Rare Diseases

TOPLINE:

Gastrointestinal involvement is common in childhood-onset lupus, with more than half of the patients presenting with gastrointestinal symptoms at diagnosis. Abdominal pain and elevated hepatic transaminases are the most common initial signs.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to explore the prevalence and characteristics of gastrointestinal involvement in childhood-onset systemic lupus erythematosus (SLE).
• They included 123 patients aged ≤ 18 years (82.1% girls) with childhood-onset SLE from 16 referral departments of pediatric rheumatology in Turkey who showed gastrointestinal system (GIS) involvement either during diagnosis or the course of the disease.
• The mean age at diagnosis was 12.5 years, and the median follow-up duration was 44.5 months.
• Demographic information, clinical manifestations, laboratory findings, radiological and endoscopic assessments, histopathologic analyses, treatments, and clinical outcomes were retrospectively extracted from patient records; disease activity and cumulative organ damage were also assessed.

TAKEAWAY:

• At the time of SLE diagnosis, 63.4% of patients presented with gastrointestinal involvement, while others (36.6%) developed gastrointestinal symptoms after a median of 12 months.
• Abdominal pain was the most common initial symptom, observed in 62.6% of patients, followed by elevated hepatic transaminases in 56.9%.
• The most common type of gastrointestinal involvement was autoimmune hepatitis (25.2%), followed by hepatic steatosis (13%), and lupus hepatitis (11.3%).
• The gastrointestinal manifestations were directly attributed to SLE in 82 patients, were drug related in 35 patients, and caused by comorbidities in 6 patients.

IN PRACTICE:

“It is crucial to consider SLE in the differential diagnosis of GIS [gastrointestinal system] manifestations in children. The inclusion of GIS involvement as a new diagnostic criterion may be warranted, given its potential prevalence that might be higher than currently recognized,” the authors wrote.

SOURCE:

This study was led by Hafize Emine Sönmez, MD, Department of Pediatric Rheumatology, Kocaeli University, İzmit, Turkey, and was published online in Lupus. 

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between gastrointestinal symptoms and SLE. This study also did not include a comparison between patients with childhood-onset SLE with gastrointestinal involvement and those without. Moreover, the study relied on patient records for data collection, which may have introduced bias.

DISCLOSURES:

This study did not receive any financial support. The authors declared no potential conflict of interest.

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:

Gastrointestinal involvement is common in childhood-onset lupus, with more than half of the patients presenting with gastrointestinal symptoms at diagnosis. Abdominal pain and elevated hepatic transaminases are the most common initial signs.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to explore the prevalence and characteristics of gastrointestinal involvement in childhood-onset systemic lupus erythematosus (SLE).
• They included 123 patients aged ≤ 18 years (82.1% girls) with childhood-onset SLE from 16 referral departments of pediatric rheumatology in Turkey who showed gastrointestinal system (GIS) involvement either during diagnosis or the course of the disease.
• The mean age at diagnosis was 12.5 years, and the median follow-up duration was 44.5 months.
• Demographic information, clinical manifestations, laboratory findings, radiological and endoscopic assessments, histopathologic analyses, treatments, and clinical outcomes were retrospectively extracted from patient records; disease activity and cumulative organ damage were also assessed.

TAKEAWAY:

• At the time of SLE diagnosis, 63.4% of patients presented with gastrointestinal involvement, while others (36.6%) developed gastrointestinal symptoms after a median of 12 months.
• Abdominal pain was the most common initial symptom, observed in 62.6% of patients, followed by elevated hepatic transaminases in 56.9%.
• The most common type of gastrointestinal involvement was autoimmune hepatitis (25.2%), followed by hepatic steatosis (13%), and lupus hepatitis (11.3%).
• The gastrointestinal manifestations were directly attributed to SLE in 82 patients, were drug related in 35 patients, and caused by comorbidities in 6 patients.

IN PRACTICE:

“It is crucial to consider SLE in the differential diagnosis of GIS [gastrointestinal system] manifestations in children. The inclusion of GIS involvement as a new diagnostic criterion may be warranted, given its potential prevalence that might be higher than currently recognized,” the authors wrote.

SOURCE:

This study was led by Hafize Emine Sönmez, MD, Department of Pediatric Rheumatology, Kocaeli University, İzmit, Turkey, and was published online in Lupus. 

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between gastrointestinal symptoms and SLE. This study also did not include a comparison between patients with childhood-onset SLE with gastrointestinal involvement and those without. Moreover, the study relied on patient records for data collection, which may have introduced bias.

DISCLOSURES:

This study did not receive any financial support. The authors declared no potential conflict of interest.

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:

Gastrointestinal involvement is common in childhood-onset lupus, with more than half of the patients presenting with gastrointestinal symptoms at diagnosis. Abdominal pain and elevated hepatic transaminases are the most common initial signs.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to explore the prevalence and characteristics of gastrointestinal involvement in childhood-onset systemic lupus erythematosus (SLE).
• They included 123 patients aged ≤ 18 years (82.1% girls) with childhood-onset SLE from 16 referral departments of pediatric rheumatology in Turkey who showed gastrointestinal system (GIS) involvement either during diagnosis or the course of the disease.
• The mean age at diagnosis was 12.5 years, and the median follow-up duration was 44.5 months.
• Demographic information, clinical manifestations, laboratory findings, radiological and endoscopic assessments, histopathologic analyses, treatments, and clinical outcomes were retrospectively extracted from patient records; disease activity and cumulative organ damage were also assessed.

TAKEAWAY:

• At the time of SLE diagnosis, 63.4% of patients presented with gastrointestinal involvement, while others (36.6%) developed gastrointestinal symptoms after a median of 12 months.
• Abdominal pain was the most common initial symptom, observed in 62.6% of patients, followed by elevated hepatic transaminases in 56.9%.
• The most common type of gastrointestinal involvement was autoimmune hepatitis (25.2%), followed by hepatic steatosis (13%), and lupus hepatitis (11.3%).
• The gastrointestinal manifestations were directly attributed to SLE in 82 patients, were drug related in 35 patients, and caused by comorbidities in 6 patients.

IN PRACTICE:

“It is crucial to consider SLE in the differential diagnosis of GIS [gastrointestinal system] manifestations in children. The inclusion of GIS involvement as a new diagnostic criterion may be warranted, given its potential prevalence that might be higher than currently recognized,” the authors wrote.

SOURCE:

This study was led by Hafize Emine Sönmez, MD, Department of Pediatric Rheumatology, Kocaeli University, İzmit, Turkey, and was published online in Lupus. 

LIMITATIONS:

The retrospective nature of the study may have limited the ability to establish causality between gastrointestinal symptoms and SLE. This study also did not include a comparison between patients with childhood-onset SLE with gastrointestinal involvement and those without. Moreover, the study relied on patient records for data collection, which may have introduced bias.

DISCLOSURES:

This study did not receive any financial support. The authors declared no potential conflict of interest.

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:

Mobile images may be reliable for assessing cutaneous neurofibroma (cNF) features in patients with neurofibromatosis type 1 (NF1), according to a crowd-sourced registry study that also suggests correlations between cNF burden and quality of life (QoL), particularly the impact of facial severity on emotional well-being.

METHODOLOGY:

• To learn more about the association of cNFs with QoL, pain, and itch in patients with this rare disease, researchers enrolled 1016 individuals aged 40 years and older with NF1 who had at least one cNF, from May 2021 to December 2023, after reaching out to patient-led or NF1 advocacy organizations in 13 countries, including the United States.
• Participants provided demographic data, detailed photographs, and saliva samples for genetic sequencing, with 583 participants (mean age, 51.7 years; 65.9% women) submitting high-quality photographs from seven body regions at the time of the study analysis.
• A subset of 50 participants also underwent whole-body imaging.
• Four researchers independently rated the photographs for various cNF features, including general severity, number, size, facial severity, and subtypes.

TAKEAWAY:

• Based on evaluations by NF1 specialists, the agreement between mobile and whole-body images was “substantial” (74%-88% agreement) for the number of cNFs, general severity, and facial severity. Agreement between self-reported numbers of cNFs and investigator-rated numbers based on photographs was “minimal to fair.”
• Female sex, the number of cNFs, severity of cNFs on the face, and globular cNFs were associated with worse QoL (based on Skindex scores); severity of cNFs on the face had the strongest impact on overall QoL (P < .001).
• An increasing number of cNFs and worsening facial severity were strongly correlated with higher emotion subdomain scores.
• A higher number of cNFs, more severe cNFs on the face, and larger cNFs were all slightly associated with increased itch and pain (P < .01).

IN PRACTICE:

“To develop effective therapeutics, meaningful clinical outcomes that are tied with improvement in QoL for persons with NF1 must be clearly defined,” the authors wrote. The results of this study, they added, “suggested the benefit of this crowd-sourced resource by identifying the features of cNFs with the greatest association with QoL and symptoms of pain and itch in persons with NF1, highlighting new intervention strategies and features to target to most improve QoL in NF1.”

SOURCE:

The study was led by Michelle Jade Lin, BS, Stanford University School of Medicine, Redwood City, California, and was published online in JAMA Dermatology.

LIMITATIONS:

The study included only a small number of individuals from racial and ethnic minority groups and did not capture ethnicity information, which could have provided further insights into disease impact across different demographics.

DISCLOSURES:

This study was supported by Johns Hopkins University, Baltimore, and the Bloomberg Family Foundation. Ms. Lin reported support from the Stanford Medical Scholars Research Program. Three authors reported personal fees or grants outside this work. Other authors reported no competing interests.

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:

Mobile images may be reliable for assessing cutaneous neurofibroma (cNF) features in patients with neurofibromatosis type 1 (NF1), according to a crowd-sourced registry study that also suggests correlations between cNF burden and quality of life (QoL), particularly the impact of facial severity on emotional well-being.

METHODOLOGY:

• To learn more about the association of cNFs with QoL, pain, and itch in patients with this rare disease, researchers enrolled 1016 individuals aged 40 years and older with NF1 who had at least one cNF, from May 2021 to December 2023, after reaching out to patient-led or NF1 advocacy organizations in 13 countries, including the United States.
• Participants provided demographic data, detailed photographs, and saliva samples for genetic sequencing, with 583 participants (mean age, 51.7 years; 65.9% women) submitting high-quality photographs from seven body regions at the time of the study analysis.
• A subset of 50 participants also underwent whole-body imaging.
• Four researchers independently rated the photographs for various cNF features, including general severity, number, size, facial severity, and subtypes.

TAKEAWAY:

• Based on evaluations by NF1 specialists, the agreement between mobile and whole-body images was “substantial” (74%-88% agreement) for the number of cNFs, general severity, and facial severity. Agreement between self-reported numbers of cNFs and investigator-rated numbers based on photographs was “minimal to fair.”
• Female sex, the number of cNFs, severity of cNFs on the face, and globular cNFs were associated with worse QoL (based on Skindex scores); severity of cNFs on the face had the strongest impact on overall QoL (P < .001).
• An increasing number of cNFs and worsening facial severity were strongly correlated with higher emotion subdomain scores.
• A higher number of cNFs, more severe cNFs on the face, and larger cNFs were all slightly associated with increased itch and pain (P < .01).

IN PRACTICE:

“To develop effective therapeutics, meaningful clinical outcomes that are tied with improvement in QoL for persons with NF1 must be clearly defined,” the authors wrote. The results of this study, they added, “suggested the benefit of this crowd-sourced resource by identifying the features of cNFs with the greatest association with QoL and symptoms of pain and itch in persons with NF1, highlighting new intervention strategies and features to target to most improve QoL in NF1.”

SOURCE:

The study was led by Michelle Jade Lin, BS, Stanford University School of Medicine, Redwood City, California, and was published online in JAMA Dermatology.

LIMITATIONS:

The study included only a small number of individuals from racial and ethnic minority groups and did not capture ethnicity information, which could have provided further insights into disease impact across different demographics.

DISCLOSURES:

This study was supported by Johns Hopkins University, Baltimore, and the Bloomberg Family Foundation. Ms. Lin reported support from the Stanford Medical Scholars Research Program. Three authors reported personal fees or grants outside this work. Other authors reported no competing interests.

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:

Mobile images may be reliable for assessing cutaneous neurofibroma (cNF) features in patients with neurofibromatosis type 1 (NF1), according to a crowd-sourced registry study that also suggests correlations between cNF burden and quality of life (QoL), particularly the impact of facial severity on emotional well-being.

METHODOLOGY:

• To learn more about the association of cNFs with QoL, pain, and itch in patients with this rare disease, researchers enrolled 1016 individuals aged 40 years and older with NF1 who had at least one cNF, from May 2021 to December 2023, after reaching out to patient-led or NF1 advocacy organizations in 13 countries, including the United States.
• Participants provided demographic data, detailed photographs, and saliva samples for genetic sequencing, with 583 participants (mean age, 51.7 years; 65.9% women) submitting high-quality photographs from seven body regions at the time of the study analysis.
• A subset of 50 participants also underwent whole-body imaging.
• Four researchers independently rated the photographs for various cNF features, including general severity, number, size, facial severity, and subtypes.

TAKEAWAY:

• Based on evaluations by NF1 specialists, the agreement between mobile and whole-body images was “substantial” (74%-88% agreement) for the number of cNFs, general severity, and facial severity. Agreement between self-reported numbers of cNFs and investigator-rated numbers based on photographs was “minimal to fair.”
• Female sex, the number of cNFs, severity of cNFs on the face, and globular cNFs were associated with worse QoL (based on Skindex scores); severity of cNFs on the face had the strongest impact on overall QoL (P < .001).
• An increasing number of cNFs and worsening facial severity were strongly correlated with higher emotion subdomain scores.
• A higher number of cNFs, more severe cNFs on the face, and larger cNFs were all slightly associated with increased itch and pain (P < .01).

IN PRACTICE:

“To develop effective therapeutics, meaningful clinical outcomes that are tied with improvement in QoL for persons with NF1 must be clearly defined,” the authors wrote. The results of this study, they added, “suggested the benefit of this crowd-sourced resource by identifying the features of cNFs with the greatest association with QoL and symptoms of pain and itch in persons with NF1, highlighting new intervention strategies and features to target to most improve QoL in NF1.”

SOURCE:

The study was led by Michelle Jade Lin, BS, Stanford University School of Medicine, Redwood City, California, and was published online in JAMA Dermatology.

LIMITATIONS:

The study included only a small number of individuals from racial and ethnic minority groups and did not capture ethnicity information, which could have provided further insights into disease impact across different demographics.

DISCLOSURES:

This study was supported by Johns Hopkins University, Baltimore, and the Bloomberg Family Foundation. Ms. Lin reported support from the Stanford Medical Scholars Research Program. Three authors reported personal fees or grants outside this work. Other authors reported no competing interests.

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.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

Lipedema affects about 11% of cisgender women, according to the Brazilian Society of Angiology and Vascular Surgery. Yet the condition remains wrapped in uncertainties. Despite significant advancements in understanding its physiology, diagnosis, and treatment, more clarity is needed as awareness and diagnoses increase.

At the latest International Congress on Obesity (ICO) in São Paulo, Brazil, Philipp Scherer, PhD, director of the Touchstone Diabetes Center, discussed the complexities of lipedema. “It is an extremely frustrating condition for someone like me, who has spent a lifetime studying functional and dysfunctional adipose tissue. We are trying to understand the physiology of this pathology, but it is challenging, and so far, we have not been able to find a concrete answer,” he noted.

Lipedema is characterized by the abnormal accumulation of subcutaneous adipose tissue, especially in the lower limbs, and almost exclusively affects cisgender women. The reason for this gender disparity is unclear. It could be an intrinsic characteristic of the disease or a result from clinicians’ lack of familiarity with lipedema, which often leads to misdiagnosis as obesity. This misdiagnosis results in fewer men seeking treatment.

Research has predominantly focused on women, and evidence suggests that hormones play a crucial role in the disease’s pathophysiology. Lipedema typically manifests during periods of hormonal changes, such as puberty, pregnancy, menopause, and hormone replacement therapies, reinforcing the idea that hormones significantly influence the condition’s development and progression.
 

Main Symptoms

Jonathan Kartt, CEO of the Lipedema Foundation, emphasized that intense pain in the areas of adipose tissue accumulation is a hallmark symptom of lipedema, setting it apart from obesity. Pain levels can vary widely among patients, ranging from moderate to severe, with unbearable peaks on certain days. Mr. Kartt stressed the importance of recognizing and addressing this often underestimated symptom.

Lipedema is characterized by a bilateral, symmetrical increase in mass compared with the rest of the body. This is commonly distinguished by the “cuff sign,” a separation between normal tissue in the feet and abnormal tissue from the ankle upward. Other frequent symptoms include a feeling of heaviness, discomfort, fatigue, frequent bruising, and tiredness. A notable sign is the presence of subcutaneous nodules with a texture similar to that of rice grains, which are crucial for differentiating lipedema from other conditions. Palpation during anamnesis is essential to identify these nodules and confirm the diagnosis.

“It is crucial to investigate the family history for genetic predisposition. Additionally, it is fundamental to ask whether, even with weight loss, the affected areas retain accumulated fat. Hormonal changes, pain symptoms, and impact on quality of life should also be carefully evaluated,” advised Mr. Kartt.
 

Diagnostic Tools

André Murad, MD, a clinical consultant at the Instituto Lipedema Brazil, has been exploring new diagnostic approaches for lipedema beyond traditional anamnesis. During his presentation at the ICO, he shared studies on the efficacy of imaging exams such as ultrasound, tomography, and MRI in diagnosing the characteristic lipedema-associated increase in subcutaneous tissue.

He also discussed lymphangiography and lymphoscintigraphy, highlighting the use of magnetic resonance lymphangiography to evaluate dilated lymphatic vessels often observed in patients with lipedema. “By injecting contrast into the feet, this technique allows the evaluation of vessels, which are usually dilated, indicating characteristic lymphatic system overload in lipedema. Lymphoscintigraphy is crucial for detecting associated lymphedema, revealing delayed lymphatic flow and asymmetry between limbs in cases of lipedema without lymphedema,” he explained.

Despite the various diagnostic options, Dr. Murad highlighted two highly effective studies. A Brazilian study used ultrasound to establish a cutoff point of 11.7 mm in the pretibial subcutaneous tissue thickness, achieving 96% specificity for diagnosis. Another study emphasized the value of dual-energy x-ray absorptiometry (DXA), which demonstrated 95% sensitivity. This method assesses fat distribution by correlating the amount present in the legs with the total body, providing a cost-effective and accessible option for specialists.

“DXA allows for a precise mathematical evaluation of fat distribution relative to the total body. A ratio of 0.38 in the leg-to-body relationship is a significant indicator of high suspicion of lipedema,” highlighted Dr. Murad. “In clinical practice, many patients self-diagnose with lipedema, but the clinical exam often reveals no disproportion, with the leg-to-body ratio below 0.38 being common in these cases,” he added.
 

Treatment Approaches

Treatments for lipedema are still evolving, with considerable debate about the best approach. While some specialists advocate exclusively for conservative treatment, others recommend combining these methods with surgical interventions, depending on the stage of the disease. The relative novelty of lipedema and the scarcity of robust, long-term studies contribute to the uncertainty around treatment efficacy.

Conservative treatment typically includes compression, lymphatic drainage techniques, and pressure therapy. An active lifestyle and a healthy diet are also recommended. Although these measures do not prevent the accumulation of adipose tissue, they help reduce inflammation and improve quality of life. “Even though the causes of lipedema are not fully known, lifestyle management is essential for controlling symptoms, starting with an anti-inflammatory diet,” emphasized Dr. Murad.

Because insulin promotes lipogenesis, a diet that avoids spikes in glycemic and insulin levels is advisable. Insulin resistance can exacerbate edema formation, so a Mediterranean diet may be beneficial. This diet limits fast-absorbing carbohydrates, such as added sugar, refined grains, and ultraprocessed foods, while promoting complex carbohydrates from whole grains and legumes.

Dr. Murad also presented a study evaluating the potential benefits of a low-carbohydrate, high-fat diet for patients with lipedema. The study demonstrated weight loss, reduced body fat, controlled leg volume, and, notably, pain relief.

For more advanced stages of lipedema, plastic surgery is often considered when conservative approaches do not yield satisfactory results. Some specialists advocate for surgery as an effective way to remove diseased adipose cells and reduce excess fat accumulation, which can improve physical appearance and associated pain. There is a growing consensus that surgical intervention should be performed early, ideally in stage I of IV, to maximize efficacy and prevent disease progression.

Fábio Masato Kamamoto, MD, a plastic surgeon and director of the Instituto Lipedema Brazil, shared insights into surgical treatments for lipedema. He discussed techniques from liposuction to advanced skin retraction and dermolipectomy, crucial for addressing more advanced stages of the condition. “It’s a complex process that demands precision to protect the lymphatic system, especially considering the characteristic nodules of lipedema,” he noted.

Dr. Kamamoto discussed a former patient with stage III lipedema. In the initial stage, he performed liposuction, removing 8 L of fat and 3.4 kg of skin. After 6 months, a follow-up procedure resulted in a total removal of 15 kg. Complementary procedures, such as microneedling, were performed to stimulate collagen production and reduce skin sagging. In addition to cosmetic improvements, the procedure also removed the distinctive lipedema nodules, which Mr. Kartt described as feeling like “rice grains.” Removing these nodules significantly alleviates pain, according to Dr. Kamamoto.

The benefits of surgical treatment for lipedema can be long lasting. Dr. Kamamoto noted that fat tends not to reaccumulate in treated areas, with patients often experiencing lower weight, reduced edema, and decreased pain over time. “While we hope that patients do not regain weight, the benefits of surgery persist even if weight is regained. Therefore, combining conservative and surgical treatments remains a valid and effective approach,” he concluded.

Dr. Scherer highlighted that despite various approaches, there is still no definitive “magic signature” that fully explains lipedema. This lack of clarity directly affects the effectiveness of diagnoses and treatments. He expressed hope that future integration of data from different studies and approaches will lead to the identification of a clinically useful molecular signature. “The true cause of lipedema remains unknown, requiring more speculation, hypothesis formulation, and testing for significant discoveries. This situation is frustrating, as the disease affects many women who lack a clear diagnosis that differentiates them from patients with obesity, as well as evidence-based recommendations,” he concluded.
 

This story was translated from the Medscape Portuguese edition 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.

Lipedema affects about 11% of cisgender women, according to the Brazilian Society of Angiology and Vascular Surgery. Yet the condition remains wrapped in uncertainties. Despite significant advancements in understanding its physiology, diagnosis, and treatment, more clarity is needed as awareness and diagnoses increase.

At the latest International Congress on Obesity (ICO) in São Paulo, Brazil, Philipp Scherer, PhD, director of the Touchstone Diabetes Center, discussed the complexities of lipedema. “It is an extremely frustrating condition for someone like me, who has spent a lifetime studying functional and dysfunctional adipose tissue. We are trying to understand the physiology of this pathology, but it is challenging, and so far, we have not been able to find a concrete answer,” he noted.

Lipedema is characterized by the abnormal accumulation of subcutaneous adipose tissue, especially in the lower limbs, and almost exclusively affects cisgender women. The reason for this gender disparity is unclear. It could be an intrinsic characteristic of the disease or a result from clinicians’ lack of familiarity with lipedema, which often leads to misdiagnosis as obesity. This misdiagnosis results in fewer men seeking treatment.

Research has predominantly focused on women, and evidence suggests that hormones play a crucial role in the disease’s pathophysiology. Lipedema typically manifests during periods of hormonal changes, such as puberty, pregnancy, menopause, and hormone replacement therapies, reinforcing the idea that hormones significantly influence the condition’s development and progression.
 

Main Symptoms

Jonathan Kartt, CEO of the Lipedema Foundation, emphasized that intense pain in the areas of adipose tissue accumulation is a hallmark symptom of lipedema, setting it apart from obesity. Pain levels can vary widely among patients, ranging from moderate to severe, with unbearable peaks on certain days. Mr. Kartt stressed the importance of recognizing and addressing this often underestimated symptom.

Lipedema is characterized by a bilateral, symmetrical increase in mass compared with the rest of the body. This is commonly distinguished by the “cuff sign,” a separation between normal tissue in the feet and abnormal tissue from the ankle upward. Other frequent symptoms include a feeling of heaviness, discomfort, fatigue, frequent bruising, and tiredness. A notable sign is the presence of subcutaneous nodules with a texture similar to that of rice grains, which are crucial for differentiating lipedema from other conditions. Palpation during anamnesis is essential to identify these nodules and confirm the diagnosis.

“It is crucial to investigate the family history for genetic predisposition. Additionally, it is fundamental to ask whether, even with weight loss, the affected areas retain accumulated fat. Hormonal changes, pain symptoms, and impact on quality of life should also be carefully evaluated,” advised Mr. Kartt.
 

Diagnostic Tools

André Murad, MD, a clinical consultant at the Instituto Lipedema Brazil, has been exploring new diagnostic approaches for lipedema beyond traditional anamnesis. During his presentation at the ICO, he shared studies on the efficacy of imaging exams such as ultrasound, tomography, and MRI in diagnosing the characteristic lipedema-associated increase in subcutaneous tissue.

He also discussed lymphangiography and lymphoscintigraphy, highlighting the use of magnetic resonance lymphangiography to evaluate dilated lymphatic vessels often observed in patients with lipedema. “By injecting contrast into the feet, this technique allows the evaluation of vessels, which are usually dilated, indicating characteristic lymphatic system overload in lipedema. Lymphoscintigraphy is crucial for detecting associated lymphedema, revealing delayed lymphatic flow and asymmetry between limbs in cases of lipedema without lymphedema,” he explained.

Despite the various diagnostic options, Dr. Murad highlighted two highly effective studies. A Brazilian study used ultrasound to establish a cutoff point of 11.7 mm in the pretibial subcutaneous tissue thickness, achieving 96% specificity for diagnosis. Another study emphasized the value of dual-energy x-ray absorptiometry (DXA), which demonstrated 95% sensitivity. This method assesses fat distribution by correlating the amount present in the legs with the total body, providing a cost-effective and accessible option for specialists.

“DXA allows for a precise mathematical evaluation of fat distribution relative to the total body. A ratio of 0.38 in the leg-to-body relationship is a significant indicator of high suspicion of lipedema,” highlighted Dr. Murad. “In clinical practice, many patients self-diagnose with lipedema, but the clinical exam often reveals no disproportion, with the leg-to-body ratio below 0.38 being common in these cases,” he added.
 

Treatment Approaches

Treatments for lipedema are still evolving, with considerable debate about the best approach. While some specialists advocate exclusively for conservative treatment, others recommend combining these methods with surgical interventions, depending on the stage of the disease. The relative novelty of lipedema and the scarcity of robust, long-term studies contribute to the uncertainty around treatment efficacy.

Conservative treatment typically includes compression, lymphatic drainage techniques, and pressure therapy. An active lifestyle and a healthy diet are also recommended. Although these measures do not prevent the accumulation of adipose tissue, they help reduce inflammation and improve quality of life. “Even though the causes of lipedema are not fully known, lifestyle management is essential for controlling symptoms, starting with an anti-inflammatory diet,” emphasized Dr. Murad.

Because insulin promotes lipogenesis, a diet that avoids spikes in glycemic and insulin levels is advisable. Insulin resistance can exacerbate edema formation, so a Mediterranean diet may be beneficial. This diet limits fast-absorbing carbohydrates, such as added sugar, refined grains, and ultraprocessed foods, while promoting complex carbohydrates from whole grains and legumes.

Dr. Murad also presented a study evaluating the potential benefits of a low-carbohydrate, high-fat diet for patients with lipedema. The study demonstrated weight loss, reduced body fat, controlled leg volume, and, notably, pain relief.

For more advanced stages of lipedema, plastic surgery is often considered when conservative approaches do not yield satisfactory results. Some specialists advocate for surgery as an effective way to remove diseased adipose cells and reduce excess fat accumulation, which can improve physical appearance and associated pain. There is a growing consensus that surgical intervention should be performed early, ideally in stage I of IV, to maximize efficacy and prevent disease progression.

Fábio Masato Kamamoto, MD, a plastic surgeon and director of the Instituto Lipedema Brazil, shared insights into surgical treatments for lipedema. He discussed techniques from liposuction to advanced skin retraction and dermolipectomy, crucial for addressing more advanced stages of the condition. “It’s a complex process that demands precision to protect the lymphatic system, especially considering the characteristic nodules of lipedema,” he noted.

Dr. Kamamoto discussed a former patient with stage III lipedema. In the initial stage, he performed liposuction, removing 8 L of fat and 3.4 kg of skin. After 6 months, a follow-up procedure resulted in a total removal of 15 kg. Complementary procedures, such as microneedling, were performed to stimulate collagen production and reduce skin sagging. In addition to cosmetic improvements, the procedure also removed the distinctive lipedema nodules, which Mr. Kartt described as feeling like “rice grains.” Removing these nodules significantly alleviates pain, according to Dr. Kamamoto.

The benefits of surgical treatment for lipedema can be long lasting. Dr. Kamamoto noted that fat tends not to reaccumulate in treated areas, with patients often experiencing lower weight, reduced edema, and decreased pain over time. “While we hope that patients do not regain weight, the benefits of surgery persist even if weight is regained. Therefore, combining conservative and surgical treatments remains a valid and effective approach,” he concluded.

Dr. Scherer highlighted that despite various approaches, there is still no definitive “magic signature” that fully explains lipedema. This lack of clarity directly affects the effectiveness of diagnoses and treatments. He expressed hope that future integration of data from different studies and approaches will lead to the identification of a clinically useful molecular signature. “The true cause of lipedema remains unknown, requiring more speculation, hypothesis formulation, and testing for significant discoveries. This situation is frustrating, as the disease affects many women who lack a clear diagnosis that differentiates them from patients with obesity, as well as evidence-based recommendations,” he concluded.
 

This story was translated from the Medscape Portuguese edition 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.

Lipedema affects about 11% of cisgender women, according to the Brazilian Society of Angiology and Vascular Surgery. Yet the condition remains wrapped in uncertainties. Despite significant advancements in understanding its physiology, diagnosis, and treatment, more clarity is needed as awareness and diagnoses increase.

At the latest International Congress on Obesity (ICO) in São Paulo, Brazil, Philipp Scherer, PhD, director of the Touchstone Diabetes Center, discussed the complexities of lipedema. “It is an extremely frustrating condition for someone like me, who has spent a lifetime studying functional and dysfunctional adipose tissue. We are trying to understand the physiology of this pathology, but it is challenging, and so far, we have not been able to find a concrete answer,” he noted.

Lipedema is characterized by the abnormal accumulation of subcutaneous adipose tissue, especially in the lower limbs, and almost exclusively affects cisgender women. The reason for this gender disparity is unclear. It could be an intrinsic characteristic of the disease or a result from clinicians’ lack of familiarity with lipedema, which often leads to misdiagnosis as obesity. This misdiagnosis results in fewer men seeking treatment.

Research has predominantly focused on women, and evidence suggests that hormones play a crucial role in the disease’s pathophysiology. Lipedema typically manifests during periods of hormonal changes, such as puberty, pregnancy, menopause, and hormone replacement therapies, reinforcing the idea that hormones significantly influence the condition’s development and progression.
 

Main Symptoms

Jonathan Kartt, CEO of the Lipedema Foundation, emphasized that intense pain in the areas of adipose tissue accumulation is a hallmark symptom of lipedema, setting it apart from obesity. Pain levels can vary widely among patients, ranging from moderate to severe, with unbearable peaks on certain days. Mr. Kartt stressed the importance of recognizing and addressing this often underestimated symptom.

Lipedema is characterized by a bilateral, symmetrical increase in mass compared with the rest of the body. This is commonly distinguished by the “cuff sign,” a separation between normal tissue in the feet and abnormal tissue from the ankle upward. Other frequent symptoms include a feeling of heaviness, discomfort, fatigue, frequent bruising, and tiredness. A notable sign is the presence of subcutaneous nodules with a texture similar to that of rice grains, which are crucial for differentiating lipedema from other conditions. Palpation during anamnesis is essential to identify these nodules and confirm the diagnosis.

“It is crucial to investigate the family history for genetic predisposition. Additionally, it is fundamental to ask whether, even with weight loss, the affected areas retain accumulated fat. Hormonal changes, pain symptoms, and impact on quality of life should also be carefully evaluated,” advised Mr. Kartt.
 

Diagnostic Tools

André Murad, MD, a clinical consultant at the Instituto Lipedema Brazil, has been exploring new diagnostic approaches for lipedema beyond traditional anamnesis. During his presentation at the ICO, he shared studies on the efficacy of imaging exams such as ultrasound, tomography, and MRI in diagnosing the characteristic lipedema-associated increase in subcutaneous tissue.

He also discussed lymphangiography and lymphoscintigraphy, highlighting the use of magnetic resonance lymphangiography to evaluate dilated lymphatic vessels often observed in patients with lipedema. “By injecting contrast into the feet, this technique allows the evaluation of vessels, which are usually dilated, indicating characteristic lymphatic system overload in lipedema. Lymphoscintigraphy is crucial for detecting associated lymphedema, revealing delayed lymphatic flow and asymmetry between limbs in cases of lipedema without lymphedema,” he explained.

Despite the various diagnostic options, Dr. Murad highlighted two highly effective studies. A Brazilian study used ultrasound to establish a cutoff point of 11.7 mm in the pretibial subcutaneous tissue thickness, achieving 96% specificity for diagnosis. Another study emphasized the value of dual-energy x-ray absorptiometry (DXA), which demonstrated 95% sensitivity. This method assesses fat distribution by correlating the amount present in the legs with the total body, providing a cost-effective and accessible option for specialists.

“DXA allows for a precise mathematical evaluation of fat distribution relative to the total body. A ratio of 0.38 in the leg-to-body relationship is a significant indicator of high suspicion of lipedema,” highlighted Dr. Murad. “In clinical practice, many patients self-diagnose with lipedema, but the clinical exam often reveals no disproportion, with the leg-to-body ratio below 0.38 being common in these cases,” he added.
 

Treatment Approaches

Treatments for lipedema are still evolving, with considerable debate about the best approach. While some specialists advocate exclusively for conservative treatment, others recommend combining these methods with surgical interventions, depending on the stage of the disease. The relative novelty of lipedema and the scarcity of robust, long-term studies contribute to the uncertainty around treatment efficacy.

Conservative treatment typically includes compression, lymphatic drainage techniques, and pressure therapy. An active lifestyle and a healthy diet are also recommended. Although these measures do not prevent the accumulation of adipose tissue, they help reduce inflammation and improve quality of life. “Even though the causes of lipedema are not fully known, lifestyle management is essential for controlling symptoms, starting with an anti-inflammatory diet,” emphasized Dr. Murad.

Because insulin promotes lipogenesis, a diet that avoids spikes in glycemic and insulin levels is advisable. Insulin resistance can exacerbate edema formation, so a Mediterranean diet may be beneficial. This diet limits fast-absorbing carbohydrates, such as added sugar, refined grains, and ultraprocessed foods, while promoting complex carbohydrates from whole grains and legumes.

Dr. Murad also presented a study evaluating the potential benefits of a low-carbohydrate, high-fat diet for patients with lipedema. The study demonstrated weight loss, reduced body fat, controlled leg volume, and, notably, pain relief.

For more advanced stages of lipedema, plastic surgery is often considered when conservative approaches do not yield satisfactory results. Some specialists advocate for surgery as an effective way to remove diseased adipose cells and reduce excess fat accumulation, which can improve physical appearance and associated pain. There is a growing consensus that surgical intervention should be performed early, ideally in stage I of IV, to maximize efficacy and prevent disease progression.

Fábio Masato Kamamoto, MD, a plastic surgeon and director of the Instituto Lipedema Brazil, shared insights into surgical treatments for lipedema. He discussed techniques from liposuction to advanced skin retraction and dermolipectomy, crucial for addressing more advanced stages of the condition. “It’s a complex process that demands precision to protect the lymphatic system, especially considering the characteristic nodules of lipedema,” he noted.

Dr. Kamamoto discussed a former patient with stage III lipedema. In the initial stage, he performed liposuction, removing 8 L of fat and 3.4 kg of skin. After 6 months, a follow-up procedure resulted in a total removal of 15 kg. Complementary procedures, such as microneedling, were performed to stimulate collagen production and reduce skin sagging. In addition to cosmetic improvements, the procedure also removed the distinctive lipedema nodules, which Mr. Kartt described as feeling like “rice grains.” Removing these nodules significantly alleviates pain, according to Dr. Kamamoto.

The benefits of surgical treatment for lipedema can be long lasting. Dr. Kamamoto noted that fat tends not to reaccumulate in treated areas, with patients often experiencing lower weight, reduced edema, and decreased pain over time. “While we hope that patients do not regain weight, the benefits of surgery persist even if weight is regained. Therefore, combining conservative and surgical treatments remains a valid and effective approach,” he concluded.

Dr. Scherer highlighted that despite various approaches, there is still no definitive “magic signature” that fully explains lipedema. This lack of clarity directly affects the effectiveness of diagnoses and treatments. He expressed hope that future integration of data from different studies and approaches will lead to the identification of a clinically useful molecular signature. “The true cause of lipedema remains unknown, requiring more speculation, hypothesis formulation, and testing for significant discoveries. This situation is frustrating, as the disease affects many women who lack a clear diagnosis that differentiates them from patients with obesity, as well as evidence-based recommendations,” he concluded.
 

This story was translated from the Medscape Portuguese edition 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:

The incidence of dermatofibrosarcoma protuberans (DFSP) is twice as high in Black individuals as in White individuals, according to a study that also found that larger tumor size and older age were associated with survival outcomes.

METHODOLOGY:

• Researchers used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry from 2000 through 2018 to provide a comprehensive report on the incidence of DFSP, a rare, low-grade cutaneous soft tissue sarcoma, and factors associated with metastatic progression, overall survival (OS), and cancer-specific survival.
• A total of 7748 patients (mean age, 43.5 years; 53.3% women; 52% non-Hispanic White) were diagnosed with histologically confirmed DFSP of the skin and connective tissue and were included in the study.
• DFSP incidence was reported as cases per million person-years and age-adjusted to the 2000 US Standard Population, and factors influencing metastasis were assessed.

TAKEAWAY:

• The overall DFSP incidence rate was 6.25 cases per million person-years, with a higher incidence in Black individuals than in White individuals (8.74 vs 4.53).
• The 5-year OS rate was 95.8%. Older age (≥ 60 years; hazard ratio [HR], 6.66), male gender assigned at birth (HR, 1.79), and larger tumor size (≥ 3 cm; HR, 2.02) were associated with poorer OS (P < .001 for all).
• The 1-year and 5-year DFSP-specific survival rates were 99.9% and 99.2%, respectively. Older age (HR, 3.47; P < .001) and larger tumor size (≥ 3 cm; HR, 5.34; P = .002) were associated with significantly worse cancer-specific survival.
• Large tumor size (odds ratio [OR], 2.24) and DFSP located on the head and neck (OR, 4.88), or genitalia (OR, 3.16) were significantly associated with increased metastasis risk. Higher socioeconomic status was linked to a lower risk for metastasis.

IN PRACTICE:

“Our findings highlight the increased incidence rates of DFSP among Black patients. We demonstrate the interplay between patient demographics and clinical factors in influencing DFSP metastasis, OS, and cancer-specific survival,” the authors wrote. The results, they added, “may be useful for further evaluation of proposed causes, which will ultimately lead to further understanding and prevention of this disease.”
 

SOURCE:

The study was led by Jalal Maghfour, MD, Department of Dermatology, Henry Ford Health, Detroit, and was published online on June 20 in the Journal of the American Academy of Dermatology.
 

LIMITATIONS:

Details on specific cases in the SEER registry are limited. For 1752 patients, tumor size was not included, increasing the risk for misclassification bias. Because specific pathology reports were not available, the analysis did not address histologic grade.
 

DISCLOSURES:

The study did not receive any funding support. The authors declared no conflicts of interest.
 

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 appeared on Medscape.com.

TOPLINE:

The incidence of dermatofibrosarcoma protuberans (DFSP) is twice as high in Black individuals as in White individuals, according to a study that also found that larger tumor size and older age were associated with survival outcomes.

METHODOLOGY:

• Researchers used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry from 2000 through 2018 to provide a comprehensive report on the incidence of DFSP, a rare, low-grade cutaneous soft tissue sarcoma, and factors associated with metastatic progression, overall survival (OS), and cancer-specific survival.
• A total of 7748 patients (mean age, 43.5 years; 53.3% women; 52% non-Hispanic White) were diagnosed with histologically confirmed DFSP of the skin and connective tissue and were included in the study.
• DFSP incidence was reported as cases per million person-years and age-adjusted to the 2000 US Standard Population, and factors influencing metastasis were assessed.

TAKEAWAY:

• The overall DFSP incidence rate was 6.25 cases per million person-years, with a higher incidence in Black individuals than in White individuals (8.74 vs 4.53).
• The 5-year OS rate was 95.8%. Older age (≥ 60 years; hazard ratio [HR], 6.66), male gender assigned at birth (HR, 1.79), and larger tumor size (≥ 3 cm; HR, 2.02) were associated with poorer OS (P < .001 for all).
• The 1-year and 5-year DFSP-specific survival rates were 99.9% and 99.2%, respectively. Older age (HR, 3.47; P < .001) and larger tumor size (≥ 3 cm; HR, 5.34; P = .002) were associated with significantly worse cancer-specific survival.
• Large tumor size (odds ratio [OR], 2.24) and DFSP located on the head and neck (OR, 4.88), or genitalia (OR, 3.16) were significantly associated with increased metastasis risk. Higher socioeconomic status was linked to a lower risk for metastasis.

IN PRACTICE:

“Our findings highlight the increased incidence rates of DFSP among Black patients. We demonstrate the interplay between patient demographics and clinical factors in influencing DFSP metastasis, OS, and cancer-specific survival,” the authors wrote. The results, they added, “may be useful for further evaluation of proposed causes, which will ultimately lead to further understanding and prevention of this disease.”
 

SOURCE:

The study was led by Jalal Maghfour, MD, Department of Dermatology, Henry Ford Health, Detroit, and was published online on June 20 in the Journal of the American Academy of Dermatology.
 

LIMITATIONS:

Details on specific cases in the SEER registry are limited. For 1752 patients, tumor size was not included, increasing the risk for misclassification bias. Because specific pathology reports were not available, the analysis did not address histologic grade.
 

DISCLOSURES:

The study did not receive any funding support. The authors declared no conflicts of interest.
 

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 appeared on Medscape.com.

TOPLINE:

The incidence of dermatofibrosarcoma protuberans (DFSP) is twice as high in Black individuals as in White individuals, according to a study that also found that larger tumor size and older age were associated with survival outcomes.

METHODOLOGY:

• Researchers used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry from 2000 through 2018 to provide a comprehensive report on the incidence of DFSP, a rare, low-grade cutaneous soft tissue sarcoma, and factors associated with metastatic progression, overall survival (OS), and cancer-specific survival.
• A total of 7748 patients (mean age, 43.5 years; 53.3% women; 52% non-Hispanic White) were diagnosed with histologically confirmed DFSP of the skin and connective tissue and were included in the study.
• DFSP incidence was reported as cases per million person-years and age-adjusted to the 2000 US Standard Population, and factors influencing metastasis were assessed.

TAKEAWAY:

• The overall DFSP incidence rate was 6.25 cases per million person-years, with a higher incidence in Black individuals than in White individuals (8.74 vs 4.53).
• The 5-year OS rate was 95.8%. Older age (≥ 60 years; hazard ratio [HR], 6.66), male gender assigned at birth (HR, 1.79), and larger tumor size (≥ 3 cm; HR, 2.02) were associated with poorer OS (P < .001 for all).
• The 1-year and 5-year DFSP-specific survival rates were 99.9% and 99.2%, respectively. Older age (HR, 3.47; P < .001) and larger tumor size (≥ 3 cm; HR, 5.34; P = .002) were associated with significantly worse cancer-specific survival.
• Large tumor size (odds ratio [OR], 2.24) and DFSP located on the head and neck (OR, 4.88), or genitalia (OR, 3.16) were significantly associated with increased metastasis risk. Higher socioeconomic status was linked to a lower risk for metastasis.

IN PRACTICE:

“Our findings highlight the increased incidence rates of DFSP among Black patients. We demonstrate the interplay between patient demographics and clinical factors in influencing DFSP metastasis, OS, and cancer-specific survival,” the authors wrote. The results, they added, “may be useful for further evaluation of proposed causes, which will ultimately lead to further understanding and prevention of this disease.”
 

SOURCE:

The study was led by Jalal Maghfour, MD, Department of Dermatology, Henry Ford Health, Detroit, and was published online on June 20 in the Journal of the American Academy of Dermatology.
 

LIMITATIONS:

Details on specific cases in the SEER registry are limited. For 1752 patients, tumor size was not included, increasing the risk for misclassification bias. Because specific pathology reports were not available, the analysis did not address histologic grade.
 

DISCLOSURES:

The study did not receive any funding support. The authors declared no conflicts of interest.
 

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 appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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