Becky McCall

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

GHENT, BELGIUM – Patients with nonradiographic or radiographic axial spondyloarthritis (axSpA) experienced clinically relevant treatment responses to bimekizumab (Bimzelx) at similar rates that significantly exceeded placebo, regardless of prior experience with a tumor necrosis factor (TNF) inhibitor, according to results from two phase 3 trials presented at the 13th International Congress on Spondyloarthritides.

In addition, around half of patients with either nonradiographic or radiographic disease achieved complete remission of enthesitis by week 16 of treatment with bimekizumab. The drug, a humanized, monoclonal antibody dually inhibiting interleukins (IL) 17A and 17F, is approved in the European Union for treating adults with moderate to severe plaque psoriasis.

Becky McCall/MDedge News

“Bimekizumab blockade works independently of axial spondyloarthritis pretreatment, which means this drug specifically blocks something that other drugs do not reach,” said Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany). He presented 24-week data on the use of bimekizumab.

The BE MOBILE 1 trial involved 256 patients with nonradiographic axSpA, whereas BE MOBILE 2 involved 232 patients with radiographic axSpA. In both trials, bimekizumab 160 mg was administered subcutaneously every 4 weeks, and at week 16, all patients, including those who had received placebo, received open-label bimekizumab for another 8 weeks. This news organization previously reported results from BE MOBILE 2 that were presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 annual meeting.

In Ghent, referring to the nonradiographic patients, Dr. Baraliakos said in an interview, “We saw a very clear response to the active drug even after 2 weeks. The curves separated out from placebo. The week 16 primary analysis showed patients on bimekizumab did significantly better, [and there was] a similar response in those who switched to [open-label] bimekizumab after placebo” at week 16.

In patients with nonradiographic disease at week 24, 52.3% on bimekizumab achieved the trial’s primary outcome of 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40), compared with 46.8% of patients who were receiving placebo and then switched to open-label bimekizumab at week 16, the latter rising from 21.4% at week 16. For comparison, 47.7% on bimekizumab achieved ASAS 40 at week 16.

At week 24 in BE MOBILE 2, 53.8% of patients with radiographic disease on continuous bimekizumab met ASAS 40 criteria, as did 56.8% of patients who switched from placebo to open-label bimekizumab, rising from 22.5% with placebo and 44.8% with bimekizumab at week 16.

Audience member Fabian Proft, MD, of Charité Medical University, Berlin, commented on the latest results as well as wider bimekizumab findings, including those relating to psoriasis. “When we compare this to drugs that are already approved and available, we can assume that bimekizumab is equally effective to existing ones,” he said, noting that “there is the additional option in patients with psoriasis, where it seems to be the most effective drug for this indication. If I had a patient with radiographic or nonradiographic axial SpA and who also had significant psoriasis, then bimekizumab would be my choice of treatment.”


 

Targeting IL-17A and IL-17F in one drug

In the BE MOBILE 1 study, Dr. Baraliakos and coinvestigators looked at whether inhibiting IL-17F as well as IL-17A “makes sense” in terms of clinical benefits in patients with axSpA.

“Previous experience with IL-17A inhibitors shows they work well but still miss some patients,” Dr. Baraliakos said, adding that, “the hope is that by blocking both IL-17A and IL-17F, the response will be a bit better in terms of both greater response and longevity of response than [with an] IL-17A [inhibitor] alone.”

Patients in BE MOBILE 1 were typical adult patients with nonradiographic axSpA who fulfilled ASAS classification criteria and had elevated C-reactive protein (CRP) and/or sacroiliitis on MRI. All patients were older than 18 years and had a mean age of 39 years. In each arm, 51%-57% were men. Overall, patients had a mean of 9 years of symptoms and a mean Ankylosing Spondylitis Disease Activity Score of 3.7 in both patient groups (placebo and bimekizumab).

All had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spi­nal pain ≥ 4) at baseline and demonstrated failure to respond to two different NSAIDs or had a history of intolerance to or contraindication to NSAIDs. Patients had previously received up to one TNF inhibitor (13.5% in the placebo group and 7.8% in the bimekizumab group).

The primary outcome compared rate of response to ASAS 40 criteria, which comprises patient global assessment of disease, spinal pain, function (as assessed by the Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (stiffness).

Early response seen regardless of previous TNF inhibitor experience

“We saw response to bimekizumab very early in our patients at 16 weeks. The amount of response was higher than that observed with IL-17A alone,” Dr. Baraliakos said in an interview. “It’s understood that IL-17A and IL-17F do not work together on the inflammatory cascade, but work separately, and this might explain the findings whereby this drug captures more inflammation.”

Dr. Baraliakos highlighted the unique response rates seen with bimekizumab regardless of past TNF inhibitor use. “The TNF inhibitor-experienced patients responded as well as the TNF inhibitor–naive ones. This is unusual because nonresponders to other drugs are usually more severely affected and have a lower chance of showing response to any drug. Also, we did not see this response in patients treated with IL-17A only.”

At 16 weeks, patients with nonradiographic disease without a past history of using a TNF inhibitor had ASAS 40 responses at rates of 46.6% with bimekizumab and 22.9% with placebo. These rates in patients with past TNF inhibitor use were 60% with bimekizumab and 11.8% with placebo.

Statistically significant differences between bimekizumab and placebo occurred for all primary and secondary outcomes. “This includes the MRI inflammation findings in bimekizumab-treated patients,” Dr. Baraliakos reported.

Complete resolution of enthesitis was also observed. By week 24, enthesitis completely resolved in 47.9% of patients with nonradiographic disease on continuous bimekizumab and 43.5% of those patients who switched from placebo to bimekizumab. In patients with radiographic disease, complete resolution occurred in 53% of those on continuous bimekizumab and 49.3% of patients who switched at week 16. “This was an excellent outcome,” Dr. Baraliakos said.

The safety profile at 24 weeks confirmed prior findings at 16 weeks in which the most common treatment-emergent adverse events with bimekizumab were nasopharyngitis (9.4%), upper respiratory tract infection (7%), and oral candidiasis (3.1%); fungal infections overall occurred in 7% taking bimekizumab.

“We saw slightly higher fungal infections, but this is because we block IL-17A and IL-17F, and [the risk for these infections] is linked to the mechanism of action. But we can deal with this,” Dr. Baraliakos said.

The trials were sponsored by UCB. Dr. Baraliakos disclosed serving on the speakers bureau and as a paid instructor and consultant for Ab­bVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Galapagos, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. Dr. Proft disclosed serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; being a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly.

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

Erosions and ankylosis in patients with sacroiliitis are detectable to a high degree of accuracy on CT images using an artificial intelligence (AI)–based algorithm, according to research presented at the 13th International Congress on Spondyloarthritides.

Lennart Jans, MD, head of clinics in musculoskeletal imaging in the department of radiology at Ghent (Belgium) University Hospital, shared data on the development and validation of the algorithm for automatic detection of erosion and ankylosis on CT images of the sacroiliac (SI) joints.

Becky McCall/MDedge News

“Essentially, in terms of statistics, this AI algorithm has 95% sensitivity for picking up erosions in patients with clinical symptoms of sacroiliitis, and if this is further developed as a tool, it could aid detection in people with erosions that would otherwise go undetected and undiagnosed,” Dr. Jans said in an interview, stressing that the results were still preliminary.

“We want to move from reporting one patient at a time to a system that detects and helps to diagnose larger numbers of patients and makes a larger impact on patient outcomes.”

He stressed that, with thousands of images per patient, it is an impossible workload for any radiology department to read every image necessary to inform diagnoses, and this is only exacerbated by the shortage of rheumatologists, especially in the United States.

Denis Poddubnyy, MD, head of rheumatology at Charité University Hospital, Berlin, acknowledged that AI has potential to improve the recognition of changes indicative of spondyloarthritis (SpA) on imaging. “A standardized, valid, and reliable detection of those changes is relevant for both diagnosis, including differential diagnosis, and classification of SpA.”

Dr. Poddubnyy added that the AI-based algorithm developed by Dr. Jans and associates is designed to detect very specific SpA structural changes in the SI joints on CT. “CT is usually applied in the clinical practice after MRI ... normally in cases where MRI does not provide conclusive results,” he said. Since MRI scans have also been recently used to develop an AI-based algorithm for the detection of active inflammation – not captured by CT – and structural changes in SI joints, he noted that the “generated data on CT should be, therefore, seen in a broader context toward standardization of imaging findings detection.”
 

Proof-of-concept findings are due for scale-up

Dr. Jans acknowledged that the current data only establish proof of concept. Among the study’s 145 patients, 60% were used for training the AI algorithm and 40% for testing it. All patients who had clinical symptoms of sacroiliitis and had undergone a SI joint CT scan were included from two hospitals: Ghent University Hospital and the University of Alberta Hospital, Edmonton. The majority of patients were female (81 of 145). They had a mean age of 40 years, 84 had diagnosed axial SpA, 15 had mechanical back pain, and 46 did not have a final diagnosis.

CT images were examined by three independent and blinded radiologists who annotated erosions more than 1 mm and ankylosis more than 2 mm, while a type of AI algorithm known as a neural network pipeline was developed to segment the SI joints and detect structural lesions.

In the first instance, Dr. Jans explained, examination of CT images using the AI algorithm from patients who enter the hospital for other reasons, such as trauma, rheumatic diseases, kidney stones, or appendicitis, might lead to the detection of otherwise unknown erosions. “Often patients have complained of backache for years, seeing various physiotherapists and similar, but had no idea what might be causing it,” he said. “We just don’t have the time for examining all the thousands of images separately. We need some kind of aid here. We need an extra pair of eyes. This is what AI software does.”

Dr. Jans said rheumatologists who ultimately want to detect and diagnose patients with SI erosions want to reduce the false-negative findings. “They want the system to pick up all the patients who have erosions. Here, the most important parameter is sensitivity, and we find that our algorithm shows a very high sensitivity. Optimization of the AI algorithm to reduce false negatives resulted in a sensitivity of 95% for detection of erosions on CT of the sacroiliac joints on a patient level.”

While overall accuracy was over 90%, Dr. Jans acknowledged that the algorithm was run in a relatively select population of dedicated CT scans of the joints. He is also aware that a good AI algorithm needs to work well across locations and populations. “If you make something within your institution alone, it will not work in a hospital on the other side of the street.”

However, he added, the researchers used images from four different CT scanners and images from two different institutions – one in Canada and their own in Belgium, providing a case mix that makes their algorithm more refined.
 

Next step: Test in an unselected population

When asked to comment on the study, Mikael Boesen, MD, PhD, of Bispebjerg and Frederiksberg Hospital, Copenhagen, congratulated Dr. Jans on the work and remarked that he found the research potentially clinically useful.

“The next steps would be to test the performance of the model in an unselected population of patients who have CT scans of the abdomen for other reasons to test the model’s ability to flag potential SI joint disease to the reader, which is often overlooked, as well as [to see] how the model performs in larger datasets from other hospitals, vendors, and CT-reconstruction algorithms.”

Finally, Dr. Boesen pointed out that it would be interesting to see if the AI algorithm can detect different reasons for erosions. “Especially [for] separation between mechanical and inflammatory courses. This could potentially be done by automatically mapping the location of the erosions in the SI joints.”

Dr. Jans has now opened up the project to other radiologists to collaborate and provide images to train and test the algorithm further. “We now have 2.4 million images that have been enriched, and we will use these in the near future as we move beyond the proof-of-concept stage.

He is looking for as for as many partners as possible to help collect enriched images and develop this into a real tool for use in hospitals worldwide on clinical patients. “We have joined forces with several hospitals but continue looking for further collaborations.

“We need, just like self-driving cars, not just thousands, but tens of thousands or millions of images to develop this.”

Dr. Jans declared receiving speaker fees from UCB, AbbVie, Lilly, and Novartis, and that he is cofounder of a future spin-off of Ghent University RheumaFinder. Dr. Poddubnyy and Dr. Boesen declared no relevant disclosures.
 

Gynecologic and obstetric health care needs of transgender and gender-diverse adults, including fertility preservation, ending masculinizing hormones in pregnancy, and support for “chest-feeding” are proposed in a novel draft guideline issued by the U.K.’s Royal College of Obstetricians and Gynaecologists.

The draft Green-top Guideline on Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is open for consultation and comment until Sept. 6. It aims to address the specific needs of transgender and gender-diverse individuals that, according to the guideline, are currently not consistently included in specialist training programs or in continuing professional development.

With a rise in the number of people seeking to transition, obstetricians and gynecologists are seeing more transgender and gender-diverse patients. Phil Rolland, MD, consultant gynecological oncologist from Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, and member of the guideline committee, said that, “It is highly likely that if an obstetrician or gynaecologist hasn’t already consulted or treated a trans or gender-diverse patient then it is only a matter of time before they do.”

He stressed the importance of ensuring inclusivity in obstetric and gynecologic care. “We know that trans people are more likely to have poor experiences when accessing health care, and we can do better.”

The U.K.-based guideline follows a similar document from the American College of Obstetricians and Gynecologists, put in place in March 2021, as reported by this news organization. It called for greater “awareness, knowledge, and sensitivity” in caring for these patients and noted that “bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients.”
 

Guideline addresses fertility preservation, obstetric care, and more

Regarding fertility preservation, discussions around protecting future options should be held before endocrine interventions and/or gender-affirming genital or pelvic surgery procedures, says the guideline. In addition, gynecologic problems that can be experienced need to be explained.

The guideline also addresses obstetric care, advising that trans men on long-acting masculinizing hormone therapy should stop therapy 3 months prior to conception. People who conceive while taking masculinizing hormone therapy should discontinue the therapy as soon as possible.

Birth mode should be discussed with all trans men who plan to conceive, ideally at a prepregnancy counseling appointment, but at minimum, before the third trimester. Choice of feeding manner should also be addressed in the antenatal period, with trans men who wish to chest feed offered chest-feeding support, similar to that given to cis women.

The RCOG guideline comes in the wake of the U.K. government’s new Women’s Health Strategy for England, released in July, which notes that trans men (with female reproductive organs) should be able to access screening services for cervical and breast cancer, a position upheld by the RCOG guideline.

Other key recommendations include that obstetricians and gynecologists, when approached by transgender and gender-diverse people to help with identity-related issues, should liaise with gender-identity specialist services to provide appropriate care.
 

Removing bias, providing affirming care

Asha Kasliwal, MD, consultant in Community Gynaecology and Reproductive Health Care, Manchester, England, and president of the Faculty of Sexual and Reproductive Healthcare, also reflected on how transgender and gender-diverse people often feel uncomfortable accessing care, which could lead to, “many people failing to seek or continue health care because of concerns over how they will be treated,” adding that there were associated reports of poor clinical outcomes.

She highlighted that the draft guideline pointed out the importance of language during consultation with transgender and gender-diverse people, noting that “misuse of language, and particularly deliberate misuse of language associated with the sex assigned at birth (misgendering), may cause profound offence.”

Dr. Kasliwal cited the example of “using the correct pronouns when addressing someone and receiving any information about a person’s gender diversity neutrally and nonjudgementally.”

Edward Morris, MD, president of the Royal College of Obstetricians and Gynaecologists, acknowledged that trans and gender-diverse individuals say they often feel judged and misunderstood by the health service. “This can act as a barrier for them when it comes to accessing vital care, and we as health care professionals have a role to play in making them feel listened to and recognized.”

“This draft guideline is our first attempt to ensure we are providing personalised care for all our patients,” said Dr. Morris. “We welcome feedback on this draft to ensure the guideline is the best as it can be for clinicians and the trans and gender-diverse individuals who use our services.”

The draft guideline as peer-review draft, Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is available on the RCOG website. Consultation is open until Sept. 6, 2022.

A version of this article first appeared on Medscape.com.

Gynecologic and obstetric health care needs of transgender and gender-diverse adults, including fertility preservation, ending masculinizing hormones in pregnancy, and support for “chest-feeding” are proposed in a novel draft guideline issued by the U.K.’s Royal College of Obstetricians and Gynaecologists.

The draft Green-top Guideline on Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is open for consultation and comment until Sept. 6. It aims to address the specific needs of transgender and gender-diverse individuals that, according to the guideline, are currently not consistently included in specialist training programs or in continuing professional development.

With a rise in the number of people seeking to transition, obstetricians and gynecologists are seeing more transgender and gender-diverse patients. Phil Rolland, MD, consultant gynecological oncologist from Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, and member of the guideline committee, said that, “It is highly likely that if an obstetrician or gynaecologist hasn’t already consulted or treated a trans or gender-diverse patient then it is only a matter of time before they do.”

He stressed the importance of ensuring inclusivity in obstetric and gynecologic care. “We know that trans people are more likely to have poor experiences when accessing health care, and we can do better.”

The U.K.-based guideline follows a similar document from the American College of Obstetricians and Gynecologists, put in place in March 2021, as reported by this news organization. It called for greater “awareness, knowledge, and sensitivity” in caring for these patients and noted that “bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients.”
 

Guideline addresses fertility preservation, obstetric care, and more

Regarding fertility preservation, discussions around protecting future options should be held before endocrine interventions and/or gender-affirming genital or pelvic surgery procedures, says the guideline. In addition, gynecologic problems that can be experienced need to be explained.

The guideline also addresses obstetric care, advising that trans men on long-acting masculinizing hormone therapy should stop therapy 3 months prior to conception. People who conceive while taking masculinizing hormone therapy should discontinue the therapy as soon as possible.

Birth mode should be discussed with all trans men who plan to conceive, ideally at a prepregnancy counseling appointment, but at minimum, before the third trimester. Choice of feeding manner should also be addressed in the antenatal period, with trans men who wish to chest feed offered chest-feeding support, similar to that given to cis women.

The RCOG guideline comes in the wake of the U.K. government’s new Women’s Health Strategy for England, released in July, which notes that trans men (with female reproductive organs) should be able to access screening services for cervical and breast cancer, a position upheld by the RCOG guideline.

Other key recommendations include that obstetricians and gynecologists, when approached by transgender and gender-diverse people to help with identity-related issues, should liaise with gender-identity specialist services to provide appropriate care.
 

Removing bias, providing affirming care

Asha Kasliwal, MD, consultant in Community Gynaecology and Reproductive Health Care, Manchester, England, and president of the Faculty of Sexual and Reproductive Healthcare, also reflected on how transgender and gender-diverse people often feel uncomfortable accessing care, which could lead to, “many people failing to seek or continue health care because of concerns over how they will be treated,” adding that there were associated reports of poor clinical outcomes.

She highlighted that the draft guideline pointed out the importance of language during consultation with transgender and gender-diverse people, noting that “misuse of language, and particularly deliberate misuse of language associated with the sex assigned at birth (misgendering), may cause profound offence.”

Dr. Kasliwal cited the example of “using the correct pronouns when addressing someone and receiving any information about a person’s gender diversity neutrally and nonjudgementally.”

Edward Morris, MD, president of the Royal College of Obstetricians and Gynaecologists, acknowledged that trans and gender-diverse individuals say they often feel judged and misunderstood by the health service. “This can act as a barrier for them when it comes to accessing vital care, and we as health care professionals have a role to play in making them feel listened to and recognized.”

“This draft guideline is our first attempt to ensure we are providing personalised care for all our patients,” said Dr. Morris. “We welcome feedback on this draft to ensure the guideline is the best as it can be for clinicians and the trans and gender-diverse individuals who use our services.”

The draft guideline as peer-review draft, Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is available on the RCOG website. Consultation is open until Sept. 6, 2022.

A version of this article first appeared on Medscape.com.

Gynecologic and obstetric health care needs of transgender and gender-diverse adults, including fertility preservation, ending masculinizing hormones in pregnancy, and support for “chest-feeding” are proposed in a novel draft guideline issued by the U.K.’s Royal College of Obstetricians and Gynaecologists.

The draft Green-top Guideline on Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is open for consultation and comment until Sept. 6. It aims to address the specific needs of transgender and gender-diverse individuals that, according to the guideline, are currently not consistently included in specialist training programs or in continuing professional development.

With a rise in the number of people seeking to transition, obstetricians and gynecologists are seeing more transgender and gender-diverse patients. Phil Rolland, MD, consultant gynecological oncologist from Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, and member of the guideline committee, said that, “It is highly likely that if an obstetrician or gynaecologist hasn’t already consulted or treated a trans or gender-diverse patient then it is only a matter of time before they do.”

He stressed the importance of ensuring inclusivity in obstetric and gynecologic care. “We know that trans people are more likely to have poor experiences when accessing health care, and we can do better.”

The U.K.-based guideline follows a similar document from the American College of Obstetricians and Gynecologists, put in place in March 2021, as reported by this news organization. It called for greater “awareness, knowledge, and sensitivity” in caring for these patients and noted that “bias from health care professionals leads to inadequate access to, underuse of, and inequities within the health care system for transgender patients.”
 

Guideline addresses fertility preservation, obstetric care, and more

Regarding fertility preservation, discussions around protecting future options should be held before endocrine interventions and/or gender-affirming genital or pelvic surgery procedures, says the guideline. In addition, gynecologic problems that can be experienced need to be explained.

The guideline also addresses obstetric care, advising that trans men on long-acting masculinizing hormone therapy should stop therapy 3 months prior to conception. People who conceive while taking masculinizing hormone therapy should discontinue the therapy as soon as possible.

Birth mode should be discussed with all trans men who plan to conceive, ideally at a prepregnancy counseling appointment, but at minimum, before the third trimester. Choice of feeding manner should also be addressed in the antenatal period, with trans men who wish to chest feed offered chest-feeding support, similar to that given to cis women.

The RCOG guideline comes in the wake of the U.K. government’s new Women’s Health Strategy for England, released in July, which notes that trans men (with female reproductive organs) should be able to access screening services for cervical and breast cancer, a position upheld by the RCOG guideline.

Other key recommendations include that obstetricians and gynecologists, when approached by transgender and gender-diverse people to help with identity-related issues, should liaise with gender-identity specialist services to provide appropriate care.
 

Removing bias, providing affirming care

Asha Kasliwal, MD, consultant in Community Gynaecology and Reproductive Health Care, Manchester, England, and president of the Faculty of Sexual and Reproductive Healthcare, also reflected on how transgender and gender-diverse people often feel uncomfortable accessing care, which could lead to, “many people failing to seek or continue health care because of concerns over how they will be treated,” adding that there were associated reports of poor clinical outcomes.

She highlighted that the draft guideline pointed out the importance of language during consultation with transgender and gender-diverse people, noting that “misuse of language, and particularly deliberate misuse of language associated with the sex assigned at birth (misgendering), may cause profound offence.”

Dr. Kasliwal cited the example of “using the correct pronouns when addressing someone and receiving any information about a person’s gender diversity neutrally and nonjudgementally.”

Edward Morris, MD, president of the Royal College of Obstetricians and Gynaecologists, acknowledged that trans and gender-diverse individuals say they often feel judged and misunderstood by the health service. “This can act as a barrier for them when it comes to accessing vital care, and we as health care professionals have a role to play in making them feel listened to and recognized.”

“This draft guideline is our first attempt to ensure we are providing personalised care for all our patients,” said Dr. Morris. “We welcome feedback on this draft to ensure the guideline is the best as it can be for clinicians and the trans and gender-diverse individuals who use our services.”

The draft guideline as peer-review draft, Care of Trans and Gender Diverse Adults in Obstetrics and Gynaecology is available on the RCOG website. Consultation is open until Sept. 6, 2022.

A version of this article first appeared on Medscape.com.

Bulevirtide (Hepcludex) monotherapy significantly reduces the load of hepatitis delta virus (HDV) and is safe in difficult-to-treat patients with compensated cirrhosis and clinically significant portal hypertension, according to the results of an ongoing 1-year study.

In presenting a poster with these findings at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver, lead author Elisabetta Degasperi, MD, from the Grand Hospital Maggiore Policlinico in Milan, said that they were important “because they confirm the safety of this drug in real life.”

Dr. Degasperi and colleagues showed that bulevirtide leads to a significant viral response in 78% of patients by week 48, which was measured using the outcome of greater than 2 log decline in HDV RNA from baseline.

Dr. Degasperi added that the research still needed to assess the longer-term benefits, but “so far the 1-year results clearly show an initial benefit that is not only a good viral response but also one of disease control and a slight improvement in liver function.”
 

Addressing an immense, unmet therapeutic need

HDV requires the presence of hepatitis B virus to replicate. Bulevirtide blocks the entry of HDV and hepatitis B virus into hepatocytes.

In July 2020, it was conditionally approved in the European Economic Area for use to treat chronic HDV infection in adults with compensated liver disease upon confirmation of HDV RNA in the blood. It currently remains an investigational agent in the United States, as well as outside of the EEA.

The ongoing trial led by Dr. Degasperi is specifically conducted in patients with compensated cirrhosis who also have clinically significant portal hypertension, where safety and efficacy are unknown.

Dr. Degasperi said in an interview that, although HDV was rare, there is nonetheless an “immense” need for effective therapies against it, especially in young patients with advanced liver disease.

“We have a lot of patients with hepatitis D who have not responded to other antiviral treatment. Right now, the only other available treatment is pegylated interferon,” she said. “Unfortunately, rates of sustained viral response to pegylated interferon are extremely low at around 30% of patients.”

Chronic HDV is the most severe form of viral hepatitis and can have mortality rates as high as 50% within 5 years in patients with cirrhosis.

The management of hepatitis D is also complicated by the fact that patients with advanced cirrhosis and clinically significant portal hypertension cannot be treated with pegylated interferon owing to lack of efficacy and safety reasons, including a high risk for decompensation and liver-related complications. Pegylated interferon is contraindicated in these patients.
 

Bulevirtide at 48 weeks: A closer look at the findings

Eighteen patients with HDV, compensated cirrhosis, and clinically significant portal hypertension were consecutively enrolled in this single-center, longitudinal study.

All received bulevirtide monotherapy at 2 mg/day and underwent monitoring every 2 months. They were also treated with nucleotide analogs for their hepatitis B virus, which was suppressed when they began bulevirtide.

Clinical and virologic characteristics were collected at baseline, at weeks 4 and 8, and then every 8 weeks thereafter.

Bulevirtide led to a significant viral response such that by week 48, HDV RNA declined by 3.1 log IU/mL (range, 0.2-4.6 log IU/mL), was undetectable in six patients (33%), and was less than 100 IU/L in 50% of patients. Two patients were nonresponders. In addition, 78% of patients achieved at least an HDV RNA 2 log decline from baseline.

There was also a normalization of biochemical response in the majority of patients.

Alanine aminotransferase normalization was seen in 89% of patients and declined by a median of 34 U/L (range, 15-76 U/L) over 48 weeks. Aspartate aminotransferase declined to 39 U/L (range, 21-92 U/L). A combined response was seen in 72% of patients, reported Dr. Degasperi.

“Previously, we only had results from a phase 2 study, so we had no idea of the results over such a long treatment period,” said Dr. Degasperi. “It is also the first time we have been able to treat these patients with such advanced disease that is so difficult to manage.”

“Real-world results are typically inferior to those from clinical trials, but the viral decline is comparable to phase 2 trials, and the first report of the phase 3 trial,” said Dr. Degasperi.

Gamma-glutamyltransferase, alpha-fetoprotein, immunoglobulin G, and gamma-globulin levels also improved, whereas hepatitis B surface antigen, hepatitis B virus RNA, hepatitis B core-related antigen, platelet, and bilirubin values did not significantly change.

“All patients were Child-Pugh score A, so well-compensated [disease]. However, they increased a little bit in liver function by week 48,” Dr. Degasperi said. “This was important for this very advanced disease population.”

She added that the safety profile was very favorable, with no adverse events, including no injection-site reactions.

There was an asymptomatic increase in serum bile acids. “No patients complained about itching or pruritus,” Dr. Degasperi said.
 

What’s ahead for bulevirtide?

In a comment, Marc Bourlière, MD, from Saint Joseph Hospital in Marseilles, France, welcomed the decrease in viral load.

“This is known to be beneficial in terms of reducing morbidity and mortality in hepatitis D,” he said. “Remember that this disease is very difficult to treat, and until now, we have had no drug available. Pegylated interferon achieves cure in only 30% of patients, and half of these relapse, so actually only 15% have a meaningful response from pegylated interferon.”

“The main issue is its use as a daily subcutaneous injection. In clinical practice, it is a little bit complicated to set up, but once done, it is quite well accepted,” he said.

“I’m impressed with these results to date because there are no other compounds that have, as yet, achieved such results. This is impressive,” he added. “But whether it translates into a long-term response we don’t yet know.”

Dr. Bourlière also noted the meaningful 2-point log decline, noting that “HDV RNA negativity where treatment can be stopped would be really meaningful, but this endpoint is hard to obtain.”

Dr. Bourlière is awaiting results of the current ongoing phase 2/3 study, which would help determine a possible final treatment duration. He is also curious to settle the ongoing debate about whether bulevirtide should be used alone or in combination.

“We need to combine bulevirtide with pegylated interferon in less-advanced patients, because we know it is more potent and active against the HDV RNA,” he said.

Dr. Degasperi has previously declared she was on the advisory board for AbbVie and has spoken and taught for Gilead, MSD, and AbbVie. Dr. Bourlière declared interests with all companies involved in the R&D of liver therapies.

A version of this article first appeared on Medscape.com.

Bulevirtide (Hepcludex) monotherapy significantly reduces the load of hepatitis delta virus (HDV) and is safe in difficult-to-treat patients with compensated cirrhosis and clinically significant portal hypertension, according to the results of an ongoing 1-year study.

In presenting a poster with these findings at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver, lead author Elisabetta Degasperi, MD, from the Grand Hospital Maggiore Policlinico in Milan, said that they were important “because they confirm the safety of this drug in real life.”

Dr. Degasperi and colleagues showed that bulevirtide leads to a significant viral response in 78% of patients by week 48, which was measured using the outcome of greater than 2 log decline in HDV RNA from baseline.

Dr. Degasperi added that the research still needed to assess the longer-term benefits, but “so far the 1-year results clearly show an initial benefit that is not only a good viral response but also one of disease control and a slight improvement in liver function.”
 

Addressing an immense, unmet therapeutic need

HDV requires the presence of hepatitis B virus to replicate. Bulevirtide blocks the entry of HDV and hepatitis B virus into hepatocytes.

In July 2020, it was conditionally approved in the European Economic Area for use to treat chronic HDV infection in adults with compensated liver disease upon confirmation of HDV RNA in the blood. It currently remains an investigational agent in the United States, as well as outside of the EEA.

The ongoing trial led by Dr. Degasperi is specifically conducted in patients with compensated cirrhosis who also have clinically significant portal hypertension, where safety and efficacy are unknown.

Dr. Degasperi said in an interview that, although HDV was rare, there is nonetheless an “immense” need for effective therapies against it, especially in young patients with advanced liver disease.

“We have a lot of patients with hepatitis D who have not responded to other antiviral treatment. Right now, the only other available treatment is pegylated interferon,” she said. “Unfortunately, rates of sustained viral response to pegylated interferon are extremely low at around 30% of patients.”

Chronic HDV is the most severe form of viral hepatitis and can have mortality rates as high as 50% within 5 years in patients with cirrhosis.

The management of hepatitis D is also complicated by the fact that patients with advanced cirrhosis and clinically significant portal hypertension cannot be treated with pegylated interferon owing to lack of efficacy and safety reasons, including a high risk for decompensation and liver-related complications. Pegylated interferon is contraindicated in these patients.
 

Bulevirtide at 48 weeks: A closer look at the findings

Eighteen patients with HDV, compensated cirrhosis, and clinically significant portal hypertension were consecutively enrolled in this single-center, longitudinal study.

All received bulevirtide monotherapy at 2 mg/day and underwent monitoring every 2 months. They were also treated with nucleotide analogs for their hepatitis B virus, which was suppressed when they began bulevirtide.

Clinical and virologic characteristics were collected at baseline, at weeks 4 and 8, and then every 8 weeks thereafter.

Bulevirtide led to a significant viral response such that by week 48, HDV RNA declined by 3.1 log IU/mL (range, 0.2-4.6 log IU/mL), was undetectable in six patients (33%), and was less than 100 IU/L in 50% of patients. Two patients were nonresponders. In addition, 78% of patients achieved at least an HDV RNA 2 log decline from baseline.

There was also a normalization of biochemical response in the majority of patients.

Alanine aminotransferase normalization was seen in 89% of patients and declined by a median of 34 U/L (range, 15-76 U/L) over 48 weeks. Aspartate aminotransferase declined to 39 U/L (range, 21-92 U/L). A combined response was seen in 72% of patients, reported Dr. Degasperi.

“Previously, we only had results from a phase 2 study, so we had no idea of the results over such a long treatment period,” said Dr. Degasperi. “It is also the first time we have been able to treat these patients with such advanced disease that is so difficult to manage.”

“Real-world results are typically inferior to those from clinical trials, but the viral decline is comparable to phase 2 trials, and the first report of the phase 3 trial,” said Dr. Degasperi.

Gamma-glutamyltransferase, alpha-fetoprotein, immunoglobulin G, and gamma-globulin levels also improved, whereas hepatitis B surface antigen, hepatitis B virus RNA, hepatitis B core-related antigen, platelet, and bilirubin values did not significantly change.

“All patients were Child-Pugh score A, so well-compensated [disease]. However, they increased a little bit in liver function by week 48,” Dr. Degasperi said. “This was important for this very advanced disease population.”

She added that the safety profile was very favorable, with no adverse events, including no injection-site reactions.

There was an asymptomatic increase in serum bile acids. “No patients complained about itching or pruritus,” Dr. Degasperi said.
 

What’s ahead for bulevirtide?

In a comment, Marc Bourlière, MD, from Saint Joseph Hospital in Marseilles, France, welcomed the decrease in viral load.

“This is known to be beneficial in terms of reducing morbidity and mortality in hepatitis D,” he said. “Remember that this disease is very difficult to treat, and until now, we have had no drug available. Pegylated interferon achieves cure in only 30% of patients, and half of these relapse, so actually only 15% have a meaningful response from pegylated interferon.”

“The main issue is its use as a daily subcutaneous injection. In clinical practice, it is a little bit complicated to set up, but once done, it is quite well accepted,” he said.

“I’m impressed with these results to date because there are no other compounds that have, as yet, achieved such results. This is impressive,” he added. “But whether it translates into a long-term response we don’t yet know.”

Dr. Bourlière also noted the meaningful 2-point log decline, noting that “HDV RNA negativity where treatment can be stopped would be really meaningful, but this endpoint is hard to obtain.”

Dr. Bourlière is awaiting results of the current ongoing phase 2/3 study, which would help determine a possible final treatment duration. He is also curious to settle the ongoing debate about whether bulevirtide should be used alone or in combination.

“We need to combine bulevirtide with pegylated interferon in less-advanced patients, because we know it is more potent and active against the HDV RNA,” he said.

Dr. Degasperi has previously declared she was on the advisory board for AbbVie and has spoken and taught for Gilead, MSD, and AbbVie. Dr. Bourlière declared interests with all companies involved in the R&D of liver therapies.

A version of this article first appeared on Medscape.com.

Bulevirtide (Hepcludex) monotherapy significantly reduces the load of hepatitis delta virus (HDV) and is safe in difficult-to-treat patients with compensated cirrhosis and clinically significant portal hypertension, according to the results of an ongoing 1-year study.

In presenting a poster with these findings at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver, lead author Elisabetta Degasperi, MD, from the Grand Hospital Maggiore Policlinico in Milan, said that they were important “because they confirm the safety of this drug in real life.”

Dr. Degasperi and colleagues showed that bulevirtide leads to a significant viral response in 78% of patients by week 48, which was measured using the outcome of greater than 2 log decline in HDV RNA from baseline.

Dr. Degasperi added that the research still needed to assess the longer-term benefits, but “so far the 1-year results clearly show an initial benefit that is not only a good viral response but also one of disease control and a slight improvement in liver function.”
 

Addressing an immense, unmet therapeutic need

HDV requires the presence of hepatitis B virus to replicate. Bulevirtide blocks the entry of HDV and hepatitis B virus into hepatocytes.

In July 2020, it was conditionally approved in the European Economic Area for use to treat chronic HDV infection in adults with compensated liver disease upon confirmation of HDV RNA in the blood. It currently remains an investigational agent in the United States, as well as outside of the EEA.

The ongoing trial led by Dr. Degasperi is specifically conducted in patients with compensated cirrhosis who also have clinically significant portal hypertension, where safety and efficacy are unknown.

Dr. Degasperi said in an interview that, although HDV was rare, there is nonetheless an “immense” need for effective therapies against it, especially in young patients with advanced liver disease.

“We have a lot of patients with hepatitis D who have not responded to other antiviral treatment. Right now, the only other available treatment is pegylated interferon,” she said. “Unfortunately, rates of sustained viral response to pegylated interferon are extremely low at around 30% of patients.”

Chronic HDV is the most severe form of viral hepatitis and can have mortality rates as high as 50% within 5 years in patients with cirrhosis.

The management of hepatitis D is also complicated by the fact that patients with advanced cirrhosis and clinically significant portal hypertension cannot be treated with pegylated interferon owing to lack of efficacy and safety reasons, including a high risk for decompensation and liver-related complications. Pegylated interferon is contraindicated in these patients.
 

Bulevirtide at 48 weeks: A closer look at the findings

Eighteen patients with HDV, compensated cirrhosis, and clinically significant portal hypertension were consecutively enrolled in this single-center, longitudinal study.

All received bulevirtide monotherapy at 2 mg/day and underwent monitoring every 2 months. They were also treated with nucleotide analogs for their hepatitis B virus, which was suppressed when they began bulevirtide.

Clinical and virologic characteristics were collected at baseline, at weeks 4 and 8, and then every 8 weeks thereafter.

Bulevirtide led to a significant viral response such that by week 48, HDV RNA declined by 3.1 log IU/mL (range, 0.2-4.6 log IU/mL), was undetectable in six patients (33%), and was less than 100 IU/L in 50% of patients. Two patients were nonresponders. In addition, 78% of patients achieved at least an HDV RNA 2 log decline from baseline.

There was also a normalization of biochemical response in the majority of patients.

Alanine aminotransferase normalization was seen in 89% of patients and declined by a median of 34 U/L (range, 15-76 U/L) over 48 weeks. Aspartate aminotransferase declined to 39 U/L (range, 21-92 U/L). A combined response was seen in 72% of patients, reported Dr. Degasperi.

“Previously, we only had results from a phase 2 study, so we had no idea of the results over such a long treatment period,” said Dr. Degasperi. “It is also the first time we have been able to treat these patients with such advanced disease that is so difficult to manage.”

“Real-world results are typically inferior to those from clinical trials, but the viral decline is comparable to phase 2 trials, and the first report of the phase 3 trial,” said Dr. Degasperi.

Gamma-glutamyltransferase, alpha-fetoprotein, immunoglobulin G, and gamma-globulin levels also improved, whereas hepatitis B surface antigen, hepatitis B virus RNA, hepatitis B core-related antigen, platelet, and bilirubin values did not significantly change.

“All patients were Child-Pugh score A, so well-compensated [disease]. However, they increased a little bit in liver function by week 48,” Dr. Degasperi said. “This was important for this very advanced disease population.”

She added that the safety profile was very favorable, with no adverse events, including no injection-site reactions.

There was an asymptomatic increase in serum bile acids. “No patients complained about itching or pruritus,” Dr. Degasperi said.
 

What’s ahead for bulevirtide?

In a comment, Marc Bourlière, MD, from Saint Joseph Hospital in Marseilles, France, welcomed the decrease in viral load.

“This is known to be beneficial in terms of reducing morbidity and mortality in hepatitis D,” he said. “Remember that this disease is very difficult to treat, and until now, we have had no drug available. Pegylated interferon achieves cure in only 30% of patients, and half of these relapse, so actually only 15% have a meaningful response from pegylated interferon.”

“The main issue is its use as a daily subcutaneous injection. In clinical practice, it is a little bit complicated to set up, but once done, it is quite well accepted,” he said.

“I’m impressed with these results to date because there are no other compounds that have, as yet, achieved such results. This is impressive,” he added. “But whether it translates into a long-term response we don’t yet know.”

Dr. Bourlière also noted the meaningful 2-point log decline, noting that “HDV RNA negativity where treatment can be stopped would be really meaningful, but this endpoint is hard to obtain.”

Dr. Bourlière is awaiting results of the current ongoing phase 2/3 study, which would help determine a possible final treatment duration. He is also curious to settle the ongoing debate about whether bulevirtide should be used alone or in combination.

“We need to combine bulevirtide with pegylated interferon in less-advanced patients, because we know it is more potent and active against the HDV RNA,” he said.

Dr. Degasperi has previously declared she was on the advisory board for AbbVie and has spoken and taught for Gilead, MSD, and AbbVie. Dr. Bourlière declared interests with all companies involved in the R&D of liver therapies.

A version of this article first appeared on Medscape.com.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.