Bianca Nogrady

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

Treatment with etanercept does not appear to achieve significant clinical improvement in patients suspected of having nonradiographic axial spondyloarthritis (nr-axSpA) but without positive MRI signs of sacroiliitis and/or elevated C-reactive protein (CRP) levels, research suggests.

A paper published in Arthritis & Rheumatology presents the outcomes of a randomized, double-blind, placebo-controlled trial of a 16-week course of etanercept at 25 mg twice weekly in 80 tumor necrosis factor inhibitor (TNFi)–naive patients with suspected nr-axSpA. Patients all had chronic inflammatory back pain, at least two spondyloarthritis features – such as HLA-B27 positivity, asymmetrical arthritis, or family history of ankylosing spondylitis – as well as high disease activity and insufficient response to at least two NSAIDs. These patients meet the “clinical arm” of Assessment of SpondyloArthritis international Society (ASAS) criteria for classifying axSpA at an early stage of disease but not “imaging-arm” requirements for the presence of active inflammatory lesions of the sacroiliac joints (SIJ) on MRI and one additional SpA feature.

Whether these imaging criteria and objective evidence of elevated inflammation are necessary to fulfill when considering TNFi treatment for patients with suspected nr-axSpA in daily practice is an important question to address, the authors pointed out, because “in many studies, the presence of a positive MRI-SIJ is one of the prerequisites to start a TNF inhibitor treatment in patients with nr-axSpA.” In addition, starting a TNFi is dependent on failure of at least two NSAIDs and an elevated CRP level when the MRI is negative, which is problematic since in some studies raised CRP levels were found in only 30% of the nr-axSpA patients and 59%-64% of nr-axSpA patients with high disease activity do not have active inflammatory SIJ lesions on MRI. On top of these concerns is the fact that many people who do not have axSpA show false-positive results of bone marrow edema on MRI of the SIJ, such as postpartum women, recreational runners, professional athletes, and army recruits undergoing physical training, they added.

In the current study at the end of the 16-week course of treatment, researchers found no statistically significant difference between the treatment and placebo group in the number of patients who achieved a 20% improvement in ASAS response criteria (16.7% vs. 11.1%; P = .5), nor in those who had at least 40% improvement (8.3% in both groups). This was regardless of sex, age, NSAID or disease-modifying antirheumatic drug use, HLA-B27 status, or other clinical factors.

Similarly, there was no statistically significant difference between the two groups in the number of patients who met response criteria for the Ankylosing Spondylitis Disease Activity Score based on CRP for either clinical improvement or major improvement.

Participants underwent MRI at baseline and at 16 and 24 weeks, which revealed similar numbers of active inflammatory SIJ lesions in each group. The two groups also had similar Spondyloarthritis Research Consortium of Canada scores at baseline and 16 weeks, but a slightly – yet statistically significant – higher score in the etanercept group at 24 weeks.

However, during the first 16 weeks of the study, patients in the etanercept group showed greater improvements in pain and erythrocyte sedimentation rate (ESR), compared with those in the placebo group.

After the 16-week treatment course, participants were followed for another 8 weeks. During this time, participants in the etanercept group showed a worsening in their mean Bath Ankylosing Spondylitis Metrology Index score, CRP level, and ESR, compared with the placebo group.

While the number of participants who experienced an adverse event by 16 weeks was similar in both groups, more patients in the etanercept group experienced an adverse effect likely related to the study drug.

Study results in the context of previous findings

Commenting on their findings, first author Tamara Rusman, of the Amsterdam University Medical Center, and coauthors wrote that the results suggested early treatment with etanercept in patients without a positive MRI and raised CRP levels was not effective.

However, they acknowledged that two previous placebo-controlled studies had specifically included patients with nr-axSpA and found a significantly better treatment response to TNF inhibitors than to placebo. One of these studies included a significant number of patients with MRI-detected active inflammatory SIJ lesions at baseline, which is a known predictor of treatment response.

“The relatively low number of patients with either a positive MRI-SIJ (23%) and/or elevated CRP level (13%) at baseline in our study could be an explanation for the absence of a treatment effect in favor of etanercept,” they wrote.

They also raised the possibility that their choice of study population didn’t truly capture patients with nr-axSpA, and that it was not powered to compare patients with or without a positive MRI or raised CRP level at baseline.

“It would be interesting to know whether our study results will be replicated by others in comparable study populations with equal numbers of patients with and without a positive MRI-SIJ and raised CRP in the future,” they wrote.

The study was supported by an unrestricted financial grant from Pfizer and ReumaNederland. No conflicts of interest were declared.

SOURCE: Rusman T et al. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41607.

Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.

SilverV/Thinkstock

A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.

However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.

“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.

Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.

In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).

The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.

This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.

“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.

When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.

The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.

“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.

More selective expression of IL-23 in synovium

Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.

“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“

Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.

“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.

Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.

“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”

However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.

“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.

The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.

SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.

SilverV/Thinkstock

A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.

However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.

“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.

Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.

In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).

The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.

This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.

“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.

When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.

The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.

“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.

More selective expression of IL-23 in synovium

Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.

“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“

Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.

“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.

Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.

“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”

However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.

“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.

The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.

SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.

SilverV/Thinkstock

A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.

However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.

“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.

Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.

In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).

The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.

This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.

“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.

When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.

The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.

“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.

More selective expression of IL-23 in synovium

Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.

“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“

Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.

“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.

Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.

“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”

However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.

“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.

The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.

SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Machine-based learning of genetic and epigenetic characteristics of patients with rheumatoid arthritis could help to predict who is likely to benefit from the biologic drugs adalimumab and etanercept, according to results from a longitudinal, observational cohort study.

In the study, machine learning models created by researchers from Utrecht University in the Netherlands using different parameters predicted true-positive rates for response to adalimumab ranging from 76% to 90% and true-negative rates ranging from 70% to 89%, while for etanercept true-positive rates ranged from about 60% to 80% and true-negative rates ranged from about 82% to 98%.

“These results suggest that we can accurately predict the clinical response before adalimumab and etanercept treatment using molecular signatures-based machine learning models, although the prediction accuracy of these molecular signatures differs between cell types and treatments, underlining the need to study more than one drug, cell type, or epigenetic layers,” first author Weiyang Tao and colleagues wrote in Arthritis & Rheumatology. The ability to predict which tumor necrosis factor inhibitor (TNFi) is the first choice for treatment would be highly beneficial in reducing the time to effective treatment, which has been extensively proven to be a paramount factor for achieving long-sustained disease remission, they noted.

The researchers analyzed gene expression and epigenetic signatures in 80 patients with rheumatoid arthritis prior to treatment with adalimumab or etanercept and then examined patients’ response to treatment at 6 months. They then used that information to build a machine learning model to try to predict treatment response.

Overall, 47.5% of patients were treated with adalimumab, and 52.5% were treated with etanercept. Among the adalimumab group, 53% had a good or moderate response to treatment at 6 months, and among those treated with etanercept, 45% had a good or moderate response.

While there were no differences in baseline clinical parameters between responders and nonresponders, the study found significant genetic and epigenetic differences between patients.

They identified 549 genes that showed significantly different levels of expression between responders and nonresponders treated with adalimumab – in particular, genes involved in DNA and nucleotide binding – and 460 genes that were differentially expressed between etanercept responders and nonresponders, including genes involved in TNF-receptor signaling. However, only 2% of these differentially expressed genes were common in both the adalimumab and etanercept groups, suggesting treatment responses for these two medications have distinct gene signatures.

Looking at DNA methylation, researchers found 16,141 CpG positions – sites of DNA methylation – that were differentially methylated between adalimumab responders and nonresponders, 46% of which were hypermethylated among responders but not nonresponders. In the etanercept group, there were 17,026 differentially methylated sites in responders and nonresponders, 76.3% of which were hypermethylated among responders.

The researchers also noted that among the adalimumab responders, the hypermethylated sites were more likely to be found in the upstream and promoter regions of genes, and on CpG islands.

“Thus, on epigenetic level, we observed a distinct hypermethylation pattern between adalimumab and etanercept responders, suggesting the role of epigenetics in defining response towards adalimumab and to etanercept in PBMCs [peripheral blood mononuclear cells],” the authors wrote.

Given the differences in gene signatures seen in the adalimumab responders and etanercept responders, researchers speculated that different cell types might be involved in the responses to these two treatments. They undertook RNA sequencing on the variety of immune cell types known to be involved in rheumatoid arthritis, which revealed gene-expression differences between adalimumab responders and nonresponders in their CD4+ T cells but not in monocytes. However, the gene-expression differences between etanercept responders and nonresponders were seen in both CD4+ T cells and monocytes.

The study was supported by AbbVie, which manufactures adalimumab, and two authors were supported by the China Scholarship Council and the Netherlands Organization for Scientific Research. No conflicts of interest were declared.

SOURCE: Tao W et al. Arthritis Rheumatol. 2020 Sep 10. doi: 10.1002/art.41516.

Trabecular bone loss in patients with axial spondyloarthritis is associated with spinal progression in the form of more syndesmophytes, new research suggests.

A paper published in Seminars in Arthritis and Rheumatism reports the outcomes of a prospective observational cohort study in 245 patients with axial spondyloarthritis that sought to identify possible predictors of spinal radiographic progression of the disease.

Joon-Yong Jung, MD, PhD, and colleagues from the Catholic University of Korea, Seoul, South Korea, wrote that inflammation of the vertebrae is the first stage of progression of axial spondyloarthritis. One hypothesis is that this inflammation is associated with trabecular bone loss, which then leads to spinal instability, which in turns causes biomechanical stress on the area and the formation of new bone as syndesmophytes.

To evaluate the possible relationship between trabecular bone loss and syndesmophytes, researchers used dual-energy x-ray absorptiometry imaging of the lumbar spine, which can assess the microarchitecture of trabecular bone, as well as radiographs of the cervical and lumbar spine at 2 and 4 years of follow-up to assess the presence of syndesmophytes.

At baseline, 40% of patients had syndesmophytes, and the mean number of syndesmophytes was 3.3. A total of 11% of patients at baseline had mild trabecular bone loss, defined as trabecular bone score values between 1.230 and 1.310, and 10% had severe trabecular bone loss, with a score of 1.230 or less.

While on average patients had an increase of 1.41 syndesmophytes every 2 years during the study, patients with severe trabecular bone loss at baseline formed 1.26 more syndesmophytes every 2 years than did patients with normal trabecular bone loss score. After adjusting for variables such as disease activity and clinical factors, the authors found that both mild and severe trabecular bone loss were independently associated with progression of structural damage in the cervical and lumbar spine.

Patients with mild trabecular bone loss had a 120% greater odds of new syndesmophyte formation over the next 2 years, compared with those with normal trabecular bone loss scores, while those with severe loss had a 280% greater odds.

“The more severe the trabecular bone loss, the stronger the effect on the progression of the spine,” the authors wrote. Other factors associated with new syndesmophyte formation included higher C-reactive protein levels, longer symptom duration, smoking, and high NSAID index.

The study also pointed to an association between trabecular bone loss and modified Stoke Ankylosing Spondylitis Spinal Score. Patients with severe trabecular bone loss showed an average increase of 0.37 in their modified Stoke Ankylosing Spondylitis Spinal Score over 2 years, compared with patients with normal trabecular bone loss score at baseline, even after adjusting for confounders.

The authors commented that inflammation is hypothesized to lead to structural damage in two ways. “Inflammation-induced bone loss in the spine results in instability, another type of biomechanical stress, which then triggers a biomechanical response in an attempt to increase stability,” they wrote. Or inflammation leads to the formation of granulated repair tissue which then triggers new bone formation.

Whatever the mechanism, the authors said finding that trabecular bone loss is associated with disease progression suggests a possible use for the trabecular bone score as a practical and noninvasive means to predict spinal progression in patients with axial spondyloarthritis.

The study received no funding, and the authors said they had no conflicts of interest to declare.

SOURCE: Jung J-Y et al. Semin Arthritis Rheum. 2020;50(5):827-33.

Trabecular bone loss in patients with axial spondyloarthritis is associated with spinal progression in the form of more syndesmophytes, new research suggests.

A paper published in Seminars in Arthritis and Rheumatism reports the outcomes of a prospective observational cohort study in 245 patients with axial spondyloarthritis that sought to identify possible predictors of spinal radiographic progression of the disease.

Joon-Yong Jung, MD, PhD, and colleagues from the Catholic University of Korea, Seoul, South Korea, wrote that inflammation of the vertebrae is the first stage of progression of axial spondyloarthritis. One hypothesis is that this inflammation is associated with trabecular bone loss, which then leads to spinal instability, which in turns causes biomechanical stress on the area and the formation of new bone as syndesmophytes.

To evaluate the possible relationship between trabecular bone loss and syndesmophytes, researchers used dual-energy x-ray absorptiometry imaging of the lumbar spine, which can assess the microarchitecture of trabecular bone, as well as radiographs of the cervical and lumbar spine at 2 and 4 years of follow-up to assess the presence of syndesmophytes.

At baseline, 40% of patients had syndesmophytes, and the mean number of syndesmophytes was 3.3. A total of 11% of patients at baseline had mild trabecular bone loss, defined as trabecular bone score values between 1.230 and 1.310, and 10% had severe trabecular bone loss, with a score of 1.230 or less.

While on average patients had an increase of 1.41 syndesmophytes every 2 years during the study, patients with severe trabecular bone loss at baseline formed 1.26 more syndesmophytes every 2 years than did patients with normal trabecular bone loss score. After adjusting for variables such as disease activity and clinical factors, the authors found that both mild and severe trabecular bone loss were independently associated with progression of structural damage in the cervical and lumbar spine.

Patients with mild trabecular bone loss had a 120% greater odds of new syndesmophyte formation over the next 2 years, compared with those with normal trabecular bone loss scores, while those with severe loss had a 280% greater odds.

“The more severe the trabecular bone loss, the stronger the effect on the progression of the spine,” the authors wrote. Other factors associated with new syndesmophyte formation included higher C-reactive protein levels, longer symptom duration, smoking, and high NSAID index.

The study also pointed to an association between trabecular bone loss and modified Stoke Ankylosing Spondylitis Spinal Score. Patients with severe trabecular bone loss showed an average increase of 0.37 in their modified Stoke Ankylosing Spondylitis Spinal Score over 2 years, compared with patients with normal trabecular bone loss score at baseline, even after adjusting for confounders.

The authors commented that inflammation is hypothesized to lead to structural damage in two ways. “Inflammation-induced bone loss in the spine results in instability, another type of biomechanical stress, which then triggers a biomechanical response in an attempt to increase stability,” they wrote. Or inflammation leads to the formation of granulated repair tissue which then triggers new bone formation.

Whatever the mechanism, the authors said finding that trabecular bone loss is associated with disease progression suggests a possible use for the trabecular bone score as a practical and noninvasive means to predict spinal progression in patients with axial spondyloarthritis.

The study received no funding, and the authors said they had no conflicts of interest to declare.

SOURCE: Jung J-Y et al. Semin Arthritis Rheum. 2020;50(5):827-33.

Trabecular bone loss in patients with axial spondyloarthritis is associated with spinal progression in the form of more syndesmophytes, new research suggests.

A paper published in Seminars in Arthritis and Rheumatism reports the outcomes of a prospective observational cohort study in 245 patients with axial spondyloarthritis that sought to identify possible predictors of spinal radiographic progression of the disease.

Joon-Yong Jung, MD, PhD, and colleagues from the Catholic University of Korea, Seoul, South Korea, wrote that inflammation of the vertebrae is the first stage of progression of axial spondyloarthritis. One hypothesis is that this inflammation is associated with trabecular bone loss, which then leads to spinal instability, which in turns causes biomechanical stress on the area and the formation of new bone as syndesmophytes.

To evaluate the possible relationship between trabecular bone loss and syndesmophytes, researchers used dual-energy x-ray absorptiometry imaging of the lumbar spine, which can assess the microarchitecture of trabecular bone, as well as radiographs of the cervical and lumbar spine at 2 and 4 years of follow-up to assess the presence of syndesmophytes.

At baseline, 40% of patients had syndesmophytes, and the mean number of syndesmophytes was 3.3. A total of 11% of patients at baseline had mild trabecular bone loss, defined as trabecular bone score values between 1.230 and 1.310, and 10% had severe trabecular bone loss, with a score of 1.230 or less.

While on average patients had an increase of 1.41 syndesmophytes every 2 years during the study, patients with severe trabecular bone loss at baseline formed 1.26 more syndesmophytes every 2 years than did patients with normal trabecular bone loss score. After adjusting for variables such as disease activity and clinical factors, the authors found that both mild and severe trabecular bone loss were independently associated with progression of structural damage in the cervical and lumbar spine.

Patients with mild trabecular bone loss had a 120% greater odds of new syndesmophyte formation over the next 2 years, compared with those with normal trabecular bone loss scores, while those with severe loss had a 280% greater odds.

“The more severe the trabecular bone loss, the stronger the effect on the progression of the spine,” the authors wrote. Other factors associated with new syndesmophyte formation included higher C-reactive protein levels, longer symptom duration, smoking, and high NSAID index.

The study also pointed to an association between trabecular bone loss and modified Stoke Ankylosing Spondylitis Spinal Score. Patients with severe trabecular bone loss showed an average increase of 0.37 in their modified Stoke Ankylosing Spondylitis Spinal Score over 2 years, compared with patients with normal trabecular bone loss score at baseline, even after adjusting for confounders.

The authors commented that inflammation is hypothesized to lead to structural damage in two ways. “Inflammation-induced bone loss in the spine results in instability, another type of biomechanical stress, which then triggers a biomechanical response in an attempt to increase stability,” they wrote. Or inflammation leads to the formation of granulated repair tissue which then triggers new bone formation.

Whatever the mechanism, the authors said finding that trabecular bone loss is associated with disease progression suggests a possible use for the trabecular bone score as a practical and noninvasive means to predict spinal progression in patients with axial spondyloarthritis.

The study received no funding, and the authors said they had no conflicts of interest to declare.

SOURCE: Jung J-Y et al. Semin Arthritis Rheum. 2020;50(5):827-33.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.

A school curriculum–based intervention aimed at reducing the stigma of mental illness was associated with a nearly fourfold increase in the likelihood of youth with significant symptoms seeking treatment.

Ridofranz/Getty Images

Writing in Pediatrics, researchers reported the outcome of a 2-year, longitudinal, cluster-randomized trial involving 416 students in sixth-grade classes in 14 schools across Texas.

The intervention was a school-based curriculum program called Eliminating the Stigma of Differences (ESD); a 3-hour, three-module curriculum program delivered over 1 week, which contained a mix of teaching, group discussion, and homework exercises.

One module explored the idea of difference; the definition, causes and consequences of stigma; ways to end stigma; and the description, causes and treatments of mental illness as well as the barriers to seeking help. The other two modules explored specific mental illnesses in more detail but with content designed to stimulate empathy.

The study compared this with two other interventions – in-class presentations and discussions led by two young adults with a history of mental illness; or exposure to anti-stigma printed materials – and a no-intervention control.

The study found that involvement with the curriculum program was associated with a significant and sustained increase in knowledge of and attitudes to mental illness compared with the control and other interventions, and with significant decreases in social distance, which measures the extent to which children are unwilling to interact with someone who is identified as having a mental illness. This association was seen even after the researchers controlled for other factors such as a participants’ knowledge of or attitudes toward mental illness before the intervention, their age, sex, race or ethnicity, or their parents’ educational level.

“Our study, in combination with other studies, suggests strongly that youth can be positively influenced at a relatively young age, fostering changes in mental health attitudes and behaviors that last, as our study has shown, for at least 2 years,” wrote Bruce G. Link, PhD, of the School of Public Policy at the University of California, Riverside, and coauthors.

The study also found that among youth who were experiencing a high level of symptoms of mental illness, the curriculum-based intervention was associated with nearly fourfold higher odds of seeking treatment (odd ratio 3.9, P < .05), after adjustment for similar covariates.

The authors looked separately at whether this self-reported treatment-seeking was the first time that students had sought treatment, a continuation of treatment seeking, or a return to it. All three showed similar odds ratios but small sample sizes meant they did not reach statistical significance.

“We do know that negative attitudes toward mental illnesses and the exceptionally large percentage of people who experience but do not receive treatment for such illnesses are problems that have been with us for a long time,” Dr. Link and associates said. “Interventions such as ESD represent a partial but positive response to this public mental health challenge.”

The intervention didn’t lead to a significant increase in treatment-seeking behavior among students with low levels of mental illness symptoms.

There were no significant differences in the effectiveness of the intervention across race or ethnicity, sex, education level of caregivers, or the baseline attitudes toward mental illness. The only exception was seen with Latino youth, where the intervention was not associated with a decrease in social distancing.

Contact intervention, in which two young people with a history of mental illness came to talk to classes and participate in discussions, was not associated with any significant changes in attitudes.

“A potential explanation is that contact is not as effective in youth, a possibility that is supported by a meta-analysis showing diminished effects of contact compared with educational interventions in adolescents,” Dr. Link and associates said.

In an accompanying editorial, Nathaniel Beers, MD, of Children’s National Hospital in Washington, and Dr. Shashank V. Joshi, MD, of Stanford (Calif.) University, wrote that more than one-fifth of children and youth in the United States are diagnosed with behavioral health needs before they reach the age of 18, but the perception of stigma can make families reluctant to access treatment.

“Previous research has highlighted the importance of stigma reduction in school-based settings as a crucial component in changing the social norms about seeking help among diverse youth populations,” they said. Reducing stigma also can reduce detrimental outcomes from social isolation and bullying.

Dr. Beers and Dr. Joshi noted that school-based interventions can have a substantial and lasting effect, with the benefit of influencing parents and staff in addition to students.

“Combined with screening and improved access to school-based mental health services, this curriculum could add a critical component to addressing the mental health needs of children and youth in the United States,” they concluded.

The study was supported by the National Institute of Mental Health and National Institutes of Health. The authors said they had no relevant financial disclosures. Dr. Beers and Dr. Joshi received no external funding, and they said they had no relevant financial disclosures.

SOURCES: Link B. et al. Pediatrics 2020, May 20. doi: 10.1542/peds.2019-0780; Beers N and Joshi SV. Pediatrics. 2020, May 20. doi: 10.1542/peds.2020-0127.

A school curriculum–based intervention aimed at reducing the stigma of mental illness was associated with a nearly fourfold increase in the likelihood of youth with significant symptoms seeking treatment.

Ridofranz/Getty Images

Writing in Pediatrics, researchers reported the outcome of a 2-year, longitudinal, cluster-randomized trial involving 416 students in sixth-grade classes in 14 schools across Texas.

The intervention was a school-based curriculum program called Eliminating the Stigma of Differences (ESD); a 3-hour, three-module curriculum program delivered over 1 week, which contained a mix of teaching, group discussion, and homework exercises.

One module explored the idea of difference; the definition, causes and consequences of stigma; ways to end stigma; and the description, causes and treatments of mental illness as well as the barriers to seeking help. The other two modules explored specific mental illnesses in more detail but with content designed to stimulate empathy.

The study compared this with two other interventions – in-class presentations and discussions led by two young adults with a history of mental illness; or exposure to anti-stigma printed materials – and a no-intervention control.

The study found that involvement with the curriculum program was associated with a significant and sustained increase in knowledge of and attitudes to mental illness compared with the control and other interventions, and with significant decreases in social distance, which measures the extent to which children are unwilling to interact with someone who is identified as having a mental illness. This association was seen even after the researchers controlled for other factors such as a participants’ knowledge of or attitudes toward mental illness before the intervention, their age, sex, race or ethnicity, or their parents’ educational level.

“Our study, in combination with other studies, suggests strongly that youth can be positively influenced at a relatively young age, fostering changes in mental health attitudes and behaviors that last, as our study has shown, for at least 2 years,” wrote Bruce G. Link, PhD, of the School of Public Policy at the University of California, Riverside, and coauthors.

The study also found that among youth who were experiencing a high level of symptoms of mental illness, the curriculum-based intervention was associated with nearly fourfold higher odds of seeking treatment (odd ratio 3.9, P < .05), after adjustment for similar covariates.

The authors looked separately at whether this self-reported treatment-seeking was the first time that students had sought treatment, a continuation of treatment seeking, or a return to it. All three showed similar odds ratios but small sample sizes meant they did not reach statistical significance.

“We do know that negative attitudes toward mental illnesses and the exceptionally large percentage of people who experience but do not receive treatment for such illnesses are problems that have been with us for a long time,” Dr. Link and associates said. “Interventions such as ESD represent a partial but positive response to this public mental health challenge.”

The intervention didn’t lead to a significant increase in treatment-seeking behavior among students with low levels of mental illness symptoms.

There were no significant differences in the effectiveness of the intervention across race or ethnicity, sex, education level of caregivers, or the baseline attitudes toward mental illness. The only exception was seen with Latino youth, where the intervention was not associated with a decrease in social distancing.

Contact intervention, in which two young people with a history of mental illness came to talk to classes and participate in discussions, was not associated with any significant changes in attitudes.

“A potential explanation is that contact is not as effective in youth, a possibility that is supported by a meta-analysis showing diminished effects of contact compared with educational interventions in adolescents,” Dr. Link and associates said.

In an accompanying editorial, Nathaniel Beers, MD, of Children’s National Hospital in Washington, and Dr. Shashank V. Joshi, MD, of Stanford (Calif.) University, wrote that more than one-fifth of children and youth in the United States are diagnosed with behavioral health needs before they reach the age of 18, but the perception of stigma can make families reluctant to access treatment.

“Previous research has highlighted the importance of stigma reduction in school-based settings as a crucial component in changing the social norms about seeking help among diverse youth populations,” they said. Reducing stigma also can reduce detrimental outcomes from social isolation and bullying.

Dr. Beers and Dr. Joshi noted that school-based interventions can have a substantial and lasting effect, with the benefit of influencing parents and staff in addition to students.

“Combined with screening and improved access to school-based mental health services, this curriculum could add a critical component to addressing the mental health needs of children and youth in the United States,” they concluded.

The study was supported by the National Institute of Mental Health and National Institutes of Health. The authors said they had no relevant financial disclosures. Dr. Beers and Dr. Joshi received no external funding, and they said they had no relevant financial disclosures.

SOURCES: Link B. et al. Pediatrics 2020, May 20. doi: 10.1542/peds.2019-0780; Beers N and Joshi SV. Pediatrics. 2020, May 20. doi: 10.1542/peds.2020-0127.

A school curriculum–based intervention aimed at reducing the stigma of mental illness was associated with a nearly fourfold increase in the likelihood of youth with significant symptoms seeking treatment.

Ridofranz/Getty Images

Writing in Pediatrics, researchers reported the outcome of a 2-year, longitudinal, cluster-randomized trial involving 416 students in sixth-grade classes in 14 schools across Texas.

The intervention was a school-based curriculum program called Eliminating the Stigma of Differences (ESD); a 3-hour, three-module curriculum program delivered over 1 week, which contained a mix of teaching, group discussion, and homework exercises.

One module explored the idea of difference; the definition, causes and consequences of stigma; ways to end stigma; and the description, causes and treatments of mental illness as well as the barriers to seeking help. The other two modules explored specific mental illnesses in more detail but with content designed to stimulate empathy.

The study compared this with two other interventions – in-class presentations and discussions led by two young adults with a history of mental illness; or exposure to anti-stigma printed materials – and a no-intervention control.

The study found that involvement with the curriculum program was associated with a significant and sustained increase in knowledge of and attitudes to mental illness compared with the control and other interventions, and with significant decreases in social distance, which measures the extent to which children are unwilling to interact with someone who is identified as having a mental illness. This association was seen even after the researchers controlled for other factors such as a participants’ knowledge of or attitudes toward mental illness before the intervention, their age, sex, race or ethnicity, or their parents’ educational level.

“Our study, in combination with other studies, suggests strongly that youth can be positively influenced at a relatively young age, fostering changes in mental health attitudes and behaviors that last, as our study has shown, for at least 2 years,” wrote Bruce G. Link, PhD, of the School of Public Policy at the University of California, Riverside, and coauthors.

The study also found that among youth who were experiencing a high level of symptoms of mental illness, the curriculum-based intervention was associated with nearly fourfold higher odds of seeking treatment (odd ratio 3.9, P < .05), after adjustment for similar covariates.

The authors looked separately at whether this self-reported treatment-seeking was the first time that students had sought treatment, a continuation of treatment seeking, or a return to it. All three showed similar odds ratios but small sample sizes meant they did not reach statistical significance.

“We do know that negative attitudes toward mental illnesses and the exceptionally large percentage of people who experience but do not receive treatment for such illnesses are problems that have been with us for a long time,” Dr. Link and associates said. “Interventions such as ESD represent a partial but positive response to this public mental health challenge.”

The intervention didn’t lead to a significant increase in treatment-seeking behavior among students with low levels of mental illness symptoms.

There were no significant differences in the effectiveness of the intervention across race or ethnicity, sex, education level of caregivers, or the baseline attitudes toward mental illness. The only exception was seen with Latino youth, where the intervention was not associated with a decrease in social distancing.

Contact intervention, in which two young people with a history of mental illness came to talk to classes and participate in discussions, was not associated with any significant changes in attitudes.

“A potential explanation is that contact is not as effective in youth, a possibility that is supported by a meta-analysis showing diminished effects of contact compared with educational interventions in adolescents,” Dr. Link and associates said.

In an accompanying editorial, Nathaniel Beers, MD, of Children’s National Hospital in Washington, and Dr. Shashank V. Joshi, MD, of Stanford (Calif.) University, wrote that more than one-fifth of children and youth in the United States are diagnosed with behavioral health needs before they reach the age of 18, but the perception of stigma can make families reluctant to access treatment.

“Previous research has highlighted the importance of stigma reduction in school-based settings as a crucial component in changing the social norms about seeking help among diverse youth populations,” they said. Reducing stigma also can reduce detrimental outcomes from social isolation and bullying.

Dr. Beers and Dr. Joshi noted that school-based interventions can have a substantial and lasting effect, with the benefit of influencing parents and staff in addition to students.

“Combined with screening and improved access to school-based mental health services, this curriculum could add a critical component to addressing the mental health needs of children and youth in the United States,” they concluded.

The study was supported by the National Institute of Mental Health and National Institutes of Health. The authors said they had no relevant financial disclosures. Dr. Beers and Dr. Joshi received no external funding, and they said they had no relevant financial disclosures.

SOURCES: Link B. et al. Pediatrics 2020, May 20. doi: 10.1542/peds.2019-0780; Beers N and Joshi SV. Pediatrics. 2020, May 20. doi: 10.1542/peds.2020-0127.

A second booster dose of the influenza vaccine in vaccine-naive children may significantly reduce their likelihood of getting the disease, new research suggests.

KatarzynaBialasiewicz/Thinkstock

Writing for JAMA Pediatrics, researchers reported on a case-control study of 7,533 children presenting to outpatient clinics – all in the U.S. Influenza Vaccine Effectiveness Network – with acute respiratory tract illnesses from 2014 to 2018. The study looked at the effectiveness of vaccination against laboratory-confirmed influenza.

Current U.S. guidelines recommend that children aged 6 months to 8 years receive two doses of the influenza vaccine initially – a priming dose and a booster dose – while those aged 9 years or older are considered to be ‘immunologically primed’ and therefore only require one annual dose.

The study found that 60% of the children had received two doses of the influenza vaccine during their first vaccination season, and 68% were first vaccinated before the current influenza season. Of those who had been vaccinated, 89% had received their first influenza vaccine dose when they were younger than 2 years.

Among the 2,140 children who were unvaccinated before the current influenza season, the 436 children who received two doses of the influenza vaccine had 43% lower odds of influenza compared with the 466 children who received one dose. The overall vaccine effectiveness among this vaccine-naive group aged under 2 years was 38%; for those who received two doses it was 53%, and for those who received one dose it was 23%.

“The higher risk of infection resulting from underdeveloped immune and respiratory tract systems provides a reason to identify vaccination strategies focusing on this vulnerable population of younger children,” wrote Jessie R. Chung, MPH, of the Influenza Division of the Centers for Disease Control and Prevention, and coauthors. “Promoting efforts to improve influenza vaccine coverage—particularly with 2 doses in the first vaccination season – may reduce the burden of influenza illness among young children, who are particularly vulnerable to complications and death from influenza infection.”

Overall 52% of children were unvaccinated for the current influenza season and 9% were partially vaccinated. Of those who were fully vaccinated for the current season, 83% had received one dose in the current season, and 17% had received two doses.

The authors found that full vaccination against any influenza was associated with a 22% lower odds of influenza compared with partial vaccination (95% confidence interval, 0.61-1.01), with partial vaccination defined as anything less than two doses of vaccine in the current season – at least 4 weeks apart – or two or more doses before the current season and one or more doses in the current season. However, even children who were only partially vaccinated still showed statistically significant vaccine effectiveness, except for those who received one dose of vaccine in the current season and were aged under 2 years.

“Compared with older children, young children, even if healthy, are at an elevated risk of influenza infection and influenza-associated complications, such as hospitalization,” the authors wrote. “One recent simulation study reported that even small improvements in either vaccine coverage or VE [vaccine effectiveness], and ideally both, may avert substantial amounts of influenza-associated illnesses, medical visits, and hospitalizations.”

The study also noted that children who had received only a single previous vaccine dose rarely received two doses in the current season.

In an accompanying editorial, Claire Abraham, MD, and Melissa S. Stockwell, MD, of Columbia University Medical Center, New York, wrote that modeling suggested that in the 2017-2018 influenza season, vaccination prevented 1.3 million cases of infection, 895,000 medical visits, 10,500 hospitalizations and 111 deaths in children aged under 5 years.

“This study highlights the importance of administering 2 doses of the influenza vaccine to children younger than 9 years for whom 2 doses are needed, and especially to vaccine naive children younger than 2 years,” they wrote.

But despite many studies showing the impact and importance of influenza vaccination, uptake of this vaccine remained lower than for other pediatric vaccines.

“This present study reemphasizes the need for further research exploring why families who are seemingly willing to vaccinate their children against influenza, as indicated by their receiving the first needed dose of influenza vaccine, find barriers to receiving all of the needed doses, placing their children at higher risk for contracting a potentially devastating virus.”

The U.S. Influenza Vaccine Effectiveness Network is funded by the CDC, and this project also received support from the National Institutes of Health. Eight authors declared grants from the CDC during the conduct of the study, and five declared grants and other funding from private industry outside the study.

SOURCE: Chung J et al. JAMA Pediatrics 2020 May 4. doi: 10.1001/jamapediatrics.2020.0372.

A second booster dose of the influenza vaccine in vaccine-naive children may significantly reduce their likelihood of getting the disease, new research suggests.

KatarzynaBialasiewicz/Thinkstock

Writing for JAMA Pediatrics, researchers reported on a case-control study of 7,533 children presenting to outpatient clinics – all in the U.S. Influenza Vaccine Effectiveness Network – with acute respiratory tract illnesses from 2014 to 2018. The study looked at the effectiveness of vaccination against laboratory-confirmed influenza.

Current U.S. guidelines recommend that children aged 6 months to 8 years receive two doses of the influenza vaccine initially – a priming dose and a booster dose – while those aged 9 years or older are considered to be ‘immunologically primed’ and therefore only require one annual dose.

The study found that 60% of the children had received two doses of the influenza vaccine during their first vaccination season, and 68% were first vaccinated before the current influenza season. Of those who had been vaccinated, 89% had received their first influenza vaccine dose when they were younger than 2 years.

Among the 2,140 children who were unvaccinated before the current influenza season, the 436 children who received two doses of the influenza vaccine had 43% lower odds of influenza compared with the 466 children who received one dose. The overall vaccine effectiveness among this vaccine-naive group aged under 2 years was 38%; for those who received two doses it was 53%, and for those who received one dose it was 23%.

“The higher risk of infection resulting from underdeveloped immune and respiratory tract systems provides a reason to identify vaccination strategies focusing on this vulnerable population of younger children,” wrote Jessie R. Chung, MPH, of the Influenza Division of the Centers for Disease Control and Prevention, and coauthors. “Promoting efforts to improve influenza vaccine coverage—particularly with 2 doses in the first vaccination season – may reduce the burden of influenza illness among young children, who are particularly vulnerable to complications and death from influenza infection.”

Overall 52% of children were unvaccinated for the current influenza season and 9% were partially vaccinated. Of those who were fully vaccinated for the current season, 83% had received one dose in the current season, and 17% had received two doses.

The authors found that full vaccination against any influenza was associated with a 22% lower odds of influenza compared with partial vaccination (95% confidence interval, 0.61-1.01), with partial vaccination defined as anything less than two doses of vaccine in the current season – at least 4 weeks apart – or two or more doses before the current season and one or more doses in the current season. However, even children who were only partially vaccinated still showed statistically significant vaccine effectiveness, except for those who received one dose of vaccine in the current season and were aged under 2 years.

“Compared with older children, young children, even if healthy, are at an elevated risk of influenza infection and influenza-associated complications, such as hospitalization,” the authors wrote. “One recent simulation study reported that even small improvements in either vaccine coverage or VE [vaccine effectiveness], and ideally both, may avert substantial amounts of influenza-associated illnesses, medical visits, and hospitalizations.”

The study also noted that children who had received only a single previous vaccine dose rarely received two doses in the current season.

In an accompanying editorial, Claire Abraham, MD, and Melissa S. Stockwell, MD, of Columbia University Medical Center, New York, wrote that modeling suggested that in the 2017-2018 influenza season, vaccination prevented 1.3 million cases of infection, 895,000 medical visits, 10,500 hospitalizations and 111 deaths in children aged under 5 years.

“This study highlights the importance of administering 2 doses of the influenza vaccine to children younger than 9 years for whom 2 doses are needed, and especially to vaccine naive children younger than 2 years,” they wrote.

But despite many studies showing the impact and importance of influenza vaccination, uptake of this vaccine remained lower than for other pediatric vaccines.

“This present study reemphasizes the need for further research exploring why families who are seemingly willing to vaccinate their children against influenza, as indicated by their receiving the first needed dose of influenza vaccine, find barriers to receiving all of the needed doses, placing their children at higher risk for contracting a potentially devastating virus.”

The U.S. Influenza Vaccine Effectiveness Network is funded by the CDC, and this project also received support from the National Institutes of Health. Eight authors declared grants from the CDC during the conduct of the study, and five declared grants and other funding from private industry outside the study.

SOURCE: Chung J et al. JAMA Pediatrics 2020 May 4. doi: 10.1001/jamapediatrics.2020.0372.

A second booster dose of the influenza vaccine in vaccine-naive children may significantly reduce their likelihood of getting the disease, new research suggests.

KatarzynaBialasiewicz/Thinkstock

Writing for JAMA Pediatrics, researchers reported on a case-control study of 7,533 children presenting to outpatient clinics – all in the U.S. Influenza Vaccine Effectiveness Network – with acute respiratory tract illnesses from 2014 to 2018. The study looked at the effectiveness of vaccination against laboratory-confirmed influenza.

Current U.S. guidelines recommend that children aged 6 months to 8 years receive two doses of the influenza vaccine initially – a priming dose and a booster dose – while those aged 9 years or older are considered to be ‘immunologically primed’ and therefore only require one annual dose.

The study found that 60% of the children had received two doses of the influenza vaccine during their first vaccination season, and 68% were first vaccinated before the current influenza season. Of those who had been vaccinated, 89% had received their first influenza vaccine dose when they were younger than 2 years.

Among the 2,140 children who were unvaccinated before the current influenza season, the 436 children who received two doses of the influenza vaccine had 43% lower odds of influenza compared with the 466 children who received one dose. The overall vaccine effectiveness among this vaccine-naive group aged under 2 years was 38%; for those who received two doses it was 53%, and for those who received one dose it was 23%.

“The higher risk of infection resulting from underdeveloped immune and respiratory tract systems provides a reason to identify vaccination strategies focusing on this vulnerable population of younger children,” wrote Jessie R. Chung, MPH, of the Influenza Division of the Centers for Disease Control and Prevention, and coauthors. “Promoting efforts to improve influenza vaccine coverage—particularly with 2 doses in the first vaccination season – may reduce the burden of influenza illness among young children, who are particularly vulnerable to complications and death from influenza infection.”

Overall 52% of children were unvaccinated for the current influenza season and 9% were partially vaccinated. Of those who were fully vaccinated for the current season, 83% had received one dose in the current season, and 17% had received two doses.

The authors found that full vaccination against any influenza was associated with a 22% lower odds of influenza compared with partial vaccination (95% confidence interval, 0.61-1.01), with partial vaccination defined as anything less than two doses of vaccine in the current season – at least 4 weeks apart – or two or more doses before the current season and one or more doses in the current season. However, even children who were only partially vaccinated still showed statistically significant vaccine effectiveness, except for those who received one dose of vaccine in the current season and were aged under 2 years.

“Compared with older children, young children, even if healthy, are at an elevated risk of influenza infection and influenza-associated complications, such as hospitalization,” the authors wrote. “One recent simulation study reported that even small improvements in either vaccine coverage or VE [vaccine effectiveness], and ideally both, may avert substantial amounts of influenza-associated illnesses, medical visits, and hospitalizations.”

The study also noted that children who had received only a single previous vaccine dose rarely received two doses in the current season.

In an accompanying editorial, Claire Abraham, MD, and Melissa S. Stockwell, MD, of Columbia University Medical Center, New York, wrote that modeling suggested that in the 2017-2018 influenza season, vaccination prevented 1.3 million cases of infection, 895,000 medical visits, 10,500 hospitalizations and 111 deaths in children aged under 5 years.

“This study highlights the importance of administering 2 doses of the influenza vaccine to children younger than 9 years for whom 2 doses are needed, and especially to vaccine naive children younger than 2 years,” they wrote.

But despite many studies showing the impact and importance of influenza vaccination, uptake of this vaccine remained lower than for other pediatric vaccines.

“This present study reemphasizes the need for further research exploring why families who are seemingly willing to vaccinate their children against influenza, as indicated by their receiving the first needed dose of influenza vaccine, find barriers to receiving all of the needed doses, placing their children at higher risk for contracting a potentially devastating virus.”

The U.S. Influenza Vaccine Effectiveness Network is funded by the CDC, and this project also received support from the National Institutes of Health. Eight authors declared grants from the CDC during the conduct of the study, and five declared grants and other funding from private industry outside the study.

SOURCE: Chung J et al. JAMA Pediatrics 2020 May 4. doi: 10.1001/jamapediatrics.2020.0372.

Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.

Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.

“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”

The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.

The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.

“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.

The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.

Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.

“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.

“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.

The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.

SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5

Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.

Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.

“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”

The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.

The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.

“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.

The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.

Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.

“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.

“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.

The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.

SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5

Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.

Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.

“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”

The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.

The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.

“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.

The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.

Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.

“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.

“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.

The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.

SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5

Microdiscectomy could significantly reduce pain intensity at 6 months in people with chronic sciatica caused by lumbar disc herniation, a randomized controlled trial has found.

Catherine Yeulet/Thinkstock

Researchers reported the outcomes of a single-center trial in the New England Journal of Medicine in which 128 patients with chronic sciatica resulting from lumbar disc herniation were randomized either to microdiscectomy or 6 months of standardized nonoperative care, followed by surgery if required.

Chris S. Bailey, MD, of the Schulich School of Medicine and Dentistry at Western University in Toronto, Ontario, and coauthors wrote that, while the majority of patients with sciatica from acute herniation of the lumbar disc improve with conservative care, there is little study comparing surgery with conservative care in patients whose symptoms have lasted longer than 3 months.

In this study, all patients had experienced unilateral radiculopathy for 4-12 months. Those randomized to surgery were operated on a median of 3.1 weeks after enrollment, while those randomized to nonsurgical treatment received education on exercise, functioning, and the use of oral analgesics, as well as active physiotherapy and epidural glucocorticoid injections if needed.

At 6 months, the surgical group showed significantly lower visual analog scale scores for leg-pain intensity, compared with the nonsurgical group (2.8 vs. 5.2; 95% confidence interval, 1.4-3.4; P < .001) and the difference persisted at 1 year (2.6 vs. 4.7).

In an editorial accompanying the study, Andrew J. Schoenfeld, MD, and James D. Kang, MD, of the department of orthopedic surgery at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, described the results in this group of patients with persistent sciatica as “encouraging,” and suggested the improvement may be because the surgery achieves more rapid decompression of the compressed nerve.

“Patients in the current trial who were assigned to undergo surgery received the intervention relatively quickly, at a median of 3 weeks, and it is reasonable to conclude that expeditious removal of the nerve compression minimized the potential for long-term persistence of pain,” they wrote.

Among the 64 patients who were randomized to nonsurgical treatment, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment in the study. These patients tended to be younger at baseline, and less likely to have an asymmetrical decrease in reflexes.

The intention-to-treat analysis found a similar rate of surgical adverse events in the group initially randomized to surgery and the group who crossed over to have surgery (6% vs. 8%). Two patients in the surgical group and one in the crossover group experienced superficial wound infections, while two patients in the crossover group and one in the surgical group experienced new-onset postoperative neuropathic pain. Two patients in the surgical group also had a recurrence of their herniation; one underwent further surgery for it 250 days after the initial procedure, and the other did not.

The secondary outcomes of the study were disability score, physical health, mental health, back pain intensity, satisfaction with treatment, and employment status. All these showed differences that favored the surgical intervention, but “the absence of a prespecified plan for adjustment for multiple comparisons does not allow for clinical inferences from secondary outcomes.”

The authors noted that some previous randomized trials have shown that surgery was better than conservative care among patients with lumbar disc herniation for the first 6 months, but those trials largely focused on patients who had had symptoms for less than 4 months at the time of the intervention. The results of these trials had also been mixed; some trials in patients with shorter duration of symptoms found little or no benefit of surgery over conservative care.

“The decision about whether to recommend discectomy or nonsurgical treatment in this population is controversial because a longer duration of symptoms has been correlated with a poorer outcome associated with lumbar discectomy in some studies,” they wrote. “However, patients may prefer to avoid surgery if they think that nonsurgical treatment could be successful or if they anticipate a risk from surgery.”

There was the risk for selection bias in the study, the authors said, because both surgeons and patients might have been less inclined to go with nonsurgical care in cases of more severe sciatic pain. However they said patients did not have the option of choosing to have surgery at the center outside the trial, which should have minimized that risk.

The authors of the editorial noted that while the study limited itself to patients who had had symptoms for 4-12 months, it didn’t account for other clinical factors that might impact the outcome of discectomy, such as the size of disc herniation or extent of nerve compression.

They also pointed out that questions still remained about which patients were more likely to benefit from immediate surgical intervention and how long nonsurgical care should be trialed before recommending surgery.

The study was supported by a grant from the Physicians’ Services Incorporated Foundation. None of the study authors reported conflicts of interest. Dr. Kang reported grants from Pfizer, personal fees from DePuy (Johnson & Johnson), nonfinancial support from Stryker, owning stock in ALung and Cardiorobotics, and serving on a scientific advisory board for OnPoint Surgical, outside the submitted work. Dr. Schoenfeld reported grants from the National Institute for Arthritis and Musculoskeletal and Skin Diseases, the Orthopaedic Research and Education Foundation, and the U.S. Department of Defense, outside the submitted work.

SOURCE: Bailey C et al. N Engl J Med. 2020;382:1093-102.

Microdiscectomy could significantly reduce pain intensity at 6 months in people with chronic sciatica caused by lumbar disc herniation, a randomized controlled trial has found.

Catherine Yeulet/Thinkstock

Researchers reported the outcomes of a single-center trial in the New England Journal of Medicine in which 128 patients with chronic sciatica resulting from lumbar disc herniation were randomized either to microdiscectomy or 6 months of standardized nonoperative care, followed by surgery if required.

Chris S. Bailey, MD, of the Schulich School of Medicine and Dentistry at Western University in Toronto, Ontario, and coauthors wrote that, while the majority of patients with sciatica from acute herniation of the lumbar disc improve with conservative care, there is little study comparing surgery with conservative care in patients whose symptoms have lasted longer than 3 months.

In this study, all patients had experienced unilateral radiculopathy for 4-12 months. Those randomized to surgery were operated on a median of 3.1 weeks after enrollment, while those randomized to nonsurgical treatment received education on exercise, functioning, and the use of oral analgesics, as well as active physiotherapy and epidural glucocorticoid injections if needed.

At 6 months, the surgical group showed significantly lower visual analog scale scores for leg-pain intensity, compared with the nonsurgical group (2.8 vs. 5.2; 95% confidence interval, 1.4-3.4; P < .001) and the difference persisted at 1 year (2.6 vs. 4.7).

In an editorial accompanying the study, Andrew J. Schoenfeld, MD, and James D. Kang, MD, of the department of orthopedic surgery at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, described the results in this group of patients with persistent sciatica as “encouraging,” and suggested the improvement may be because the surgery achieves more rapid decompression of the compressed nerve.

“Patients in the current trial who were assigned to undergo surgery received the intervention relatively quickly, at a median of 3 weeks, and it is reasonable to conclude that expeditious removal of the nerve compression minimized the potential for long-term persistence of pain,” they wrote.

Among the 64 patients who were randomized to nonsurgical treatment, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment in the study. These patients tended to be younger at baseline, and less likely to have an asymmetrical decrease in reflexes.

The intention-to-treat analysis found a similar rate of surgical adverse events in the group initially randomized to surgery and the group who crossed over to have surgery (6% vs. 8%). Two patients in the surgical group and one in the crossover group experienced superficial wound infections, while two patients in the crossover group and one in the surgical group experienced new-onset postoperative neuropathic pain. Two patients in the surgical group also had a recurrence of their herniation; one underwent further surgery for it 250 days after the initial procedure, and the other did not.

The secondary outcomes of the study were disability score, physical health, mental health, back pain intensity, satisfaction with treatment, and employment status. All these showed differences that favored the surgical intervention, but “the absence of a prespecified plan for adjustment for multiple comparisons does not allow for clinical inferences from secondary outcomes.”

The authors noted that some previous randomized trials have shown that surgery was better than conservative care among patients with lumbar disc herniation for the first 6 months, but those trials largely focused on patients who had had symptoms for less than 4 months at the time of the intervention. The results of these trials had also been mixed; some trials in patients with shorter duration of symptoms found little or no benefit of surgery over conservative care.

“The decision about whether to recommend discectomy or nonsurgical treatment in this population is controversial because a longer duration of symptoms has been correlated with a poorer outcome associated with lumbar discectomy in some studies,” they wrote. “However, patients may prefer to avoid surgery if they think that nonsurgical treatment could be successful or if they anticipate a risk from surgery.”

There was the risk for selection bias in the study, the authors said, because both surgeons and patients might have been less inclined to go with nonsurgical care in cases of more severe sciatic pain. However they said patients did not have the option of choosing to have surgery at the center outside the trial, which should have minimized that risk.

The authors of the editorial noted that while the study limited itself to patients who had had symptoms for 4-12 months, it didn’t account for other clinical factors that might impact the outcome of discectomy, such as the size of disc herniation or extent of nerve compression.

They also pointed out that questions still remained about which patients were more likely to benefit from immediate surgical intervention and how long nonsurgical care should be trialed before recommending surgery.

The study was supported by a grant from the Physicians’ Services Incorporated Foundation. None of the study authors reported conflicts of interest. Dr. Kang reported grants from Pfizer, personal fees from DePuy (Johnson & Johnson), nonfinancial support from Stryker, owning stock in ALung and Cardiorobotics, and serving on a scientific advisory board for OnPoint Surgical, outside the submitted work. Dr. Schoenfeld reported grants from the National Institute for Arthritis and Musculoskeletal and Skin Diseases, the Orthopaedic Research and Education Foundation, and the U.S. Department of Defense, outside the submitted work.

SOURCE: Bailey C et al. N Engl J Med. 2020;382:1093-102.

Microdiscectomy could significantly reduce pain intensity at 6 months in people with chronic sciatica caused by lumbar disc herniation, a randomized controlled trial has found.

Catherine Yeulet/Thinkstock

Researchers reported the outcomes of a single-center trial in the New England Journal of Medicine in which 128 patients with chronic sciatica resulting from lumbar disc herniation were randomized either to microdiscectomy or 6 months of standardized nonoperative care, followed by surgery if required.

Chris S. Bailey, MD, of the Schulich School of Medicine and Dentistry at Western University in Toronto, Ontario, and coauthors wrote that, while the majority of patients with sciatica from acute herniation of the lumbar disc improve with conservative care, there is little study comparing surgery with conservative care in patients whose symptoms have lasted longer than 3 months.

In this study, all patients had experienced unilateral radiculopathy for 4-12 months. Those randomized to surgery were operated on a median of 3.1 weeks after enrollment, while those randomized to nonsurgical treatment received education on exercise, functioning, and the use of oral analgesics, as well as active physiotherapy and epidural glucocorticoid injections if needed.

At 6 months, the surgical group showed significantly lower visual analog scale scores for leg-pain intensity, compared with the nonsurgical group (2.8 vs. 5.2; 95% confidence interval, 1.4-3.4; P < .001) and the difference persisted at 1 year (2.6 vs. 4.7).

In an editorial accompanying the study, Andrew J. Schoenfeld, MD, and James D. Kang, MD, of the department of orthopedic surgery at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, described the results in this group of patients with persistent sciatica as “encouraging,” and suggested the improvement may be because the surgery achieves more rapid decompression of the compressed nerve.

“Patients in the current trial who were assigned to undergo surgery received the intervention relatively quickly, at a median of 3 weeks, and it is reasonable to conclude that expeditious removal of the nerve compression minimized the potential for long-term persistence of pain,” they wrote.

Among the 64 patients who were randomized to nonsurgical treatment, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment in the study. These patients tended to be younger at baseline, and less likely to have an asymmetrical decrease in reflexes.

The intention-to-treat analysis found a similar rate of surgical adverse events in the group initially randomized to surgery and the group who crossed over to have surgery (6% vs. 8%). Two patients in the surgical group and one in the crossover group experienced superficial wound infections, while two patients in the crossover group and one in the surgical group experienced new-onset postoperative neuropathic pain. Two patients in the surgical group also had a recurrence of their herniation; one underwent further surgery for it 250 days after the initial procedure, and the other did not.

The secondary outcomes of the study were disability score, physical health, mental health, back pain intensity, satisfaction with treatment, and employment status. All these showed differences that favored the surgical intervention, but “the absence of a prespecified plan for adjustment for multiple comparisons does not allow for clinical inferences from secondary outcomes.”

The authors noted that some previous randomized trials have shown that surgery was better than conservative care among patients with lumbar disc herniation for the first 6 months, but those trials largely focused on patients who had had symptoms for less than 4 months at the time of the intervention. The results of these trials had also been mixed; some trials in patients with shorter duration of symptoms found little or no benefit of surgery over conservative care.

“The decision about whether to recommend discectomy or nonsurgical treatment in this population is controversial because a longer duration of symptoms has been correlated with a poorer outcome associated with lumbar discectomy in some studies,” they wrote. “However, patients may prefer to avoid surgery if they think that nonsurgical treatment could be successful or if they anticipate a risk from surgery.”

There was the risk for selection bias in the study, the authors said, because both surgeons and patients might have been less inclined to go with nonsurgical care in cases of more severe sciatic pain. However they said patients did not have the option of choosing to have surgery at the center outside the trial, which should have minimized that risk.

The authors of the editorial noted that while the study limited itself to patients who had had symptoms for 4-12 months, it didn’t account for other clinical factors that might impact the outcome of discectomy, such as the size of disc herniation or extent of nerve compression.

They also pointed out that questions still remained about which patients were more likely to benefit from immediate surgical intervention and how long nonsurgical care should be trialed before recommending surgery.

The study was supported by a grant from the Physicians’ Services Incorporated Foundation. None of the study authors reported conflicts of interest. Dr. Kang reported grants from Pfizer, personal fees from DePuy (Johnson & Johnson), nonfinancial support from Stryker, owning stock in ALung and Cardiorobotics, and serving on a scientific advisory board for OnPoint Surgical, outside the submitted work. Dr. Schoenfeld reported grants from the National Institute for Arthritis and Musculoskeletal and Skin Diseases, the Orthopaedic Research and Education Foundation, and the U.S. Department of Defense, outside the submitted work.

SOURCE: Bailey C et al. N Engl J Med. 2020;382:1093-102.