologist, thereby biasing the sample toward an overestimated disease activity at preconception that could have potentially hidden a “more evident deterioration between the preconception visit and the second trimester,” the authors said.
“Future research on pregnancy in women with axSpA should differentiate between subgroups of the disease and aim to include objective assessment of inflammation.”
The study was funded by the Research Fund of the Norwegian Organization for People With Rheumatic Diseases. None of the authors had any conflicts of interest to declare.
SOURCE: Ursin K et al. Rheumatology. 2018 Mar 14. doi: 10.1093/rheumatology/key047.
, according to results of a prospective study.
“In the largest prospective study to date exploring disease activity during pregnancy in women with axSpA, we found that the majority experienced stable, low disease activity,” Kristin Ursin, MD, of the Trondheim (Norway) University Hospital and her associates wrote in Rheumatology. “In accordance with two previous studies, we found a small increase in disease activity in the second trimester.”
All women in the study fulfilled the Assessment of SpondyloArthritis International Society criteria for axSpA and had seven clinic visits throughout their pregnancy: one before conception, one at each trimester, another at 6 weeks, and two visits 6 and 12 months after delivery. No differentiation was made between women with radiographic or nonradiographic axSpA. At each visit, patients’ disease activity was determined using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which is calculated based on six patient factors scored from 1 to 10, including: fatigue, back pain, peripheral joint pain and swelling, localized tenderness, duration of morning stiffness, and severity of morning stiffness. A disease score of 4 is commonly used to define active disease. Disease activity was also assessed by measuring C-reactive protein (CRP). Women’s function and health was also assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI), scored similarly to the BASDAI, and the RAND-36 questionnaire to assess general health.
The research team found that, across the span of pregnancy, axSpA disease activity was relatively low and consistent throughout the study. But there was a significant relationship between disease activity and time (P = .029) in which disease activity was highest during the second trimester and proved to be significantly higher than 6 weeks after giving birth (mean BASDAI 3.97 vs. 3.46, P = .005). In fact, 45% of women had active disease in their second trimester (BASDAI of 4 or greater). But among women with data from the second trimester and 6 weeks post partum, 42% had a decrease in BASDAI score of 1 or more, and 22% had an equivalent increase. CRP values remained low and stable throughout the study.
Like the BASDAI scores, physical function and well being seemed to correlate with later time points during pregnancy. The lowest level of physical functioning for most women was during the second and third trimesters, and those periods were significantly worse than 6 weeks after giving birth (mean BASFI of 3.2 during the second trimester and 3.6 during the third vs. 2.6 at 6 weeks post partum). Similarly, patients reported overall worse general health during the second and third trimesters, compared with 6 weeks after giving birth, based on RAND-36 scores (mean physical functioning score of 63.1 in the second trimester and 54.5 in the third vs. 71.0 at 6 weeks post partum).
Use of nonbiologic medications remained relatively stable during pregnancy, while biologic disease-modifying antirheumatic drug (DMARD) use (all tumor necrosis factor [TNF] inhibitors) dropped significantly when pregnancy was confirmed. About 20% used NSAIDs during pregnancy, except for during the third trimester when use decreased to 8%. Prednisolone use remained stable at 5%-8%. A total of 11% had used synthetic DMARDs prior to pregnancy, and this rate stayed at 10%-16% during the three trimesters. Overall, 44% had used a biologic DMARD (TNF inhibitor) prior to pregnancy, but this declined sharply to 6% during the first trimester and 1% in the third.
The main limitations of the study included not having data from all of the women for all the time points. In fact, only 22% were included prior to conceiving, which could suggest that women with low disease activity were less likely to visit their rheumatologist, thereby biasing the sample toward an overestimated disease activity at preconception that could have potentially hidden a “more evident deterioration between the preconception visit and the second trimester,” the authors said.
“Future research on pregnancy in women with axSpA should differentiate between subgroups of the disease and aim to include objective assessment of inflammation.”
The study was funded by the Research Fund of the Norwegian Organization for People With Rheumatic Diseases. None of the authors had any conflicts of interest to declare.
SOURCE: Ursin K et al. Rheumatology. 2018 Mar 14. doi: 10.1093/rheumatology/key047.
, according to results of a prospective study.
“In the largest prospective study to date exploring disease activity during pregnancy in women with axSpA, we found that the majority experienced stable, low disease activity,” Kristin Ursin, MD, of the Trondheim (Norway) University Hospital and her associates wrote in Rheumatology. “In accordance with two previous studies, we found a small increase in disease activity in the second trimester.”
All women in the study fulfilled the Assessment of SpondyloArthritis International Society criteria for axSpA and had seven clinic visits throughout their pregnancy: one before conception, one at each trimester, another at 6 weeks, and two visits 6 and 12 months after delivery. No differentiation was made between women with radiographic or nonradiographic axSpA. At each visit, patients’ disease activity was determined using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which is calculated based on six patient factors scored from 1 to 10, including: fatigue, back pain, peripheral joint pain and swelling, localized tenderness, duration of morning stiffness, and severity of morning stiffness. A disease score of 4 is commonly used to define active disease. Disease activity was also assessed by measuring C-reactive protein (CRP). Women’s function and health was also assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI), scored similarly to the BASDAI, and the RAND-36 questionnaire to assess general health.
The research team found that, across the span of pregnancy, axSpA disease activity was relatively low and consistent throughout the study. But there was a significant relationship between disease activity and time (P = .029) in which disease activity was highest during the second trimester and proved to be significantly higher than 6 weeks after giving birth (mean BASDAI 3.97 vs. 3.46, P = .005). In fact, 45% of women had active disease in their second trimester (BASDAI of 4 or greater). But among women with data from the second trimester and 6 weeks post partum, 42% had a decrease in BASDAI score of 1 or more, and 22% had an equivalent increase. CRP values remained low and stable throughout the study.
Like the BASDAI scores, physical function and well being seemed to correlate with later time points during pregnancy. The lowest level of physical functioning for most women was during the second and third trimesters, and those periods were significantly worse than 6 weeks after giving birth (mean BASFI of 3.2 during the second trimester and 3.6 during the third vs. 2.6 at 6 weeks post partum). Similarly, patients reported overall worse general health during the second and third trimesters, compared with 6 weeks after giving birth, based on RAND-36 scores (mean physical functioning score of 63.1 in the second trimester and 54.5 in the third vs. 71.0 at 6 weeks post partum).
Use of nonbiologic medications remained relatively stable during pregnancy, while biologic disease-modifying antirheumatic drug (DMARD) use (all tumor necrosis factor [TNF] inhibitors) dropped significantly when pregnancy was confirmed. About 20% used NSAIDs during pregnancy, except for during the third trimester when use decreased to 8%. Prednisolone use remained stable at 5%-8%. A total of 11% had used synthetic DMARDs prior to pregnancy, and this rate stayed at 10%-16% during the three trimesters. Overall, 44% had used a biologic DMARD (TNF inhibitor) prior to pregnancy, but this declined sharply to 6% during the first trimester and 1% in the third.
The main limitations of the study included not having data from all of the women for all the time points. In fact, only 22% were included prior to conceiving, which could suggest that women with low disease activity were less likely to visit their rheumatologist, thereby biasing the sample toward an overestimated disease activity at preconception that could have potentially hidden a “more evident deterioration between the preconception visit and the second trimester,” the authors said.
“Future research on pregnancy in women with axSpA should differentiate between subgroups of the disease and aim to include objective assessment of inflammation.”
The study was funded by the Research Fund of the Norwegian Organization for People With Rheumatic Diseases. None of the authors had any conflicts of interest to declare.
SOURCE: Ursin K et al. Rheumatology. 2018 Mar 14. doi: 10.1093/rheumatology/key047.
FROM RHEUMATOLOGY
Key clinical point: Higher disease activity and lower physical well being correspond with late stage pregnancy.
Major finding: Disease activity appears to be highest in the second trimester, compared with 6 weeks post partum (mean BASDAI 3.97 vs. 3.46, P = .005).
Study details: A prospective study of 179 pregnancies in 166 Norwegian women with axSpA from a Norwegian health registry between 2006 and 2016.
Disclosures: The study was funded by the Research Fund of the Norwegian Organization for People With Rheumatic Diseases. None of the authors had any conflicts of interest to declare.
Source: Ursin K et al. Rheumatology. 2018 Mar 14. doi: 10.1093/rheumatology/key047.
FDA approves certolizumab label update for pregnancy, breastfeeding
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
The manufacturer of certolizumab pegol, UCB, announced March 22 that the Food and Drug Administration approved a label update to the biologic that includes pharmacokinetic data showing negligible to low transfer of the biologic through the placenta and minimal mother-to-infant transfer from breast milk.
In the CRIB study, certolizumab levels were below the lower limit of quantification (defined as 0.032 mcg/mL) in 13 out of 15 infant blood samples at birth and in all samples at weeks 4 and 8. No anticertolizumab antibodies were detected in mothers, umbilical cords, or infants.
In the CRADLE study, 56% of 137 breast milk samples from 17 mothers had no measurable certolizumab, and the remaining samples showed minimal levels of the biologic. No serious adverse reactions were noted in the 17 infants in the study.
“It is well recognized that women with chronic inflammatory disease face uncertainty during motherhood given the lack of information on treatment during pregnancy and breastfeeding. Many women with chronic inflammatory disease discontinue their biologic treatment during pregnancy, often when they need disease control the most,” said CRADLE lead study author Megan E. B. Clowse, MD, of Duke University, Durham, N.C., in a press release issued by UCB. “These data for Cimzia provide important information to empower women and healthcare providers making decisions about treatment during pregnancy and breastfeeding.”
UCB said that limited data from an ongoing pregnancy registry regarding the use of certolizumab in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes.
Maternal biologic therapy does not affect infant vaccine responses
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
MAUI, HAWAII – The infants of inflammatory bowel disease patients on biologic therapy during pregnancy and breastfeeding do not have a diminished response rate to the inactivated vaccines routinely given during the first 6 months of life, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“Those babies are going to have detectable levels of drug on board, but they respond to vaccines just as well as infants born to mothers with IBD who were not on biologic therapy. The rates are the same, albeit lower than in the general population,” according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
Previous reports from the national registry have established that continuation of biologics in IBD patients throughout pregnancy and breastfeeding to maintain disease control poses no increased risks to the fetus in terms of rates of congenital anomalies, spontaneous abortion, intrauterine growth restriction, low birth weight, or longer-term developmental delay, compared with unexposed babies whose mothers have IBD.
Dr. Ananthakrishnan’s analysis focused on response rates to tetanus and Haemophilus influenzae B vaccines in the infants of 179 PIANO patients. Sixty-five percent of the IBD patients were on various biologic agents during pregnancy, 8% were on a thiopurine, 21% were on combination therapy, and 6% weren’t exposed to any IBD medications. Serologic studies showed that there was no difference across the four groups in terms of infant rates of protective titers in response to the vaccines. However, the 69%-84% rates of protective titers in the four groups fell short of the 90%-plus rate expected in the general population.
Live virus vaccines are contraindicated in the first 6 months of life in infants exposed to maternal biologics in utero. The only live virus vaccine given during that time frame in the United States is rotavirus, administered at months 2 and 3. Dr. Mahadevan and others recommend skipping that vaccine in babies exposed in utero to any IBD biologic other than certolizumab pegol (Cimzia), which uniquely doesn’t cross the placenta.
“That being said, infants born to 71 of our PIANO participants on anti-TNF therapy in pregnancy inadvertently got the rotavirus vaccine, and they were all just fine, even with very high drug levels,” the gastroenterologist said.
The live virus varicella and MMR vaccines can safely be given as scheduled at 1 year of age. By that time the biologics are long gone from the child.
Dr. Mahadevan reported receiving research funding from the Crohn’s and Colitis Foundation of America, which sponsors the PIANO registry. She also has financial relationships with several pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
How to direct refer for GI endoscopy
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018