Rheumatology News

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

No statistical significance but a numerical difference found

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

No statistical significance but a numerical difference found

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

No statistical significance but a numerical difference found

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

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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


 

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

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

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

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

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

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

Early response seen regardless of previous TNF inhibitor experience

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

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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


 

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

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

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

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

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

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

Early response seen regardless of previous TNF inhibitor experience

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

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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


 

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

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

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

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

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

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

Early response seen regardless of previous TNF inhibitor experience

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

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

Next step: Test in an unselected population

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

Next step: Test in an unselected population

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

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

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

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

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

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

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

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

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

Becky McCall/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

Next step: Test in an unselected population

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

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

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

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

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

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

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

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.

This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.

Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.

The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.

According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.

“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.

When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.

“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.

“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.

Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.

“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.

The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Good news for pregnant women; bad news for fish

As soon as women find out they’re pregnant, doctors recommend they give up smoking, drinking, and eating certain types of fish. That last item may need to be reconsidered, since a recent study supports the idea that it doesn’t matter what type of fish pregnant women are eating, as long as they’re eating it.

franckreporter/Getty Images

Researchers collected data from two different studies that reviewed the mercury levels of mothers from Bristol, England, and the Seychelles, a island chain off East Africa where “fish consumption is high and prenatal mercury levels are 10 times higher than in the [United States],” they said in NeuroToxicology.

Those data showed that the mercury levels had no adverse effects on child development as long as the mother ate fish. The nutrients and vitamins in the fish – vitamin D, long-chain fatty acids, selenium, and iodine – provide protection against mercury. There’s also the already-known benefits to eyesight and intellectual abilities that have been associated with fish consumption.

This analysis goes starkly against the grain of what is commonly recommended to expectant mothers, which is to cut out fish altogether. The researchers suggested that governments should review and change those recommendations to focus on the benefits instead.

As long as women follow the researchers’ recommendation to eat “at least two portions of fish a week, one of which should be oily,” they may not have to lay off on the sushi after all.
 

We’ll show our gut worms the world

Never let it be said that mankind is not a generous species. Sure, we could maybe be kinder to our fellow human beings, maybe declare a little less war on each other, but for the past 50,000 years, we’ve been giving a free ride to millions upon millions to one of mankind’s closest companions: the whipworm.

oksmith/openclipart.org

This revelation into human kindness comes from Denmark, where researchers from Copenhagen conducted a genetic analysis of ancient preserved whipworm eggs found in old Viking and Norse settlements, some of which date back over 2,000 years. In normal conditions genetic material wouldn’t last very long, but these were Viking whipworms eggs with tiny little horned helmets, so the DNA within has remained unchanged. Or it may be the tough chitinous exterior of the eggs protecting the DNA from degrading, combined with their preservation in moist soil.

Once they had their Viking whipworm DNA, the researchers compared it with whipworm DNA from all over the world, tracing its history as it followed mankind from Africa. And it’s been a while: We brought whipworms with us during our initial migration into Asia and Europe over 50,000 years ago. When the Bering land bridge opened up and humanity moved into the Americas, the worms came as well.

This is all possible because the whipworm goes about its parasitic business quietly and cleverly. It mostly sits harmlessly in our digestive systems, producing thousands of eggs a day that get expelled through poop and picked up by another host (human or otherwise); whipworms only cause disease in those with compromised immune systems.

The researchers noted that their study, the first complete genetic analysis of the whipworm, could help combat the parasite, which to this day infects hundred of millions who don’t have access to modern medicine or sanitary conditions. Hopefully, though, the days of free rides will soon be over for the whipworm. After all, if we have to pay hundreds or thousands of dollars to visit other countries, it’s only fair that our parasites do as well.
 

From zero to vasectomy in 6.7 seconds

There’s an old saying that you’ve probably heard: When life gives you lemons, make lemonade. It’s meant to encourage optimism in the face of adversity. Then there’s the new saying we just made up: When life gives you a power outage, plug your surgical instruments into an electric pickup.

Rivian

That’s what Dr. Christopher Yang did, and now we’re making the urologist from Austin, Tex., famous by sharing his surgical/electrical adventure with all 17 of LOTME’s regular readers. That’s some serious lemonade.

Dr. Yang’s tale begins when the electricity went out at his clinic, seemingly forcing him to cancel or reschedule several surgical procedures. Not so fast. Dr. Yang happens to own a Rivian R1T, an electric pickup truck that has four power outlets. A staff member suggested plugging the surgical instruments into the truck and, surprisingly, one of the day’s patients agreed to go ahead with his vasectomy.

“We were fortunate that my normal parking spot is close enough to a patient room to run an extension cord,” Dr. Yang said on TheDrive.com. That extension cord was attached to an electrocautery device, with a handheld device available as backup, and “after we were done, I told his family. We all had a good laugh together too,” Dr. Yang told radio station WGLT in Normal, Ill.

To us, anyway, this opens up all sorts of alternative energy possibilities. Can a windmill power a liposuction? Is a gerbil running in a wheel enough to do a colonoscopy? How many potatoes do you need to keep an EHR going?
 

Learning through random acts of not-exactly noisiness

First things first. Transcranial random noise stimulation (tRNS) is not really noise in the auditory sense of the word. For some people with learning disabilities, though, it can actually be very helpful. The technology, which uses electrodes attached to the head so a weak current can pass through specific parts of the brain, may help those with learning disabilities, perhaps even those with brain injuries and visual deficits, learn, said Dr. Onno van der Groen of Edith Cowan University in Perth, Australia.

littlehenrabi/Getty Images

“When you add this type of stimulation during learning, you get better performance, faster learning and better attention afterwards as well,” he said in a statement from the university.

The researchers say that tRNS can allow the brain to form new connections and pathways, which in turn help a person learn more effectively. “If you do 10 sessions of a visual perception task with the tRNS and then come back and do it again without it, you’ll find you perform better than the control group who hasn’t used it,” Dr. van der Groen noted.

Can this also work for the average person? It’s possible, but tRNS didn’t seem to improve the math skills of a top-level mathematician who underwent the process, according to a case study that Dr. van der Groen mentioned.

This line of work is still pretty new, though, so researchers don’t have all the answers yet. As always, we’re rooting for you, science!

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The U.S. Food and Drug Administration has approved the biologic agent spesolimab (Spevigo) for the treatment of flares in adults with generalized pustular psoriasis (GPP), the company that manufactures the drug has announced.

Until this approval, “there were no FDA-approved options to treat patients experiencing a GPP flare,” Mark Lebwohl, MD, principal investigator in the pivotal spesolimab trial, told this news organization. The approval “is a turning point for dermatologists and clinicians who treat patients living with this devastating and debilitating disease,” he said. Treatment with spesolimab “rapidly improves the clinical symptoms of GPP flares and will greatly improve our ability to help our patients manage painful flares,” noted Dr. Lebwohl, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Spesolimab, manufactured by Boehringer Ingelheim, is a novel, selective monoclonal antibody that blocks interleukin-36 signaling known to be involved in GPP. It received priority review and had orphan drug and breakthrough therapy designation.

GPP affects an estimated 1 of every 10,000 people in the United States.

Though rare, GPP is a potentially life-threatening disease that is distinct from plaque psoriasis. GPP is caused by the accumulation of neutrophils in the skin. Throughout the course of the disease, patients may suffer recurring episodes of widespread eruptions of painful, sterile pustules across all parts of the body.

Spesolimab was evaluated in a global, 12-week, placebo-controlled clinical trial that involved 53 adults experiencing a GPP flare. After 1 week, significantly more patients treated with spesolimab than placebo showed no visible pustules (54% vs 6%), according to the company.

The most common adverse reactions, seen in at least 5% of patients treated with spesolimab, were asthenia and fatigue; nausea and vomiting; headache; pruritus and prurigo; hematoma and bruising at the infusion site; and urinary tract infection.

Dr. Lebwohl is a paid consultant to Boehringer Ingelheim.

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

This article was updated 9/6/22.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

The kids aren’t alright (at identifying fake news online)

If there’s one thing today’s teenagers are good at, it’s the Internet. What with their TokTiks, Fortnights, and memes whose lifespans are measured in milliseconds, it’s only natural that a contingent of people who have never known a world where the Internet wasn’t omnipresent would be highly skilled at navigating the dense, labyrinthine virtual world and the many falsehoods contained within.

Ladies and gentlemen, we’ve been duped, bamboozled, and smeckledorfed. New research from Slovakia suggests the opposite, in fact: Teenagers are just as bad as the rest of us, if not worse, at distinguishing between fake and real online health messaging.

monkeybusinessimages/iStock/Getty Images Plus

For the study, 300 teenagers aged 16-19 years old were shown a group of messages about the health-promoting effects of fruits and vegetables; these messages were either false, true and neutral, or true with some sort of editing (a clickbait title or grammar mistakes) to mask their trustworthiness. Just under half of the subjects identified and trusted the true neutral messages over fake messages, while 41% couldn’t tell the difference and 11% trusted the fake messages more. In addition, they couldn’t tell the difference between fake and true messages when the content seemed plausible.

In a bit of good news, teenagers were just as likely to trust the edited true messages as the true neutral ones, except in instances when the edited message had a clickbait title. They were much less likely to trust those.

Based on their subjects’ rather poor performance, the study authors suggested teenagers go through health literacy and media literacy training, as well as develop their analytical and scientific reasoning. The LOTME staff rather suspects the study authors have never met a teenager. The only thing teenagers are going to get out of health literacy training is fodder for memes to put up on Myspace. Myspace is still a thing, right? We’re not old, we swear.
 

Can a computer help deliver babies?

Delivering babies can be a complicated business. Most doctors and midwives rely on their years of experience and training to make certain decisions for mothers in labor, but an artificial intelligence (AI) algorithm could make the entire process easier and safer.

©Paul Hakimata/thinkstockphotos.com

Researchers from the Mayo Clinic recently reported that using an AI to analyze women’s labor patterns was very successful in determining whether a vaginal or cesarean delivery was appropriate.

They examined over 700 factors and over 66,000 deliveries from the National Institute of Child Health and Human Development’s multicenter Consortium on Safe Labor database to produce a risk-prediction model that may “provide an alternative to conventional labor charts and promote individualization of clinical decisions using baseline and labor characteristics of each patient,” they said in a written statement from the clinic.

It is hoped that the AI will reduce the risk of possible complications and the costs associated with maternal mortality. The AI also could be a significant tool for doctors and midwives in rural areas to determine when a patient needs to be moved to a location with a higher level of care.

“We believe the algorithm will work in real time, meaning every input of new data during an expectant woman’s labor automatically recalculates the risk of adverse outcome,” said senior author Abimbola Famuyide, MD, of the Mayo Clinic.

If it all works out, many lives and dollars could be saved, thanks to science.
 

Democracy, meet COVID-19

Everywhere you look, it seems, someone is trying to keep someone else from doing something: Don’t carry a gun. Don’t get an abortion. Don’t drive so fast. Don’t inhale that whipped cream. Don’t get a vaccine. Don’t put that in your mouth.

One of the biggies these days is voting rights. Some people are trying to prevent other people from voting. But why? Well, turns out that turnout can be bad for your health … at least during a worldwide pandemic event.

mohamed mahmoud hassan

The evidence for that claim comes from researchers who examined the Italian national constitutional referendum conducted in September 2020 along with elections for assembly representatives in 7 of the country’s 20 regions and for mayors in about 12% of municipalities. The combination mattered: Voter turnout was higher in the municipalities that voted for both the referendum and local elections (69%), compared with municipalities voting only for the referendum (47%), the investigators reported in the Journal of Economic Behavior & Organization.

Also occurring in September of 2020 was, as we mentioned, a worldwide pandemic event. You may have heard about it.

The investigators considered the differences in election turnout between the various municipalities and compared them with new weekly COVID-19 infections at the municipality level. “Our model shows that something as fundamental as casting a vote can come at a cost,” investigator Giuseppe Moscelli, PhD, of the University of Surrey (England) said in a written statement.

What was the cost? Each 1% increase in turnout, they found, amounted to an average 1.1% increase in COVID infections after the elections.

See? More people voting means more COVID, which is bad. Which brings us to today’s lesson in people preventing other people from doing something. Don’t let COVID win. Stay in your house and never come out. And get that smeckledorf out of your mouth. You don’t know where it’s been.

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.