Latest News

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

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

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

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

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

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

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

Podcasts, websites, and large “Parenting” sections in bookstores testify to the large demand for parent guidance and support, but also to the fact that there is no one universally accepted guidebook, such as Benjamin Spock provided for parents almost 80 years ago with Baby and Child Care. The Positive Parenting Program — “Triple P” — is a curriculum for parents that focuses on five areas of parental competence and can be applied at different levels of intensity to address different needs, from preventing common problems and promoting healthy development to addressing substantial child behavioral problems.

We will describe the basic components of this curriculum so that you may determine whether it might be useful to the families in your practice. Then we will expand upon the domains that have proven essential for parents to nurture healthy development in their children. Even if you do not have the time or resources to provide the full Triple P curriculum, you can offer these principles directly to parents and decide when to refer them to access more formal parent training and coaching.

Triple P was developed by psychologist Matthew Sanders, to “promote positive, caring relationships between parents and their children and to help parents develop effective management strategies for dealing with a variety of childhood behavior problems and common developmental issues” as his doctoral project in Australia in the 1980s. Research in the 1990s suggested substantial efficacy, and it was packaged for broader adoption in the early 2000s. It is a tiered approach, meaning there is content for universal education (level 1), up through more intensive, specialized, and individualized content to be delivered in group or individual settings focused on building specific skills or addressing select problems. It was originally developed for the parents of 0- to 11-year-old children, with additional curricula for parents of teenagers created later. It always is delivered to parents only, through a mix of video and reading, or in-person groups or individual coaching. While the universal education resources are available for free to families of children under 12 in Australia, resources and training are available for a fee in the United states (triplep.net). Research has demonstrated considerable efficacy at reducing some of the common behavioral problems of childhood, improving parental confidence and family harmony, and decreasing rates of parental depression. It has even demonstrated efficacy in reducing the incidence of child maltreatment.

• 1. Creating a safe and engaging environment for children
• 2. Providing a positive learning environment for children
• 3. Assertive discipline
• 4. Having realistic expectations
• 5. Parental self-care.

The educational materials and more intensive parent trainings are all focused on developing knowledge and skills in the parents that will promote a positive relationship with their children, teach the children new skills while encouraging desirable behaviors, and managing problematic behaviors. The training happens with written or video scenarios, up through individualized skill coaching with homework and direct feedback from trained clinicians. While information about the universally helpful knowledge and skills can be found online or accessed through some local programs in the United States, the higher levels of intervention are less consistently available. You should explore what is available in your community, but even if you don’t have the resources for your own training, you are already offering parent guidance at every visit.

Practical Strategies

Below are practical strategies to offer parents the knowledge and support that are essential to “positive parenting,” so they may nurture their children’s healthiest development.

Attunement: Attunement is simply a parent’s ability to know who their child is and where their child is at any given time. This covers an appreciation of the child’s temperament, style, interests, strengths, and vulnerabilities. Where their child is at includes being able to read that particular child’s cues: Are they hungry? Sleepy? Sick? Frustrated? Parents are the experts on their children, but their children are also always changing. You can help the parents in your practice be intentional about being attuned to their children, so they can always be deepening their understanding of who their children are (becoming) and where they are at in any given moment. This requires protecting regular, unstructured time when they can give their children their full attention: reading, doing an art project, practicing music, or basketball. Schedules are often packed with work and school, driving between many structured activities. Reassure the parents in your practice that time spent in play is just as important. When a parent is present, attentive, and curious, asking questions, learning about the child’s thoughts, feelings and ideas, they are doing some of the most essential (and delightful) work of raising children.

Positive Environment: A “positive environment” is child-centered, with access to age-appropriate activities of a wide range. Offering first-time parents written resources about child development and age-appropriate games, books, and activities is an easy way to support positive parenting. A positive environment also has structure and routines, so children can play and explore with the comfort of knowing what to expect and what is expected of them. Do they have a regular bedtime and bedtime routines? Do they consistently eat dinner together and clean up as a family? Do they have reliable unstructured time together, maybe playing board games or kickball after dinner? These varying but predictable routines provide opportunities for children to practice helping, following through, sharing, and tolerating frustration or failure, and they give parents low-stakes opportunities to offer praise for their effort, compassion when they struggle, and affection for no reason at all. They lower the chances of parent-child interactions being predominantly reactive, demanding, pleading, or angry.

Effective Discipline: A positive environment includes reasonable and consistent consequences for rule breaking and poor behavior, and an essential part of predictability includes clear ground rules for what is expected of children at home, around chores, getting ready for school and bedtime, and their behavior. Parents need to agree on and children should understand what the consequences will be for breaking rules. Parents should also have a clear strategy for consistently and calmly enforcing rules. This is not easy, but is just as important as affection and play. If parents are struggling with discipline, it is worth asking for a specific example to learn about where the trouble lies. Are parents not on the same page? Are they worried about their children’s distress? Do they lose their temper and the matter escalates? Clear ground rules and a game plan can help them to stay calm instead of resorting to pleading and yelling. Speaking with them about the value of planning and communicating about these expectations and rules during a quiet time, not in the midst of conflict, might be enough to help them with effective discipline. Others may need more support. Books like 123 Magic with more detail on how to manage time outs can be helpful. For those parents who are managing greater difficulty, a referral to parent coaching (with a modality such as Triple P, Parent-Child Interaction Training or Collaborative Problem Solving) may be needed.

Parental Well-Being: Being aligned with one’s spouse (or other caregiver) in how to manage challenging child behaviors is essential to a healthy relationship, and overall well-being is an essential ingredient in creating a nurturing, positive environment at home. How is the parents’ communication with each other overall? Do they have time together that is not focused on the children? Does each parent have time for outside interests or hobbies? How about other important relationships? Do they prioritize their own sleep, regular exercise, and good nutrition? It can be powerful if they plan family activities that are centered on their own passions and interests as well as their children’s. It is powerful for parents to hear from you that when they protect some of their time and energy to simply care for their own health and well-being, they are building a positive environment for their children, both in how they will show up for their family and in what they model.
 

Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Suggested Reading

Sanders MR et al. The Development and Dissemination of the Triple P – Positive Parenting Program: A Multilevel Evidence-Based System of Parenting and Family Support. Prev Sci. 2002 Sep;3(3):173-89. doi: 10.1023/a:1019942516231.

Sanders MR. The Triple P System of Evidence-Based Parenting Support: Past, Present, and Future Directions. Clin Child Fam Psychol Rev. 2023 Dec;26(4):880-903. doi: 10.1007/s10567-023-00441-8.

TOPLINE:

Patients with late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with late-onset axial spondyloarthritis (axSpA) are less likely to be positive for human leukocyte antigen B27 (HLA-B27) and have a family history of SpA; they are more likely to present with peripheral arthritis.

METHODOLOGY:

• Researchers conducted a multicenter cross-sectional study including 2165 patients with a clinical diagnosis of axSpA who were identified from the Rheumatic Diseases Portuguese Register from June 2008 to December 2022.
• Patients with symptom onset at or after 45 years of age were referred as late-onset axSpA, whereas those with symptom onset before 45 years as early-onset axSpA.
• Overall, 273 had a diagnosis of late-onset axSpA (mean age at symptom onset, 51.4 years; 55% men) and 1892 had a diagnosis of early-onset axSpA (mean age at symptom onset, 28.9 years; 56% men).
• Independent associations between demographic, clinical, imaging, and treatment characteristics and late-onset axSpA were tested using multivariable logistic regression models.

TAKEAWAY:

• Patients with late-onset axSpA were less likely to be positive for HLA-B27 (51% vs 65%; P < .001) and to have a family history of SpA (8% vs 14%; P < .01), have inflammatory back pain (81% vs 88%; P < .01), and have acute anterior uveitis (13% vs 20%; P < .01) than those with early-onset axSpA.
• Patients with late-onset axSpA had a higher likelihood of having peripheral arthritis than those with early-onset axSpA (36% vs 28%; P < .05).
• The odds of having late-onset axSpA were lower in patients with HLA-B27 positivity (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.7), a family history of SpA (aOR, 0.6; 95% CI, 0.4-0.9), inflammatory back pain (aOR, 0.5; 95% CI, 0.4-0.8), and acute anterior uveitis (aOR, 0.6; 95% CI, 0.4-0.9).
• Conversely, patients with peripheral arthritis had a higher likelihood of developing late-onset axSpA (aOR, 1.5; 95% CI, 1.1-1.9).

IN PRACTICE:

“In this study, we found that [late-onset axSpA] may represent a distinct phenotype with a weaker association with HLA-B27,” the authors wrote. “Whether [late-onset axSpA] comprises a subset of axSpA with a (possibly) different genetic or epigenetic background or rather translates difficulties in recognizing a less typical disease presentation and a population without a genetic marker which can make the diagnostic process more challenging merits further investigation.”

SOURCE:

The study was led by Margarida Lucas Rocha, MD, Department of Rheumatology, ULSA, Faro, Portugal. It was published online in Joint Bone Spine.

LIMITATIONS:

No limitations were reported in the study.

DISCLOSURES:

No relevant funding information and conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.

For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.

Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.

After a little over 2 years I’d had enough and went solo.

I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.

I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.

I can spend more time with the patients who need it. Isn’t that part of why I’m here?

Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).

It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.

The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.

I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.

There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)

But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.

At the end of the day I can tell the guy in the mirror that I’m doing my best.

Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.

In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.

Small practice isn’t for the faint of heart. I freely admit that it’s not for everyone.

But I wish more people would see it as a realistic option, and take the road less traveled.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.

For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.

Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.

After a little over 2 years I’d had enough and went solo.

I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.

I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.

I can spend more time with the patients who need it. Isn’t that part of why I’m here?

Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).

It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.

The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.

I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.

There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)

But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.

At the end of the day I can tell the guy in the mirror that I’m doing my best.

Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.

In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.

Small practice isn’t for the faint of heart. I freely admit that it’s not for everyone.

But I wish more people would see it as a realistic option, and take the road less traveled.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

STAT News recently ran a series on UnitedHealthcare (UHC) and its growing physician empire. This includes the corporation pressuring its employed physicians to see more patients, work weekends, upcode visits, add in diagnoses that will increase reimbursement, yadda, yadda, yadda.

For legal disclaimer purposes, I’m not saying UHC did any of this, nor am I saying they didn’t. But the series on STAT is worth reading.

Reading the articles brings back memories of the last time I was an employed physician, 24 years ago. I didn’t have people telling me to upcode visits, but I do remember hearing terms such as “dollars per physician per square foot” bandied about concerning my performance. At least back then no one was going to yell at me about a 1-star online review from a disgruntled patient.

After a little over 2 years I’d had enough and went solo.

I have no desire at this point to go back to that. I certainly make a lot less money than my employed counterparts, but I also have time and a degree of peace, which are worth something.

I’m not paying for anyone else’s overhead. I don’t slack off, but at least I know what I’m working for, and where the money is going when I write out a check. I can work my schedule around having to take my dog to the vet, or pick a kid up at the airport, or whatever.

I can spend more time with the patients who need it. Isn’t that part of why I’m here?

Wearing Hawaiian shirts and shorts to the office everyday is also a plus (at least I think so).

It surprises me that more physicians aren’t willing to go into solo or small group practice. The big advantage is freedom, only needing to pay the overhead and your salary, and cover for others when needed.

The downside is financial. Like our hunting and gathering ancestors, you eat what you kill. If there’s a shortfall in cash flow, I’m the one who doesn’t get paid. It’s always good to have a line of credit available to fall back on in a pinch.

I can see why it’s daunting. Coming out of training you have loans to pay off. You may have a young family, and your first mortgage. You sure don’t want to take out another loan to start a private practice. The security of a guaranteed paycheck and no start-up costs is attractive. I was there, too, and I also took the first job I was offered back then.

There’s also the fear of suddenly working without a net for the first time in your career. It’s reassuring to get some added experience while being able to bounce a challenging case off another doctor. (I still do that, too, and always will.)

But no one tells me to upcode visits or add diagnostic codes just to get more money. Patients don’t call in panicked that they have an ICD-10 code for a condition no one told them they had.

At the end of the day I can tell the guy in the mirror that I’m doing my best.

Medicine has changed a lot over time ... but being a doctor hasn’t. The spark that led us all here is still there, somewhere, I hope. Go back and read Neighbor Rosicky by Willa Cather, and The Doctor Stories by William Carlos Williams.

In an age when technology is moving us forward, I think the practice of medicine should move backward, away from McDoctors Inc. A small, even solo, medical practice isn’t incompatible with the shiny toys of 2024 medicine. You can make good patient care happen with both.

Small practice isn’t for the faint of heart. I freely admit that it’s not for everyone.

But I wish more people would see it as a realistic option, and take the road less traveled.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.

Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.

This year, in fact, the VA has broken a number of its own records. The VA cites other high points:

• More than 127.5 million health care appointments, a 6% increase over last year;
• Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
• $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
• 2,517,519 disability benefit claims processed, a 27% increase over 2023;
• No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
• 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
• 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
• Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
• A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
• VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.

Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.

The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”  

“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”

The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.

Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.

This year, in fact, the VA has broken a number of its own records. The VA cites other high points:

• More than 127.5 million health care appointments, a 6% increase over last year;
• Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
• $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
• 2,517,519 disability benefit claims processed, a 27% increase over 2023;
• No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
• 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
• 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
• Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
• A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
• VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.

Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.

The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”  

“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”

The US Department of Veterans Affairs (VA) is earning high marks for the quality of care provided to veterans, according to multiple sources. For instance, systematic reviews published in 2023 found that VA health care is consistently as good as, or surpasses, non-VA health care. In the latest Centers for Medicare & Medicaid Services (CMS) annual Overall Hospital Quality Star Ratings, 67% of VA hospitals received either 4 or 5 stars, compared with only 41% of non-VA hospitals.

Veterans themselves are awarding high marks. According to the Medicare nationwide survey of patients, VA hospitals outperformed non-VA hospitals on all 10 core patient satisfaction metrics, including overall hospital rating, communication with doctors, communication about medications, and willingness to recommend the hospital. Furthermore, trust in VA outpatient care has reached an all-time record high of 92%, according to a survey of more than 440,000 veterans.

This year, in fact, the VA has broken a number of its own records. The VA cites other high points:

• More than 127.5 million health care appointments, a 6% increase over last year;
• Shorter wait times: new patients saw an 11% reduction in average wait times for VA primary care and a 7% reduction for mental health care compared to last year;
• $187 billion in benefits to 6.7 million veterans and survivors this year—an all-time record;
• 2,517,519 disability benefit claims processed, a 27% increase over 2023;
• No-cost emergency health care is provided to more than 50,000 veterans in acute suicidal crises; the Veterans Crisis Line supported 1,123,591 million calls, texts, and chats, up 12% from 2023;
• 47,925 veterans experiencing homelessness were housed in fiscal year 2024 and 96% remain housed long-term;
• 519,453 spouses and dependents received survivor benefits, a 4.5% increase from 2023;
• Services, resources, and assistance provided to a record 88,095 veteran family caregivers, an 18.6% increase over the 2023 record;
• A record 741,259 women veterans received compensation payments, 8.2% more than 2023;
• VA dental clinics provided > 6 million procedures to > 630,000 veterans; through community care, the VA delivered a record additional 3.4 million procedures to > 330,000 veterans.

Other actions this year include: expanding eligibility for VA healthcare to all toxin-exposed veterans years earlier than called for by the PACT Act; expanding access to care across the nation through VA Access Sprints, adding night and weekend clinics, and increasing the number of veterans scheduled into daily clinic schedules; removing copays for the first 3 outpatient mental health care and substance use disorder visits of each calendar year through 2027; expanding access to VA cancer care through establishing new cancer presumptive conditions, expanding access to genetic, lung, and colorectal cancer screening, and expanding the Close to Me cancer care program; expanding access to in vitro fertilization for eligible unmarried veterans and eligible veterans in same-sex marriages; expanding access to VA care and benefits for some former service members discharged under other than honorable conditions; and launching tele-emergency care for veterans nationwide.

The VA will continue to “aggressively reach out to and engage veterans to encourage them to come to VA for the care and benefits they have earned.”  

“Veterans deserve the very best from VA and our nation, and we will never settle for anything less,” said VA Secretary Denis McDonough. “We’re honored that more veterans are getting their earned health care and benefits from VA than ever before, but make no mistake: there is still work to do. We will continue to work each and every day to earn the trust of those we serve — and ensure that all Veterans, their families, and their survivors get the care and benefits they so rightly deserve.”

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

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

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

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

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

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

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

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

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

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

CHICAGO — A preview of much-anticipated updates to guidelines on managing thyroid disease in pregnancy shows key changes to recommendations in the evolving field, ranging from consideration of the chance of spontaneous normalization of thyroid levels during pregnancy to a heightened emphasis on shared decision-making and the nuances can factor into personalized treatment.

The guidelines, expected to be published in early 2025, have not been updated since 2017, and with substantial advances and evidence from countless studies since then, the new guidelines were developed with a goal to start afresh, said ATA Thyroid and Pregnancy Guidelines Task Force cochair Tim IM Korevaar, MD, PhD, in presenting the final draft guidelines at the American Thyroid Association (ATA) 2024 Meeting.

“Obviously, we’re not going to ignore the 2017 guidelines, which have been a very good resource for us so far, but we really wanted to start from scratch and follow a ‘blank canvas’ approach in optimizing the evidence,” said Korevaar, an endocrinologist and obstetric internist with the Division of Pharmacology and Vascular Medicine & Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

The guidelines, developed through a collaborative effort involving a wide variety of related medical societies, involved 14 systematic literature reviews. While the pregnancy issues covered by the guidelines is extensive, key highlights include:
 

Management in Preconception

Beginning with preconception, a key change in the guidelines will be that patients with euthyroid thyroid peroxidase (TPO) antibodies, which can be indicative of thyroid dysfunction, routine treatment with levothyroxine is not recommended, based on new evidence from randomized trials of high-risk patients showing no clear benefit from the treatment. 

“In these trials, and across analyses, there was absolutely no beneficial effect of levothyroxine in these patients [with euthyroid TPO antibody positivity],” he said.

With evidence showing, however, that TPO antibody positivity can lead to subclinical or overt hypothyroidism within 1 or 2 years, the guidelines will recommend that TPO antibody–positive patients do have thyroid stimulating hormone (TSH) levels tested every 3-6 months until pregnancy, and existing recommendations to test during pregnancy among those patients remain in place, Korevaar reported.

In terms of preconception subclinical hypothyroidism, the guidelines will emphasize the existing recommendation “to always strive to reassess” thyroid levels, and if subclinical hypothyroidism does persist, to treat with low-dose levothyroxine.
 

During Pregnancy

During pregnancy, the new proposed recommendations will reflect the important change that three key risk factors, including age over 30 years, having at least two prior pregnancies, and morbid obesity (body mass index [BMI] at least 40 kg/m²), previously considered a risk for thyroid dysfunction in pregnancy, should not, on their own, suggest the need for thyroid testing, based on low evidence of an increased risk in pregnancy.

Research on the issue includes a recent study from Korevaar’s team showing these factors to in fact have low predictability of thyroid dysfunction.

“We deemed that these risk differences weren’t really clinically meaningful (in predicting risk), and so we have removed to maternal age, BMI, and parity as risk factors for thyroid testing indications in pregnancy,” Korevaar said.

Factors considered a risk, resulting in recommended testing at presentation include a history of subclinical or clinical hypo- or hyperthyroidism, postpartum thyroiditis, known thyroid antibody positivity, symptoms of thyroid dysfunction or goiter, and other factors. 
 

Treatment for Subclinical Hypothyroidism in Pregnancy

Whereas current guidelines recommend TPO antibody status in determining when to consider treatment for subclinical hypothyroidism, the new proposed guideline will instead recommend treatment based on the timing of the diagnosis of the subclinical hypothyroidism, with consideration of treatment during the first trimester, but not in the second or third trimester, based on newer evidence of the absolute risk for pregnancy complications and randomized trial data.

“The recommendations are now to no longer based on TPO antibody status, but instead according to the timing of the diagnosis of subclinical hypothyroidism,” Korevaar said.

Based on the collective data, “due to the low risk, we do not recommend for routine levothyroxine treatment in the second or third trimester groups with TSH levels under 10 mU/L now.”

“However, for subclinical hypothyroidism diagnosed in the first trimester, the recommendation would be that you can consider levothyroxine treatment,” he said.

While a clear indication for treatment in any trimester is the presence of overt hypothyroidism, or TSH levels over 10 mU/L, Korevaar underscored the importance of considering nuances of the recommendations that may warrant flexibility, for instance among patients with borderline TSH levels.
 

Spontaneous Normalization of Thyroid Levels in Pregnancy

Another new recommendation addresses the issue of spontaneous normalization of abnormal thyroid function during pregnancy, with several large studies showing a large proportion of subclinical hypothyroidism cases spontaneously revert to euthyroidism by the third trimester — despite no treatment having been provided.

Under the important proposed recommendation, retesting of subclinical hypothyroidism is suggested within 3 weeks.

“The data shows that a large proportion of patients spontaneously revert to euthyroidism,” Korevaar said.

“Upon identifying subclinical hypothyroidism in the first trimester, there will be essentially two options that clinicians can discuss with their patient — one would be to consider confirmatory tests in 3 weeks or to discuss the starting the lower dose levothyroxine in the first trimester,” he said.

In terms of overt hypothyroidism, likewise, if patients have a TSH levels below 6 mU/L in pregnancy, “you can either consider doing confirmatory testing within 3 weeks, or discussing with the patient starting levothyroxine treatment,” Korevaar added.
 

Overt Hyperthyroidism

For overt hyperthyroidism, no significant changes from current guidelines are being proposed, with the key exception of a heightened emphasis on the need for shared decision-making with patients, Korevaar said.

“We want to emphasize shared decision-making especially for women who have Graves’ disease prior to pregnancy, because the antithyroid treatment modalities, primarily methimazole (MMI) and propylthiouracil (PTU), have different advantages and disadvantages for an upcoming pregnancy,” he said.

“If you help a patient become involved in the decision-making process, that can also be very helpful in managing the disease and following-up on the pregnancy.”

Under the recommendations, PTU remains the preferred drug in overt hyperthyroidism, due to a more favorable profile in terms of potential birth defects vs MMI, with research showing a higher absolute risk of 3% vs 5%.

The guidelines further suggest the option of stopping the antithyroid medications upon a positive pregnancy test, with the exception of high-risk patients.

Korevaar noted that, if the treatment is stopped early in pregnancy, relapse is not likely to occur until after approximately 3 months, or 12 weeks, at which time, the high-risk teratogenic period, which is between week 5 and week 15, will have passed.

Current guidelines regarding whether to stop treatment in higher-risk hyperthyroid patients are recommended to remain unchanged.
 

Thyroid Nodules and Cancer

Recommendations regarding thyroid nodules and cancer during pregnancy are also expected to remain largely similar to those in the 2017 guidelines, with the exception of an emphasis on simply considering how the patient would normally be managed outside of pregnancy. 

For instance, regarding the question of whether treatment can be withheld for 9 months during pregnancy. “A lot of times, the answer is yes,” Korevaar said.

Other topics that will be largely unchanged include issues of universal screening, definitions of normal and abnormal TSH and free T4 reference ranges and isolated hypothyroxinemia.
 

Steps Forward in Improving Updates, Readability

In addition to recommendation updates, the new guidelines are being revised to better reflect more recent evidence-based developments and user-friendliness.

“We have now made the step to a more systematic and replicable methodology to ensure for easier updates with a shorter interval,” Korevaar told this news organization.

“Furthermore, since 2006, the ATA guideline documents have followed a question-and-answer format, lacked recommendation tables and had none or only a few graphic illustrations,” he added. 

“We are now further developing the typical outline of the guidelines to improve the readability and dissemination of the guideline document.”

Korevaar’s disclosures include lectureship fees from IBSA, Merck, and Berlin Chemie.

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

TOPLINE:

Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
• The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
• Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
• Data sources included online databases with data up to January 2024, reference lists, and hand searches.
• The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.

TAKEAWAY:

• Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
• Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
• Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
• Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).

IN PRACTICE:

“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.

SOURCE:

This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.

DISCLOSURES:

This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
• The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
• Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
• Data sources included online databases with data up to January 2024, reference lists, and hand searches.
• The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.

TAKEAWAY:

• Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
• Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
• Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
• Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).

IN PRACTICE:

“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.

SOURCE:

This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.

DISCLOSURES:

This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Postpartum exercise reduces the severity of depressive and anxiety symptoms. Initiating exercise within 12 weeks post partum is linked to greater reductions in depressive symptoms.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis including 35 studies with a total of 4072 participants.
• The review included randomized controlled trials and nonrandomized interventions examining the impact of postpartum exercise on depression and anxiety.
• Participants were postpartum individuals within the first year after childbirth, with interventions including various types of exercise.
• Data sources included online databases with data up to January 2024, reference lists, and hand searches.
• The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess the certainty of evidence.

TAKEAWAY:

• Postpartum exercise-only interventions resulted in a moderate reduction in the severity of depressive symptoms (standardized mean difference [SMD], –0.52; 95% CI, –0.80 to –0.24).
• Exercise-only interventions were associated with a small reduction in the severity of anxiety symptoms (SMD, –0.25; 95% CI, –0.43 to –0.08).
• Initiating exercise within 12 weeks post partum was associated with a greater reduction in depressive symptoms, compared with starting later.
• Postpartum exercise was associated with a 45% reduction in the odds of developing depression (odds ratio, 0.55; 95% CI, 0.32-0.95).

IN PRACTICE:

“Further investigation should aim to investigate the effects of postpartum exercise in individuals who experienced perinatal complications and in those who had limitations to exercise during pregnancy. Additionally, more investigation is required to address the possible lasting effects of postpartum exercise on maternal mental health as there were very limited studies reporting on this outcome,” the authors of the study wrote.

SOURCE:

This study was led by Margie H. Davenport, University of Alberta in Edmonton, Canada. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

This study’s limitations included high heterogeneity among included studies, small sample sizes in some studies, and the combination of exercise with other interventions in some cases. These factors may have affected the generalizability and precision of the findings.

DISCLOSURES:

This study was funded by the Christenson Professorship in Active Healthy Living. Davenport is funded by a Christenson Professorship in Active Healthy Living. One coauthor is funded by the Université du Québec à Trois-Rivières research chair in physical activity and maternal and neonatal health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Mental health, family planning, and career aspirations are among the unique challenges faced by younger adults diagnosed with colorectal cancer (CRC) — issues that may not be adequately addressed by cancer care providers, a new survey showed.

“We tend to think of cancer as a disease of older populations, but it’s impacting younger people who are in important developmental stages of their lives,” said Samantha Savitch, MD, in a podcast from the American College of Surgeons (ACS) Clinical Congress 2024, where she presented her research.

In fact, since 1994, cases of young-onset CRC have increased by more than 50%, according to the National Cancer Institute.

“Our goal with the study was to better understand what young adults with colorectal cancer really care about, so that we can ensure that we’re properly addressing their needs as part of like comprehensive cancer care,” Savitch, with the University of Michigan, Ann Arbor, Michigan, explained.

The researchers interviewed a sample of 35 patients who were diagnosed with CRC before the age of 50 years. The researchers asked patients open-ended questions about the influence their CRC diagnosis had on their lives, the daily challenges they experienced, as well as concerns about the future.

Patients expressed the greatest concern about four areas of health and well-being: Physical health, mental health, family planning, and career.

For physical health, patients worried about incontinence, loss of vitality, and expenses related to healthcare. On the mental health front, patients expressed concern about the uncertainty surrounding long-term survival and anxiety about the timing of their diagnosis. Family planning was a key issue as well, with patients highlighting uncertainties about fertility after chemotherapy. On the career front, patients also noted concerns surrounding job security, challenges pursuing advanced degrees, and a reliance on benefits from employment.

These concerns were not gender-specific. Career, physical health, financial security, mental health, fertility, and family planning were equally important to men and women.

Savitch provided a sample of quotes from interviewees that illustrated their specific concerns in each category.

A 47-year-old man reflected on his physical health now that his rectum is gone. “I no longer have that feeling of sensation like in my cheeks; basically, the cheeks and the anus area is all dead,” he said. A 48-year-old woman discussed the havoc chemotherapy wrecked on her teeth. “I don’t want to get emotional, I just went to the dentist yesterday, and I just get so frustrated ... All these things to pay. I should be happy to be alive,” she said. But “I have so much money in my mouth.”

On the mental health front, a 34-year-old woman described the fear she felt about a cancer recurrence following the birth of her daughter. After a CT scan, she had to experience 2 weeks of limbo, thinking, “I have cancer again.” She had begun a journal dedicated to her daughter in case she had a recurrence and died. “I always think that I am going to die. I think about death every day.”

Reflecting on her future fertility, a 22-year-old woman recalled the uncertainty surrounding whether chemotherapy would affect her ability to have children. “I would get really nervous,” she said, “so I was like, ‘I will do the injections. I just want to save a few of my eggs just in case.’ ” A 33-year-old man opted not to freeze his sperm because “I didn’t know if I was going to live or die, I didn’t know anything ... I barely had any money. So, like, do I risk putting this money up to freeze something when I don’t even know if I am going to be here or not?”

On the career front, a 48-year-old man highlighted how his cancer completely changed his family’s life.”I went from being a provider for my family, making enough money to take care of my family, where my wife was staying home, to now not being able to work and her having to pick up little side jobs and stuff just to try to help make ends meet.”

“These aspects of cancer care are rarely discussed, so it is important to acknowledge that patients care about fertility and family planning, their career aspirations, building assets — all things they must put on hold because of their cancer diagnosis,” Savitch said in a news release.

“This goes beyond just colorectal cancer,” Savitch added. “There are a lot of patients experiencing similar challenges, so we need more research to better understand these issues in patients with colorectal cancer as well as other cancers and, ultimately, to restructure our comprehensive cancer programs to make sure we are treating the patient and not just the disease.”

Support for the study was provided by the Rogel Cancer Center at the University of Michigan. Savitch had no relevant disclosures.

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

Mental health, family planning, and career aspirations are among the unique challenges faced by younger adults diagnosed with colorectal cancer (CRC) — issues that may not be adequately addressed by cancer care providers, a new survey showed.

“We tend to think of cancer as a disease of older populations, but it’s impacting younger people who are in important developmental stages of their lives,” said Samantha Savitch, MD, in a podcast from the American College of Surgeons (ACS) Clinical Congress 2024, where she presented her research.

In fact, since 1994, cases of young-onset CRC have increased by more than 50%, according to the National Cancer Institute.

“Our goal with the study was to better understand what young adults with colorectal cancer really care about, so that we can ensure that we’re properly addressing their needs as part of like comprehensive cancer care,” Savitch, with the University of Michigan, Ann Arbor, Michigan, explained.

The researchers interviewed a sample of 35 patients who were diagnosed with CRC before the age of 50 years. The researchers asked patients open-ended questions about the influence their CRC diagnosis had on their lives, the daily challenges they experienced, as well as concerns about the future.

Patients expressed the greatest concern about four areas of health and well-being: Physical health, mental health, family planning, and career.

For physical health, patients worried about incontinence, loss of vitality, and expenses related to healthcare. On the mental health front, patients expressed concern about the uncertainty surrounding long-term survival and anxiety about the timing of their diagnosis. Family planning was a key issue as well, with patients highlighting uncertainties about fertility after chemotherapy. On the career front, patients also noted concerns surrounding job security, challenges pursuing advanced degrees, and a reliance on benefits from employment.

These concerns were not gender-specific. Career, physical health, financial security, mental health, fertility, and family planning were equally important to men and women.

Savitch provided a sample of quotes from interviewees that illustrated their specific concerns in each category.

A 47-year-old man reflected on his physical health now that his rectum is gone. “I no longer have that feeling of sensation like in my cheeks; basically, the cheeks and the anus area is all dead,” he said. A 48-year-old woman discussed the havoc chemotherapy wrecked on her teeth. “I don’t want to get emotional, I just went to the dentist yesterday, and I just get so frustrated ... All these things to pay. I should be happy to be alive,” she said. But “I have so much money in my mouth.”

On the mental health front, a 34-year-old woman described the fear she felt about a cancer recurrence following the birth of her daughter. After a CT scan, she had to experience 2 weeks of limbo, thinking, “I have cancer again.” She had begun a journal dedicated to her daughter in case she had a recurrence and died. “I always think that I am going to die. I think about death every day.”

Reflecting on her future fertility, a 22-year-old woman recalled the uncertainty surrounding whether chemotherapy would affect her ability to have children. “I would get really nervous,” she said, “so I was like, ‘I will do the injections. I just want to save a few of my eggs just in case.’ ” A 33-year-old man opted not to freeze his sperm because “I didn’t know if I was going to live or die, I didn’t know anything ... I barely had any money. So, like, do I risk putting this money up to freeze something when I don’t even know if I am going to be here or not?”

On the career front, a 48-year-old man highlighted how his cancer completely changed his family’s life.”I went from being a provider for my family, making enough money to take care of my family, where my wife was staying home, to now not being able to work and her having to pick up little side jobs and stuff just to try to help make ends meet.”

“These aspects of cancer care are rarely discussed, so it is important to acknowledge that patients care about fertility and family planning, their career aspirations, building assets — all things they must put on hold because of their cancer diagnosis,” Savitch said in a news release.

“This goes beyond just colorectal cancer,” Savitch added. “There are a lot of patients experiencing similar challenges, so we need more research to better understand these issues in patients with colorectal cancer as well as other cancers and, ultimately, to restructure our comprehensive cancer programs to make sure we are treating the patient and not just the disease.”

Support for the study was provided by the Rogel Cancer Center at the University of Michigan. Savitch had no relevant disclosures.

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

Mental health, family planning, and career aspirations are among the unique challenges faced by younger adults diagnosed with colorectal cancer (CRC) — issues that may not be adequately addressed by cancer care providers, a new survey showed.

“We tend to think of cancer as a disease of older populations, but it’s impacting younger people who are in important developmental stages of their lives,” said Samantha Savitch, MD, in a podcast from the American College of Surgeons (ACS) Clinical Congress 2024, where she presented her research.

In fact, since 1994, cases of young-onset CRC have increased by more than 50%, according to the National Cancer Institute.

“Our goal with the study was to better understand what young adults with colorectal cancer really care about, so that we can ensure that we’re properly addressing their needs as part of like comprehensive cancer care,” Savitch, with the University of Michigan, Ann Arbor, Michigan, explained.

The researchers interviewed a sample of 35 patients who were diagnosed with CRC before the age of 50 years. The researchers asked patients open-ended questions about the influence their CRC diagnosis had on their lives, the daily challenges they experienced, as well as concerns about the future.

Patients expressed the greatest concern about four areas of health and well-being: Physical health, mental health, family planning, and career.

For physical health, patients worried about incontinence, loss of vitality, and expenses related to healthcare. On the mental health front, patients expressed concern about the uncertainty surrounding long-term survival and anxiety about the timing of their diagnosis. Family planning was a key issue as well, with patients highlighting uncertainties about fertility after chemotherapy. On the career front, patients also noted concerns surrounding job security, challenges pursuing advanced degrees, and a reliance on benefits from employment.

These concerns were not gender-specific. Career, physical health, financial security, mental health, fertility, and family planning were equally important to men and women.

Savitch provided a sample of quotes from interviewees that illustrated their specific concerns in each category.

A 47-year-old man reflected on his physical health now that his rectum is gone. “I no longer have that feeling of sensation like in my cheeks; basically, the cheeks and the anus area is all dead,” he said. A 48-year-old woman discussed the havoc chemotherapy wrecked on her teeth. “I don’t want to get emotional, I just went to the dentist yesterday, and I just get so frustrated ... All these things to pay. I should be happy to be alive,” she said. But “I have so much money in my mouth.”

On the mental health front, a 34-year-old woman described the fear she felt about a cancer recurrence following the birth of her daughter. After a CT scan, she had to experience 2 weeks of limbo, thinking, “I have cancer again.” She had begun a journal dedicated to her daughter in case she had a recurrence and died. “I always think that I am going to die. I think about death every day.”

Reflecting on her future fertility, a 22-year-old woman recalled the uncertainty surrounding whether chemotherapy would affect her ability to have children. “I would get really nervous,” she said, “so I was like, ‘I will do the injections. I just want to save a few of my eggs just in case.’ ” A 33-year-old man opted not to freeze his sperm because “I didn’t know if I was going to live or die, I didn’t know anything ... I barely had any money. So, like, do I risk putting this money up to freeze something when I don’t even know if I am going to be here or not?”

On the career front, a 48-year-old man highlighted how his cancer completely changed his family’s life.”I went from being a provider for my family, making enough money to take care of my family, where my wife was staying home, to now not being able to work and her having to pick up little side jobs and stuff just to try to help make ends meet.”

“These aspects of cancer care are rarely discussed, so it is important to acknowledge that patients care about fertility and family planning, their career aspirations, building assets — all things they must put on hold because of their cancer diagnosis,” Savitch said in a news release.

“This goes beyond just colorectal cancer,” Savitch added. “There are a lot of patients experiencing similar challenges, so we need more research to better understand these issues in patients with colorectal cancer as well as other cancers and, ultimately, to restructure our comprehensive cancer programs to make sure we are treating the patient and not just the disease.”

Support for the study was provided by the Rogel Cancer Center at the University of Michigan. Savitch had no relevant disclosures.

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

The US Food and Drug Administration (FDA) has approved obecabtagene autoleucel, or obe-cel (AUTO1, Autolus Therapeutics) for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).

Approval of the CD19 chimeric antigen receptor T-cell therapy (CAR T) — which, according to Autolus, was specifically “designed to have a ‘fast-off’ kinetic” to minimize excessive activation of the programmed T cells and thereby increase T-cell persistence and reduce T-cell exhaustion — was based on efficacy and safety findings from the open-label, single-arm FELIX study. 

Initial study findings were presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, and updated findings from a pooled analysis of FELIX phase 1b/2 data were presented at the 2023 American Society of Hematology conference.

The pooled analysis showed a complete response (CR) or CR with incomplete hematologic recovery (CR/CRi) rate of 77% and a CR rate of 57% at a median follow up of 11 months in 124 patients treated between September 2020 and December 2022.

Among evaluable patients, 96% achieved minimal residual disease (MRD)-negative status. Median duration of response was not reached.

Safety findings showed a low 2.4% and 7.1% rate of grade 3 or higher cytokine release syndrome (CRS) and/or grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. 

FELIX study participants were 18 years of age or older with relapsed/refractory B-cell ALL and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients underwent lymphodepletion with fludarabine as 4 x 30 mg/m² and cyclophosphamide at 2 x 500 mg/m². Obe-cel was administered at a target dose of 410 x 10⁶ CAR T cells as a split dose on days 1 and 10 based on pre-lymphodepletion bone marrow blast burden.

CAR T expansion was similar across the study cohorts, and CAR T persistence was ongoing in most responders at follow-up. 

A particular benefit was observed in patients’ low leukemia burden, defined as morphological remission per investigator assessment (less than 5% bone marrow blasts without extramedullary disease) as measured at screening or at the start of lymphodepletion, prior to obe-cel infusion.

For example, of 10 evaluable patients with MRD at screening, nine achieved CR or Cri, and all 10 achieved MRD-negative status after infusion. Median duration of response was not reached; no grade 3 or higher CRS occurred; and one patient had grade 3 or higher ICANS. And in a subset of 27 evaluable patients in morphological remission at the time of lymphodepletion, 24 (89%) achieved CR/CRi, and 100% of MRD evaluable responders achieved MRD negative CR/CRi after infusion. In this subset, median duration of response was not reached, and no patients experienced grade 3 or higher CRS or ICANS. 

Autolus Technologies announced in January 2024 that the FDA had accepted its Biologics License Application for obe-cel and noted the treatment had also been granted Orphan Drug Designation by the FDA. 

In June 2024, an additional update presented at the annual ASCO meeting showed that 12-month event-free survival was 50% and 43% with or without censoring for consolidative stem cell transplant or new therapies, respectively, and overall survival was 61% and 59%, respectively. 

Ongoing CAR T-cell persistency and B-cell aplasia were associated with improved event-free survival without further consolidation after obe-cel infusion, the investigators reported, noting that consolidative stem cell transplant for those in MRD-negative remission did not improve event-free survival or overall survival at 12 months. 

In a commentary, Jorge Cortes, MD, director of the Georgia Cancer Center, Augusta, said the findings presented at ASCO suggest that obe-cel is “very promising and may [represent] a different strategy that decreases the toxicity for CAR T cells.” 

The study was funded by Merck. Smith reports receiving grant funding from Merck. Jones reports no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved obecabtagene autoleucel, or obe-cel (AUTO1, Autolus Therapeutics) for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).

Approval of the CD19 chimeric antigen receptor T-cell therapy (CAR T) — which, according to Autolus, was specifically “designed to have a ‘fast-off’ kinetic” to minimize excessive activation of the programmed T cells and thereby increase T-cell persistence and reduce T-cell exhaustion — was based on efficacy and safety findings from the open-label, single-arm FELIX study. 

Initial study findings were presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, and updated findings from a pooled analysis of FELIX phase 1b/2 data were presented at the 2023 American Society of Hematology conference.

The pooled analysis showed a complete response (CR) or CR with incomplete hematologic recovery (CR/CRi) rate of 77% and a CR rate of 57% at a median follow up of 11 months in 124 patients treated between September 2020 and December 2022.

Among evaluable patients, 96% achieved minimal residual disease (MRD)-negative status. Median duration of response was not reached.

Safety findings showed a low 2.4% and 7.1% rate of grade 3 or higher cytokine release syndrome (CRS) and/or grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. 

FELIX study participants were 18 years of age or older with relapsed/refractory B-cell ALL and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients underwent lymphodepletion with fludarabine as 4 x 30 mg/m² and cyclophosphamide at 2 x 500 mg/m². Obe-cel was administered at a target dose of 410 x 10⁶ CAR T cells as a split dose on days 1 and 10 based on pre-lymphodepletion bone marrow blast burden.

CAR T expansion was similar across the study cohorts, and CAR T persistence was ongoing in most responders at follow-up. 

A particular benefit was observed in patients’ low leukemia burden, defined as morphological remission per investigator assessment (less than 5% bone marrow blasts without extramedullary disease) as measured at screening or at the start of lymphodepletion, prior to obe-cel infusion.

For example, of 10 evaluable patients with MRD at screening, nine achieved CR or Cri, and all 10 achieved MRD-negative status after infusion. Median duration of response was not reached; no grade 3 or higher CRS occurred; and one patient had grade 3 or higher ICANS. And in a subset of 27 evaluable patients in morphological remission at the time of lymphodepletion, 24 (89%) achieved CR/CRi, and 100% of MRD evaluable responders achieved MRD negative CR/CRi after infusion. In this subset, median duration of response was not reached, and no patients experienced grade 3 or higher CRS or ICANS. 

Autolus Technologies announced in January 2024 that the FDA had accepted its Biologics License Application for obe-cel and noted the treatment had also been granted Orphan Drug Designation by the FDA. 

In June 2024, an additional update presented at the annual ASCO meeting showed that 12-month event-free survival was 50% and 43% with or without censoring for consolidative stem cell transplant or new therapies, respectively, and overall survival was 61% and 59%, respectively. 

Ongoing CAR T-cell persistency and B-cell aplasia were associated with improved event-free survival without further consolidation after obe-cel infusion, the investigators reported, noting that consolidative stem cell transplant for those in MRD-negative remission did not improve event-free survival or overall survival at 12 months. 

In a commentary, Jorge Cortes, MD, director of the Georgia Cancer Center, Augusta, said the findings presented at ASCO suggest that obe-cel is “very promising and may [represent] a different strategy that decreases the toxicity for CAR T cells.” 

The study was funded by Merck. Smith reports receiving grant funding from Merck. Jones reports no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved obecabtagene autoleucel, or obe-cel (AUTO1, Autolus Therapeutics) for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).

Approval of the CD19 chimeric antigen receptor T-cell therapy (CAR T) — which, according to Autolus, was specifically “designed to have a ‘fast-off’ kinetic” to minimize excessive activation of the programmed T cells and thereby increase T-cell persistence and reduce T-cell exhaustion — was based on efficacy and safety findings from the open-label, single-arm FELIX study. 

Initial study findings were presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting, and updated findings from a pooled analysis of FELIX phase 1b/2 data were presented at the 2023 American Society of Hematology conference.

The pooled analysis showed a complete response (CR) or CR with incomplete hematologic recovery (CR/CRi) rate of 77% and a CR rate of 57% at a median follow up of 11 months in 124 patients treated between September 2020 and December 2022.

Among evaluable patients, 96% achieved minimal residual disease (MRD)-negative status. Median duration of response was not reached.

Safety findings showed a low 2.4% and 7.1% rate of grade 3 or higher cytokine release syndrome (CRS) and/or grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. 

FELIX study participants were 18 years of age or older with relapsed/refractory B-cell ALL and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients underwent lymphodepletion with fludarabine as 4 x 30 mg/m² and cyclophosphamide at 2 x 500 mg/m². Obe-cel was administered at a target dose of 410 x 10⁶ CAR T cells as a split dose on days 1 and 10 based on pre-lymphodepletion bone marrow blast burden.

CAR T expansion was similar across the study cohorts, and CAR T persistence was ongoing in most responders at follow-up. 

A particular benefit was observed in patients’ low leukemia burden, defined as morphological remission per investigator assessment (less than 5% bone marrow blasts without extramedullary disease) as measured at screening or at the start of lymphodepletion, prior to obe-cel infusion.

For example, of 10 evaluable patients with MRD at screening, nine achieved CR or Cri, and all 10 achieved MRD-negative status after infusion. Median duration of response was not reached; no grade 3 or higher CRS occurred; and one patient had grade 3 or higher ICANS. And in a subset of 27 evaluable patients in morphological remission at the time of lymphodepletion, 24 (89%) achieved CR/CRi, and 100% of MRD evaluable responders achieved MRD negative CR/CRi after infusion. In this subset, median duration of response was not reached, and no patients experienced grade 3 or higher CRS or ICANS. 

Autolus Technologies announced in January 2024 that the FDA had accepted its Biologics License Application for obe-cel and noted the treatment had also been granted Orphan Drug Designation by the FDA. 

In June 2024, an additional update presented at the annual ASCO meeting showed that 12-month event-free survival was 50% and 43% with or without censoring for consolidative stem cell transplant or new therapies, respectively, and overall survival was 61% and 59%, respectively. 

Ongoing CAR T-cell persistency and B-cell aplasia were associated with improved event-free survival without further consolidation after obe-cel infusion, the investigators reported, noting that consolidative stem cell transplant for those in MRD-negative remission did not improve event-free survival or overall survival at 12 months. 

In a commentary, Jorge Cortes, MD, director of the Georgia Cancer Center, Augusta, said the findings presented at ASCO suggest that obe-cel is “very promising and may [represent] a different strategy that decreases the toxicity for CAR T cells.” 

The study was funded by Merck. Smith reports receiving grant funding from Merck. Jones reports no relevant financial relationships.

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