TBD Meeting (3388-22)

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

Being identified as someone that was advised to stay at home and shield, or keep away from face-to-face interactions with others, during the COVID-19 pandemic was indicative of an increased risk for dying from COVID-19 within 28 days of infection, a U.K. study of inflammatory arthritis patients versus the general population suggests.

In fact, shielding status was the highest ranked of all the risk factors identified for early mortality from COVID-19, with a hazard ratio of 1.52 (95% confidence interval, 1.40-1.64) comparing people with and without inflammatory arthritis (IA) who had tested positive.

The list of risk factors associated with higher mortality in the IA patients versus the general population also included diabetes (HR, 1.38), smoking (HR, 1.27), hypertension (HR, 1.19), glucocorticoid use (HR, 1.17), and cancer (HR, 1.10), as well as increasing age (HR, 1.08) and body mass index (HR, 1.01).

Also important was the person’s prior hospitalization history, with those needing in-hospital care in the year running up to their admission for COVID-19 associated with a 34% higher risk for death, and being hospitalized previously with a serious infection was associated with a 20% higher risk.

This has more to do people’s overall vulnerability than their IA, suggested the team behind the findings, who also found that the risk of catching COVID-19 was significantly lower among patients with IA than the general population (3.5% vs. 6%), presumably because of shielding.

Examining the risks for COVID-19 in real-life practice

“COVID-19 has caused over 10 million deaths,” Roxanne Cooksey, PhD, said at the annual meeting of the British Society for Rheumatology. “It’s greatly affected vulnerable individuals, which includes individuals with IA, this is due to their compromised immune system and increased risk of infection and the medications that they take to manage their conditions.

“Previous studies have had mixed results about whether people with IA have an increased risk of poor outcome,” added Dr. Cooksey, who is a postdoctoral researcher in the division of infection and immunity at Cardiff (Wales) University.

“So, our research question looks to investigate inflammatory arthritis – that’s rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis – to see whether the conditions themselves or indeed their medications predispose individuals to an increased risk of contracting COVID or even more adverse outcomes.”

Dr. Cooksey and colleagues looked specifically at COVID-19 infection rates and outcomes in adults living in Wales during the first year of the pandemic (March 2020 to May 2021). As such they used routinely collected, anonymized health data from the SAIL Databank and performed a retrospective, population-based cohort study. In total, there were 1,966 people with inflammatory arthritis identified as having COVID-19 and 166,602 people without IA but who had COVID-19 in the study population.

As might be expected, people with inflammatory arthritis who tested positive for COVID-19 were older than those testing positive in the general population, at a mean of 62 years versus 46 years. They were also more likely to have been advised to shield (49.4% versus 4.6%), which in the United Kingdom constituted of receiving a letter telling them about the importance of social distancing, wearing a mask when out in public, and quarantining themselves at home whenever possible.

The main outcomes were hospitalizations and mortality within 28 days of COVID-19 infection. Considering the overall inflammatory arthritis population, rates of both outcomes were higher versus the general population. And when the researchers analyzed the risks according to the type of inflammatory arthritis, the associations were not statistically significant in a multivariable analysis for people with any of the inflammatory arthritis diagnoses: rheumatoid arthritis (n = 1,283), psoriatic arthritis (n = 514), or ankylosing spondylitis (n = 246). Some patients had more than one inflammatory arthritis diagnosis.
 

What does this all mean?

Dr. Cooksey conceded that there were lots of limitations to the data collected – from misclassification bias to data possibly not have been recorded completely or missing because of the disruption to health care services during the early stages of the pandemic. Patients may have been told to shield but not actually shielded, she observed, and maybe because a lack of testing COVID-19 cases were missed or people could have been asymptomatic or unable to be tested.

“The study supports the role of shielding in inflammatory arthritis,” Dr. Cooksey said, particularly in those with RA and the risk factors associated with an increased risk in death. However, that may not mean the entire population, she suggested, saying that “refining the criteria for shielding will help mitigate the negative effects of the entire IA population.”

Senior team member Ernest Choy, MD, added his thoughts, saying that, rather than giving generic shielding recommendations to all IA patients, not everyone has the same risk, so maybe not everyone needs to shield to the same level.

“Psoriatic arthritis patients and ankylosing spondylitis patients are younger, so they really don’t have as high a risk like patients with rheumatoid arthritis,” he said.

Dr. Choy, who is professor of rheumatology at the Cardiff Institute of Infection & Immunity, commented that it was not surprising to find that a prior serious infection was a risk for COVID-19 mortality. This risk factor was examined because of the known association between biologic use and the risk for serious infection.

Moreover, he said that, “if you have a serious comorbidity that requires you to get admitted to hospital, that is a reflection of your vulnerability.”

Dr. Cooksey and Dr. Choy had no relevant conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.