Autoimmune Diseases

TOPLINE:

A greater proportion of patients with active systemic lupus erythematosus (SLE) treated with belimumab plus standard therapy achieved the newest definitions for remission and low disease activity compared with those treated with placebo plus standard therapy, with benefits observed as early as week 28 for remission and week 8 for disease activity, according to pooled results from five clinical trials.

METHODOLOGY:

• Researchers conducted an integrated post hoc analysis of five randomized phase 3 clinical trials to evaluate the attainment of remission and low disease activity in adult patients with active, autoantibody-positive SLE.
• A total of 3086 patients (median age, 36 years; 94% women) were randomly assigned to receive standard therapy with intravenous belimumab 10 mg/kg monthly or subcutaneous belimumab 200 mg weekly (n = 1869) or placebo (n = 1217).
• The proportion of patients who achieved definitions of remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) by visit up to week 52 was assessed.
• The analysis also evaluated the time taken to achieve sustained (at least two consecutive visits) and maintained (up to week 52) DORIS remission and LLDAS.

TAKEAWAY:

• At week 52, a higher proportion of patients receiving belimumab vs placebo achieved DORIS remission (8% vs 6%; risk ratio [RR], 1.51; P = .0055) and LLDAS (17% vs 10%; RR, 1.74; P < .0001).
• The earliest observed significant benefit of belimumab over placebo in patients with a higher baseline disease activity was at week 20 for DORIS remission (RR, 2.09; P = .043) and at week 16 for LLDAS (RR, 1.46; P = .034), with both maintained through week 52.
• The proportion of patients who attained DORIS remission and LLDAS as early as week 28 and week 8, respectively, was higher in the belimumab group than in the placebo group, with both maintained through week 52.
• Patients on belimumab were more likely to have a sustained and maintained DORIS remission (hazard ratio [HR], 1.53; P = .013) and LLDAS (HR, 1.79; P < .0001) at any timepoint.

IN PRACTICE:

“The data clearly support that belimumab is a valuable addition toward accomplishing and maintaining remission or LLDAS,” George Bertsias, MD, PhD, University of Crete Medical School, Heraklion, Greece, and Jinoos Yazdany, MD, University of California San Francisco, wrote in a related comment.

SOURCE:

This study, led by Ioannis Parodis, MD, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, was published online on August 26, 2024, in The Lancet Rheumatology.

LIMITATIONS: 

Due to the post hoc nature of the analysis, the trials were not specifically designed to have adequate statistical power to demonstrate the difference between patients who did or did not achieve DORIS remission or LLDAS. The analysis was limited to patients who met the eligibility criteria, and the outcomes are not generalizable to populations outside a clinical trial setting. The study population had high disease activity, which made it challenging to attain the treatment targets.

DISCLOSURES:

The five trials included in this analysis were funded by GSK. The study was supported by the Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, the Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet. Some authors reported receiving grants, speaker honoraria, or consulting fees from various pharmaceutical companies. Some authors reported being employees and owning stocks and shares of GSK.
 

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:

A greater proportion of patients with active systemic lupus erythematosus (SLE) treated with belimumab plus standard therapy achieved the newest definitions for remission and low disease activity compared with those treated with placebo plus standard therapy, with benefits observed as early as week 28 for remission and week 8 for disease activity, according to pooled results from five clinical trials.

METHODOLOGY:

• Researchers conducted an integrated post hoc analysis of five randomized phase 3 clinical trials to evaluate the attainment of remission and low disease activity in adult patients with active, autoantibody-positive SLE.
• A total of 3086 patients (median age, 36 years; 94% women) were randomly assigned to receive standard therapy with intravenous belimumab 10 mg/kg monthly or subcutaneous belimumab 200 mg weekly (n = 1869) or placebo (n = 1217).
• The proportion of patients who achieved definitions of remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) by visit up to week 52 was assessed.
• The analysis also evaluated the time taken to achieve sustained (at least two consecutive visits) and maintained (up to week 52) DORIS remission and LLDAS.

TAKEAWAY:

• At week 52, a higher proportion of patients receiving belimumab vs placebo achieved DORIS remission (8% vs 6%; risk ratio [RR], 1.51; P = .0055) and LLDAS (17% vs 10%; RR, 1.74; P < .0001).
• The earliest observed significant benefit of belimumab over placebo in patients with a higher baseline disease activity was at week 20 for DORIS remission (RR, 2.09; P = .043) and at week 16 for LLDAS (RR, 1.46; P = .034), with both maintained through week 52.
• The proportion of patients who attained DORIS remission and LLDAS as early as week 28 and week 8, respectively, was higher in the belimumab group than in the placebo group, with both maintained through week 52.
• Patients on belimumab were more likely to have a sustained and maintained DORIS remission (hazard ratio [HR], 1.53; P = .013) and LLDAS (HR, 1.79; P < .0001) at any timepoint.

IN PRACTICE:

“The data clearly support that belimumab is a valuable addition toward accomplishing and maintaining remission or LLDAS,” George Bertsias, MD, PhD, University of Crete Medical School, Heraklion, Greece, and Jinoos Yazdany, MD, University of California San Francisco, wrote in a related comment.

SOURCE:

This study, led by Ioannis Parodis, MD, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, was published online on August 26, 2024, in The Lancet Rheumatology.

LIMITATIONS: 

Due to the post hoc nature of the analysis, the trials were not specifically designed to have adequate statistical power to demonstrate the difference between patients who did or did not achieve DORIS remission or LLDAS. The analysis was limited to patients who met the eligibility criteria, and the outcomes are not generalizable to populations outside a clinical trial setting. The study population had high disease activity, which made it challenging to attain the treatment targets.

DISCLOSURES:

The five trials included in this analysis were funded by GSK. The study was supported by the Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, the Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet. Some authors reported receiving grants, speaker honoraria, or consulting fees from various pharmaceutical companies. Some authors reported being employees and owning stocks and shares of GSK.
 

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:

A greater proportion of patients with active systemic lupus erythematosus (SLE) treated with belimumab plus standard therapy achieved the newest definitions for remission and low disease activity compared with those treated with placebo plus standard therapy, with benefits observed as early as week 28 for remission and week 8 for disease activity, according to pooled results from five clinical trials.

METHODOLOGY:

• Researchers conducted an integrated post hoc analysis of five randomized phase 3 clinical trials to evaluate the attainment of remission and low disease activity in adult patients with active, autoantibody-positive SLE.
• A total of 3086 patients (median age, 36 years; 94% women) were randomly assigned to receive standard therapy with intravenous belimumab 10 mg/kg monthly or subcutaneous belimumab 200 mg weekly (n = 1869) or placebo (n = 1217).
• The proportion of patients who achieved definitions of remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) by visit up to week 52 was assessed.
• The analysis also evaluated the time taken to achieve sustained (at least two consecutive visits) and maintained (up to week 52) DORIS remission and LLDAS.

TAKEAWAY:

• At week 52, a higher proportion of patients receiving belimumab vs placebo achieved DORIS remission (8% vs 6%; risk ratio [RR], 1.51; P = .0055) and LLDAS (17% vs 10%; RR, 1.74; P < .0001).
• The earliest observed significant benefit of belimumab over placebo in patients with a higher baseline disease activity was at week 20 for DORIS remission (RR, 2.09; P = .043) and at week 16 for LLDAS (RR, 1.46; P = .034), with both maintained through week 52.
• The proportion of patients who attained DORIS remission and LLDAS as early as week 28 and week 8, respectively, was higher in the belimumab group than in the placebo group, with both maintained through week 52.
• Patients on belimumab were more likely to have a sustained and maintained DORIS remission (hazard ratio [HR], 1.53; P = .013) and LLDAS (HR, 1.79; P < .0001) at any timepoint.

IN PRACTICE:

“The data clearly support that belimumab is a valuable addition toward accomplishing and maintaining remission or LLDAS,” George Bertsias, MD, PhD, University of Crete Medical School, Heraklion, Greece, and Jinoos Yazdany, MD, University of California San Francisco, wrote in a related comment.

SOURCE:

This study, led by Ioannis Parodis, MD, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, was published online on August 26, 2024, in The Lancet Rheumatology.

LIMITATIONS: 

Due to the post hoc nature of the analysis, the trials were not specifically designed to have adequate statistical power to demonstrate the difference between patients who did or did not achieve DORIS remission or LLDAS. The analysis was limited to patients who met the eligibility criteria, and the outcomes are not generalizable to populations outside a clinical trial setting. The study population had high disease activity, which made it challenging to attain the treatment targets.

DISCLOSURES:

The five trials included in this analysis were funded by GSK. The study was supported by the Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, the Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet. Some authors reported receiving grants, speaker honoraria, or consulting fees from various pharmaceutical companies. Some authors reported being employees and owning stocks and shares of GSK.
 

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:

Current use of hydroxychloroquine is associated with a lower risk for myocardial infarction (MI), stroke, and other thromboembolic events in patients with systemic lupus erythematosus (SLE). This protective effect diminishes after discontinuation of hydroxychloroquine treatment.

METHODOLOGY:

• Researchers used a nested case-control design to evaluate the association between exposure to hydroxychloroquine and the risk for cardiovascular events in patients with SLE.
• They included 52,883 adults with SLE (mean age, 44.23 years; 86.6% women) identified from the National System of Health Databases, which includes 99% of the French population.
• Among these, 1981 individuals with composite cardiovascular conditions were matched with 16,892 control individuals without cardiovascular conditions.
• Patients were categorized on the basis of hydroxychloroquine exposure into current users (last exposure within 90 days before a cardiovascular event), remote users (91-365 days before), and nonusers (no exposure within 365 days).
• The study outcomes included a composite of cardiovascular events, including MI, stroke (including transient ischemic attack), and other thromboembolic events such as phlebitis, thrombophlebitis, venous thrombosis, venous thromboembolism, and pulmonary embolism.

TAKEAWAY:

• Current hydroxychloroquine users had lower odds of experiencing a composite cardiovascular outcome than nonusers (adjusted odds ratio [aOR], 0.63; 95% CI, 0.57-0.70).
• The odds of MI (aOR, 0.72; 95% CI, 0.60-0.87), stroke (aOR, 0.71; 95% CI, 0.61-0.83), and other thromboembolic events (aOR, 0.58; 95% CI, 0.48-0.69) were also lower among current users than among nonusers.
• No significant association was found for remote hydroxychloroquine exposure and the risk for composite cardiovascular events, MI, stroke, and other thromboembolic events.

IN PRACTICE:

“These findings support the protective association of hydroxychloroquine against CV [cardiovascular] events and underscore the importance of continuous hydroxychloroquine therapy for patients diagnosed with SLE,” the authors wrote.

SOURCE:

The study was led by Lamiae Grimaldi-Bensouda, PharmD, PhD, Department of Pharmacology, Hospital Group Paris-Saclay, Assistance Publique-Hôpitaux de Paris, France. It was published online on August 30, 2024, in JAMA Network Open.

LIMITATIONS:

The observational nature of the study may have introduced confounding. Current hydroxychloroquine users were younger than nonusers, with an average age difference of almost 5 years. Current hydroxychloroquine users had a twofold longer duration of onset of SLE and had a higher prevalence of chronic kidney disease compared with nonusers.

DISCLOSURES:

This study was funded by the Banque pour l’Investissement, Deeptech. Some authors declared having financial ties with various institutions and companies outside of the current study.
 

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:

Current use of hydroxychloroquine is associated with a lower risk for myocardial infarction (MI), stroke, and other thromboembolic events in patients with systemic lupus erythematosus (SLE). This protective effect diminishes after discontinuation of hydroxychloroquine treatment.

METHODOLOGY:

• Researchers used a nested case-control design to evaluate the association between exposure to hydroxychloroquine and the risk for cardiovascular events in patients with SLE.
• They included 52,883 adults with SLE (mean age, 44.23 years; 86.6% women) identified from the National System of Health Databases, which includes 99% of the French population.
• Among these, 1981 individuals with composite cardiovascular conditions were matched with 16,892 control individuals without cardiovascular conditions.
• Patients were categorized on the basis of hydroxychloroquine exposure into current users (last exposure within 90 days before a cardiovascular event), remote users (91-365 days before), and nonusers (no exposure within 365 days).
• The study outcomes included a composite of cardiovascular events, including MI, stroke (including transient ischemic attack), and other thromboembolic events such as phlebitis, thrombophlebitis, venous thrombosis, venous thromboembolism, and pulmonary embolism.

TAKEAWAY:

• Current hydroxychloroquine users had lower odds of experiencing a composite cardiovascular outcome than nonusers (adjusted odds ratio [aOR], 0.63; 95% CI, 0.57-0.70).
• The odds of MI (aOR, 0.72; 95% CI, 0.60-0.87), stroke (aOR, 0.71; 95% CI, 0.61-0.83), and other thromboembolic events (aOR, 0.58; 95% CI, 0.48-0.69) were also lower among current users than among nonusers.
• No significant association was found for remote hydroxychloroquine exposure and the risk for composite cardiovascular events, MI, stroke, and other thromboembolic events.

IN PRACTICE:

“These findings support the protective association of hydroxychloroquine against CV [cardiovascular] events and underscore the importance of continuous hydroxychloroquine therapy for patients diagnosed with SLE,” the authors wrote.

SOURCE:

The study was led by Lamiae Grimaldi-Bensouda, PharmD, PhD, Department of Pharmacology, Hospital Group Paris-Saclay, Assistance Publique-Hôpitaux de Paris, France. It was published online on August 30, 2024, in JAMA Network Open.

LIMITATIONS:

The observational nature of the study may have introduced confounding. Current hydroxychloroquine users were younger than nonusers, with an average age difference of almost 5 years. Current hydroxychloroquine users had a twofold longer duration of onset of SLE and had a higher prevalence of chronic kidney disease compared with nonusers.

DISCLOSURES:

This study was funded by the Banque pour l’Investissement, Deeptech. Some authors declared having financial ties with various institutions and companies outside of the current study.
 

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:

Current use of hydroxychloroquine is associated with a lower risk for myocardial infarction (MI), stroke, and other thromboembolic events in patients with systemic lupus erythematosus (SLE). This protective effect diminishes after discontinuation of hydroxychloroquine treatment.

METHODOLOGY:

• Researchers used a nested case-control design to evaluate the association between exposure to hydroxychloroquine and the risk for cardiovascular events in patients with SLE.
• They included 52,883 adults with SLE (mean age, 44.23 years; 86.6% women) identified from the National System of Health Databases, which includes 99% of the French population.
• Among these, 1981 individuals with composite cardiovascular conditions were matched with 16,892 control individuals without cardiovascular conditions.
• Patients were categorized on the basis of hydroxychloroquine exposure into current users (last exposure within 90 days before a cardiovascular event), remote users (91-365 days before), and nonusers (no exposure within 365 days).
• The study outcomes included a composite of cardiovascular events, including MI, stroke (including transient ischemic attack), and other thromboembolic events such as phlebitis, thrombophlebitis, venous thrombosis, venous thromboembolism, and pulmonary embolism.

TAKEAWAY:

• Current hydroxychloroquine users had lower odds of experiencing a composite cardiovascular outcome than nonusers (adjusted odds ratio [aOR], 0.63; 95% CI, 0.57-0.70).
• The odds of MI (aOR, 0.72; 95% CI, 0.60-0.87), stroke (aOR, 0.71; 95% CI, 0.61-0.83), and other thromboembolic events (aOR, 0.58; 95% CI, 0.48-0.69) were also lower among current users than among nonusers.
• No significant association was found for remote hydroxychloroquine exposure and the risk for composite cardiovascular events, MI, stroke, and other thromboembolic events.

IN PRACTICE:

“These findings support the protective association of hydroxychloroquine against CV [cardiovascular] events and underscore the importance of continuous hydroxychloroquine therapy for patients diagnosed with SLE,” the authors wrote.

SOURCE:

The study was led by Lamiae Grimaldi-Bensouda, PharmD, PhD, Department of Pharmacology, Hospital Group Paris-Saclay, Assistance Publique-Hôpitaux de Paris, France. It was published online on August 30, 2024, in JAMA Network Open.

LIMITATIONS:

The observational nature of the study may have introduced confounding. Current hydroxychloroquine users were younger than nonusers, with an average age difference of almost 5 years. Current hydroxychloroquine users had a twofold longer duration of onset of SLE and had a higher prevalence of chronic kidney disease compared with nonusers.

DISCLOSURES:

This study was funded by the Banque pour l’Investissement, Deeptech. Some authors declared having financial ties with various institutions and companies outside of the current study.
 

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.

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

TOPLINE:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

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:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

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:

In systemic sclerosis, Raynaud phenomenon is more severe at both high and low temperature extremes, according to new research.

BACKGROUND:

• Raynaud phenomenon, a condition that causes decreased blood flow to extremities, occurs in about 95% of individuals with systemic sclerosis.
• Episodes of Raynaud phenomenon can be triggered by cold exposure and ambient temperature changes.
• In severe cases, it can cause permanent damage to tissues of the fingers and toes.

METHODOLOGY:

• Researchers analyzed data from 2243 participants with Raynaud phenomenon secondary to systemic sclerosis from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
• Participants completed past-week Raynaud phenomenon severity assessments using a 0-10 numerical rating scale at enrollment and every 3 months.
• The study included data from 20,233 Raynaud phenomenon severity assessments between April 15, 2014, and August 1, 2023.
• Researchers used average daily temperature from a weather site close to the participant’s recruiting center and mapped these ambient temperature changes to Raynaud’s phenomenon outcomes.

TAKEAWAY:

• Raynaud’s phenomenon severity was highest at –25 °C (–13 °F), with assessment scores at 6.8 points out of 10.0, and lowest at 25 °C (77 °F), with scores at 2.6.
• Severity scores increased again at temperatures above 35 °C (95 °F), reaching a high of 5.6 out of 10 at 40 °C (104 °F).
• This spike at higher temperatures is presumably due to air conditioning, the authors said.
• In an accompanying commentary, Cutolo et al. posited that increased sweating and hypotension could also lead to a relative hypovolemic state in patients, causing Raynaud-like symptoms.

IN PRACTICE:

“Temperature-related variations in Raynaud’s phenomenon severity scores should be considered in clinical trials to account for normal within-season temperature fluctuations, enhancing the accuracy of treatment outcomes,” wrote Cutolo and colleagues in their commentary.

SOURCE:

The study was led by Gabrielle Virgili-Gervais, MSc, McGill University Health Centre in Montreal, Quebec, Canada. It was published online on August 28 in The Lancet Rheumatology. The accompanying commentary, also published on August 28, was authored by Maurizio Cutolo, MD, and Elvis Hysa, MD, both of University of Genova, Italy, as well as Vanessa Smith, MD, PhD, of Ghent University in Ghent, Belgium.

LIMITATIONS:

The lower number of assessments at extreme temperatures (–25 °C and 40 °C) may affect the robustness of the findings at these ranges. The study did not account for vasodilator use, which could influence participants’ response to temperature. The study also did not account for other potential confounding factors such as sex, smoking status, psychosocial factors, and comorbid conditions like cardiovascular disease.

DISCLOSURES:

A variety of scleroderma-related patient advocacy groups helped to fund research on the SPIN cohort, in addition to the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University. Two authors reported having financial ties with pharmaceutical companies. Dr. Cutolo, Dr. Smith, and Dr. Hysa had no disclosures.

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:

Systemic sclerosis sine scleroderma (ssSSc) affects nearly 10% of patients with systemic sclerosis (SSc), with substantial internal organ involvement. Despite lacking skin fibrosis, patients with ssSSc are at a risk for interstitial lung disease, pulmonary arterial hypertension, and cardiac dysfunction.

METHODOLOGY:

• Driven by a fatal case of ssSSc with cardiac involvement, researchers aimed to evaluate its prevalence, severity, and prognosis.
• They conducted a systematic literature and qualitative synthesis of 35 studies on SSc cohorts from databases published between 1976 and 2023 that comprised data on the prevalence of SSc with or without organ involvement.
• A total of 25,455 patients with SSc were included, with 2437 identified as having ssSSc.
• Studies used various classification criteria for SSc, including the 1980 American Rheumatism Association criteria, 2001 LeRoy and Medsger criteria, and 2013 American College of Rheumatology/European League Against Rheumatism criteria, while ssSSc was classified on the basis of the definitions provided by Rodnan and Fennell and also Poormoghim.
• The analysis focused on ssSSc prevalence, reclassification rates, and internal organ involvement, including interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac dysfunction.

TAKEAWAY:

• The overall mean prevalence of ssSSc was 9.6%, with a range of 0%-22.9% across different studies.
• Reclassification rates of ssSSc into limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) varied substantially, with some studies reporting rates as high as 27.8% over a 4-year follow-up period.
• The mean frequency of internal organ involvement in patients with ssSSc was 46% for interstitial lung disease, 15% for pulmonary arterial hypertension, 5% for scleroderma renal crisis, and 26.5% for cardiac dysfunction — mainly diastolic dysfunction.
• The survival rates in patients with ssSSc were similar to those with lcSSc and better than those with dcSSc.

IN PRACTICE:

“The results presented herein suggest a slightly more severe yet similar clinical picture of ssSSc compared to lcSSc [limited cutaneous SSc], while dcSSc [diffuse cutaneous SSc] remains the most severe disease form,” the authors wrote. “Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered,” they further added.

SOURCE:

The study was led by Anastasios Makris, MD, First Department of Propaedeutic & Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. It was published online on August 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The variability in the classification criteria across different studies may affect the comparability of results. The included studies lacked data on cardiac MRI, restricting the identification of myocardial fibrosis patterns and characterization of cardiac disease activity.

DISCLOSURES:

The study did not receive any specific funding. Some authors disclosed having a consultancy relationship, serving as speakers, and receiving funding for research from multiple companies. One author reported having a patent and being a cofounder of CITUS AG.

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:

Systemic sclerosis sine scleroderma (ssSSc) affects nearly 10% of patients with systemic sclerosis (SSc), with substantial internal organ involvement. Despite lacking skin fibrosis, patients with ssSSc are at a risk for interstitial lung disease, pulmonary arterial hypertension, and cardiac dysfunction.

METHODOLOGY:

• Driven by a fatal case of ssSSc with cardiac involvement, researchers aimed to evaluate its prevalence, severity, and prognosis.
• They conducted a systematic literature and qualitative synthesis of 35 studies on SSc cohorts from databases published between 1976 and 2023 that comprised data on the prevalence of SSc with or without organ involvement.
• A total of 25,455 patients with SSc were included, with 2437 identified as having ssSSc.
• Studies used various classification criteria for SSc, including the 1980 American Rheumatism Association criteria, 2001 LeRoy and Medsger criteria, and 2013 American College of Rheumatology/European League Against Rheumatism criteria, while ssSSc was classified on the basis of the definitions provided by Rodnan and Fennell and also Poormoghim.
• The analysis focused on ssSSc prevalence, reclassification rates, and internal organ involvement, including interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac dysfunction.

TAKEAWAY:

• The overall mean prevalence of ssSSc was 9.6%, with a range of 0%-22.9% across different studies.
• Reclassification rates of ssSSc into limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) varied substantially, with some studies reporting rates as high as 27.8% over a 4-year follow-up period.
• The mean frequency of internal organ involvement in patients with ssSSc was 46% for interstitial lung disease, 15% for pulmonary arterial hypertension, 5% for scleroderma renal crisis, and 26.5% for cardiac dysfunction — mainly diastolic dysfunction.
• The survival rates in patients with ssSSc were similar to those with lcSSc and better than those with dcSSc.

IN PRACTICE:

“The results presented herein suggest a slightly more severe yet similar clinical picture of ssSSc compared to lcSSc [limited cutaneous SSc], while dcSSc [diffuse cutaneous SSc] remains the most severe disease form,” the authors wrote. “Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered,” they further added.

SOURCE:

The study was led by Anastasios Makris, MD, First Department of Propaedeutic & Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. It was published online on August 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The variability in the classification criteria across different studies may affect the comparability of results. The included studies lacked data on cardiac MRI, restricting the identification of myocardial fibrosis patterns and characterization of cardiac disease activity.

DISCLOSURES:

The study did not receive any specific funding. Some authors disclosed having a consultancy relationship, serving as speakers, and receiving funding for research from multiple companies. One author reported having a patent and being a cofounder of CITUS AG.

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:

Systemic sclerosis sine scleroderma (ssSSc) affects nearly 10% of patients with systemic sclerosis (SSc), with substantial internal organ involvement. Despite lacking skin fibrosis, patients with ssSSc are at a risk for interstitial lung disease, pulmonary arterial hypertension, and cardiac dysfunction.

METHODOLOGY:

• Driven by a fatal case of ssSSc with cardiac involvement, researchers aimed to evaluate its prevalence, severity, and prognosis.
• They conducted a systematic literature and qualitative synthesis of 35 studies on SSc cohorts from databases published between 1976 and 2023 that comprised data on the prevalence of SSc with or without organ involvement.
• A total of 25,455 patients with SSc were included, with 2437 identified as having ssSSc.
• Studies used various classification criteria for SSc, including the 1980 American Rheumatism Association criteria, 2001 LeRoy and Medsger criteria, and 2013 American College of Rheumatology/European League Against Rheumatism criteria, while ssSSc was classified on the basis of the definitions provided by Rodnan and Fennell and also Poormoghim.
• The analysis focused on ssSSc prevalence, reclassification rates, and internal organ involvement, including interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac dysfunction.

TAKEAWAY:

• The overall mean prevalence of ssSSc was 9.6%, with a range of 0%-22.9% across different studies.
• Reclassification rates of ssSSc into limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) varied substantially, with some studies reporting rates as high as 27.8% over a 4-year follow-up period.
• The mean frequency of internal organ involvement in patients with ssSSc was 46% for interstitial lung disease, 15% for pulmonary arterial hypertension, 5% for scleroderma renal crisis, and 26.5% for cardiac dysfunction — mainly diastolic dysfunction.
• The survival rates in patients with ssSSc were similar to those with lcSSc and better than those with dcSSc.

IN PRACTICE:

“The results presented herein suggest a slightly more severe yet similar clinical picture of ssSSc compared to lcSSc [limited cutaneous SSc], while dcSSc [diffuse cutaneous SSc] remains the most severe disease form,” the authors wrote. “Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered,” they further added.

SOURCE:

The study was led by Anastasios Makris, MD, First Department of Propaedeutic & Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. It was published online on August 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The variability in the classification criteria across different studies may affect the comparability of results. The included studies lacked data on cardiac MRI, restricting the identification of myocardial fibrosis patterns and characterization of cardiac disease activity.

DISCLOSURES:

The study did not receive any specific funding. Some authors disclosed having a consultancy relationship, serving as speakers, and receiving funding for research from multiple companies. One author reported having a patent and being a cofounder of CITUS AG.

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:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

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:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

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:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

• GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
• Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
• They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
• The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
• The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

• The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
• Additionally, patients initiating DPP-4 inhibitors.
• In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

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.

CARLSBAD, CALIFORNIA — In 2003, researchers asked 303 patients with systemic sclerosis (scleroderma) what bothered them most about their disease from an aesthetic standpoint: Orofacial features, such as thin lips and mouth furrows, or non-facial features, such as fingertip ulceration and waxy changes to the skin.

Respondents expressed significant concern about specific orofacial features, including thin lips (73%), mouth furrows (80%), loss of facial lines (68%), and a smaller, tighter mouth (77%).

“Patients with systemic sclerosis may have loss of vermilion lip, microstomia, and perioral rhytids,” Kathleen Cook Suozzi, MD, who directs the Aesthetic Dermatology Program at Yale University School of Medicine, New Haven, Connecticut, said at the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium. “How can we address these changes for our patients?”

Yale University School of Medicine

Recent research has shown that hyaluronidase injections can help improve orofacial changes commonly experienced by patients with scleroderma. In 2019, researchers in Alabama reported the case of a 53-year-old woman treated with hyaluronidase for scleroderma-induced microstomia. After four visits over 7 months and a total hyaluronidase dose of 470 IU, the patient reported an improved Mouth Handicap in Systemic Sclerosis (MHISS) score (38 of 48); subjective improvement of symptoms, including greater ease in eating and undergoing dental treatment; and improved mouth closure.

In 2023, researchers published a cohort study of four women between the ages of 43 and 61 with autoimmune sclerosing conditions that resulted in oral microstomia. Following hyaluronidase injections, all improved in mouth opening capacity and MHISS, with change stabilizing between three and five treatments. More recently, in a study pending publication in JAAD Case Reports, Dr. Suozzi and colleagues retrospectively evaluated 12 women with scleroderma who received between 150 and 300 units of hyaluronic acid (HA) filler for microstomia between 2020 and 2023. Of the 12 women, 58% had diffuse disease, and 42% had limited disease. Overall, oral aperture width increased by 0.65 cm (P = .0027) and oral aperture height increased by 0.88 cm (P < .0001). “In general, patients needed three to four treatments to reach peak effect, and then they reached a plateau,” Dr. Suozzi said. “It wasn’t that the treatment wasn’t working anymore, but it was because their oral aperture had gotten to a size of around 5 cm, which is clinically normal. Interestingly, we found that if the patient’s disease flared and their microstomia started to return, when you rechallenged them, they continued to respond. So, patients can continue to use this treatment over time.”

In a separate case series of seven patients, Dr. Suozzi and colleagues prospectively evaluated the effect of HA soft tissue filler with Restylane Silk for lip augmentation. Study participants experienced statistically significant increases in the difference between pre- and postinjection fullness in both upper and lower lips. Also, the mean posttreatment score fell between “much improved” (2) and “improved” (3) on both the Investigator Global Aesthetic Improvement Scale and the Subject Global Aesthetic Improvement Scale.

Dr. Suozzi recommends using nerve blocks for injecting HA filler or hyaluronidase in patients with scleroderma and minimizing the injection points. “Initially, we were using 30% lidocaine preparations around the mouth for an hour before the procedure, and patients were still having pain, so now we use nerve blocks,” she said. “For hyaluronidase, we do perform a test dose of 75-100 units, usually in the commissure. It’s amazing how well it works; people will usually come back after their test dose and have improvements in their measurements. This is a really easy treatment to perform, and I think it can be done in the office of a general dermatologist. There is concern about cross-reactivity with bee venom, so you want to ask patients about that.”

Dr. Suozzi reported having no relevant financial relationships.
 

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

CARLSBAD, CALIFORNIA — In 2003, researchers asked 303 patients with systemic sclerosis (scleroderma) what bothered them most about their disease from an aesthetic standpoint: Orofacial features, such as thin lips and mouth furrows, or non-facial features, such as fingertip ulceration and waxy changes to the skin.

Respondents expressed significant concern about specific orofacial features, including thin lips (73%), mouth furrows (80%), loss of facial lines (68%), and a smaller, tighter mouth (77%).

“Patients with systemic sclerosis may have loss of vermilion lip, microstomia, and perioral rhytids,” Kathleen Cook Suozzi, MD, who directs the Aesthetic Dermatology Program at Yale University School of Medicine, New Haven, Connecticut, said at the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium. “How can we address these changes for our patients?”

Yale University School of Medicine

Recent research has shown that hyaluronidase injections can help improve orofacial changes commonly experienced by patients with scleroderma. In 2019, researchers in Alabama reported the case of a 53-year-old woman treated with hyaluronidase for scleroderma-induced microstomia. After four visits over 7 months and a total hyaluronidase dose of 470 IU, the patient reported an improved Mouth Handicap in Systemic Sclerosis (MHISS) score (38 of 48); subjective improvement of symptoms, including greater ease in eating and undergoing dental treatment; and improved mouth closure.

In 2023, researchers published a cohort study of four women between the ages of 43 and 61 with autoimmune sclerosing conditions that resulted in oral microstomia. Following hyaluronidase injections, all improved in mouth opening capacity and MHISS, with change stabilizing between three and five treatments. More recently, in a study pending publication in JAAD Case Reports, Dr. Suozzi and colleagues retrospectively evaluated 12 women with scleroderma who received between 150 and 300 units of hyaluronic acid (HA) filler for microstomia between 2020 and 2023. Of the 12 women, 58% had diffuse disease, and 42% had limited disease. Overall, oral aperture width increased by 0.65 cm (P = .0027) and oral aperture height increased by 0.88 cm (P < .0001). “In general, patients needed three to four treatments to reach peak effect, and then they reached a plateau,” Dr. Suozzi said. “It wasn’t that the treatment wasn’t working anymore, but it was because their oral aperture had gotten to a size of around 5 cm, which is clinically normal. Interestingly, we found that if the patient’s disease flared and their microstomia started to return, when you rechallenged them, they continued to respond. So, patients can continue to use this treatment over time.”

In a separate case series of seven patients, Dr. Suozzi and colleagues prospectively evaluated the effect of HA soft tissue filler with Restylane Silk for lip augmentation. Study participants experienced statistically significant increases in the difference between pre- and postinjection fullness in both upper and lower lips. Also, the mean posttreatment score fell between “much improved” (2) and “improved” (3) on both the Investigator Global Aesthetic Improvement Scale and the Subject Global Aesthetic Improvement Scale.

Dr. Suozzi recommends using nerve blocks for injecting HA filler or hyaluronidase in patients with scleroderma and minimizing the injection points. “Initially, we were using 30% lidocaine preparations around the mouth for an hour before the procedure, and patients were still having pain, so now we use nerve blocks,” she said. “For hyaluronidase, we do perform a test dose of 75-100 units, usually in the commissure. It’s amazing how well it works; people will usually come back after their test dose and have improvements in their measurements. This is a really easy treatment to perform, and I think it can be done in the office of a general dermatologist. There is concern about cross-reactivity with bee venom, so you want to ask patients about that.”

Dr. Suozzi reported having no relevant financial relationships.
 

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

CARLSBAD, CALIFORNIA — In 2003, researchers asked 303 patients with systemic sclerosis (scleroderma) what bothered them most about their disease from an aesthetic standpoint: Orofacial features, such as thin lips and mouth furrows, or non-facial features, such as fingertip ulceration and waxy changes to the skin.

Respondents expressed significant concern about specific orofacial features, including thin lips (73%), mouth furrows (80%), loss of facial lines (68%), and a smaller, tighter mouth (77%).

“Patients with systemic sclerosis may have loss of vermilion lip, microstomia, and perioral rhytids,” Kathleen Cook Suozzi, MD, who directs the Aesthetic Dermatology Program at Yale University School of Medicine, New Haven, Connecticut, said at the Controversies and Conversations in Laser and Cosmetic Surgery annual symposium. “How can we address these changes for our patients?”

Yale University School of Medicine

Recent research has shown that hyaluronidase injections can help improve orofacial changes commonly experienced by patients with scleroderma. In 2019, researchers in Alabama reported the case of a 53-year-old woman treated with hyaluronidase for scleroderma-induced microstomia. After four visits over 7 months and a total hyaluronidase dose of 470 IU, the patient reported an improved Mouth Handicap in Systemic Sclerosis (MHISS) score (38 of 48); subjective improvement of symptoms, including greater ease in eating and undergoing dental treatment; and improved mouth closure.

In 2023, researchers published a cohort study of four women between the ages of 43 and 61 with autoimmune sclerosing conditions that resulted in oral microstomia. Following hyaluronidase injections, all improved in mouth opening capacity and MHISS, with change stabilizing between three and five treatments. More recently, in a study pending publication in JAAD Case Reports, Dr. Suozzi and colleagues retrospectively evaluated 12 women with scleroderma who received between 150 and 300 units of hyaluronic acid (HA) filler for microstomia between 2020 and 2023. Of the 12 women, 58% had diffuse disease, and 42% had limited disease. Overall, oral aperture width increased by 0.65 cm (P = .0027) and oral aperture height increased by 0.88 cm (P < .0001). “In general, patients needed three to four treatments to reach peak effect, and then they reached a plateau,” Dr. Suozzi said. “It wasn’t that the treatment wasn’t working anymore, but it was because their oral aperture had gotten to a size of around 5 cm, which is clinically normal. Interestingly, we found that if the patient’s disease flared and their microstomia started to return, when you rechallenged them, they continued to respond. So, patients can continue to use this treatment over time.”

In a separate case series of seven patients, Dr. Suozzi and colleagues prospectively evaluated the effect of HA soft tissue filler with Restylane Silk for lip augmentation. Study participants experienced statistically significant increases in the difference between pre- and postinjection fullness in both upper and lower lips. Also, the mean posttreatment score fell between “much improved” (2) and “improved” (3) on both the Investigator Global Aesthetic Improvement Scale and the Subject Global Aesthetic Improvement Scale.

Dr. Suozzi recommends using nerve blocks for injecting HA filler or hyaluronidase in patients with scleroderma and minimizing the injection points. “Initially, we were using 30% lidocaine preparations around the mouth for an hour before the procedure, and patients were still having pain, so now we use nerve blocks,” she said. “For hyaluronidase, we do perform a test dose of 75-100 units, usually in the commissure. It’s amazing how well it works; people will usually come back after their test dose and have improvements in their measurements. This is a really easy treatment to perform, and I think it can be done in the office of a general dermatologist. There is concern about cross-reactivity with bee venom, so you want to ask patients about that.”

Dr. Suozzi reported having no relevant financial relationships.
 

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

TOPLINE:

The first year after the diagnosis of systemic lupus erythematosus (SLE) is crucial, with the highest percentage of patients experiencing organ damage. Cardiovascular issues are the second most prevalent after musculoskeletal damage in both early and later stages of SLE.

METHODOLOGY:

• Researchers assessed organ damage persisting at least 6 months over different stages of lupus in 4219 patients with SLE (mean age, 35.9 years; 89.6% women) from the Spanish Society of Rheumatology Lupus Registry.
• Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).
• Longitudinal analysis was conducted globally and by each SDI domain on 1274 patients with recorded damage event dates.
• Follow-up data were available out to 10 years in 1113 patients and to 20 years in 601.

TAKEAWAY:

• New damage was recorded in 20% of the patients with SLE within the first year after diagnosis, with the annual percentage of patients with new damage decreasing to 5% after the first 5 years of follow-up.
• In the first year, musculoskeletal damage was reported by the highest proportion of patients (21%), followed by cardiovascular damage inclusive of cerebrovascular accidents and claudication for 6 months (19%).
• The cardiovascular system remained the second most affected system even during the later stages of the diseases at years 10 and 20 of follow-up (20%-25%).
• Apart from musculoskeletal and cardiovascular damage, patients with lupus also showed renal and ocular damage in the early and later stages of the disease, respectively.

IN PRACTICE:

“Our study highlights the importance of cardiovascular damage and the need for its prevention during the earliest stages of the disease,” the authors wrote.

SOURCE:

The study was led by Irene Altabás-González, MD, PhD, Rheumatology Department, Vigo University Hospital Group, Vigo, Spain. It was published online in Lupus Science & Medicine.

LIMITATIONS:

The retrospective collection of data in the study may have led to missing items; for example, the dates of damage events for the whole cohort were not available. 

DISCLOSURES:

The registry was supported by the Spanish Society of Rheumatology. No specific funding was received for the study. 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 first year after the diagnosis of systemic lupus erythematosus (SLE) is crucial, with the highest percentage of patients experiencing organ damage. Cardiovascular issues are the second most prevalent after musculoskeletal damage in both early and later stages of SLE.

METHODOLOGY:

• Researchers assessed organ damage persisting at least 6 months over different stages of lupus in 4219 patients with SLE (mean age, 35.9 years; 89.6% women) from the Spanish Society of Rheumatology Lupus Registry.
• Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).
• Longitudinal analysis was conducted globally and by each SDI domain on 1274 patients with recorded damage event dates.
• Follow-up data were available out to 10 years in 1113 patients and to 20 years in 601.

TAKEAWAY:

• New damage was recorded in 20% of the patients with SLE within the first year after diagnosis, with the annual percentage of patients with new damage decreasing to 5% after the first 5 years of follow-up.
• In the first year, musculoskeletal damage was reported by the highest proportion of patients (21%), followed by cardiovascular damage inclusive of cerebrovascular accidents and claudication for 6 months (19%).
• The cardiovascular system remained the second most affected system even during the later stages of the diseases at years 10 and 20 of follow-up (20%-25%).
• Apart from musculoskeletal and cardiovascular damage, patients with lupus also showed renal and ocular damage in the early and later stages of the disease, respectively.

IN PRACTICE:

“Our study highlights the importance of cardiovascular damage and the need for its prevention during the earliest stages of the disease,” the authors wrote.

SOURCE:

The study was led by Irene Altabás-González, MD, PhD, Rheumatology Department, Vigo University Hospital Group, Vigo, Spain. It was published online in Lupus Science & Medicine.

LIMITATIONS:

The retrospective collection of data in the study may have led to missing items; for example, the dates of damage events for the whole cohort were not available. 

DISCLOSURES:

The registry was supported by the Spanish Society of Rheumatology. No specific funding was received for the study. 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 first year after the diagnosis of systemic lupus erythematosus (SLE) is crucial, with the highest percentage of patients experiencing organ damage. Cardiovascular issues are the second most prevalent after musculoskeletal damage in both early and later stages of SLE.

METHODOLOGY:

• Researchers assessed organ damage persisting at least 6 months over different stages of lupus in 4219 patients with SLE (mean age, 35.9 years; 89.6% women) from the Spanish Society of Rheumatology Lupus Registry.
• Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).
• Longitudinal analysis was conducted globally and by each SDI domain on 1274 patients with recorded damage event dates.
• Follow-up data were available out to 10 years in 1113 patients and to 20 years in 601.

TAKEAWAY:

• New damage was recorded in 20% of the patients with SLE within the first year after diagnosis, with the annual percentage of patients with new damage decreasing to 5% after the first 5 years of follow-up.
• In the first year, musculoskeletal damage was reported by the highest proportion of patients (21%), followed by cardiovascular damage inclusive of cerebrovascular accidents and claudication for 6 months (19%).
• The cardiovascular system remained the second most affected system even during the later stages of the diseases at years 10 and 20 of follow-up (20%-25%).
• Apart from musculoskeletal and cardiovascular damage, patients with lupus also showed renal and ocular damage in the early and later stages of the disease, respectively.

IN PRACTICE:

“Our study highlights the importance of cardiovascular damage and the need for its prevention during the earliest stages of the disease,” the authors wrote.

SOURCE:

The study was led by Irene Altabás-González, MD, PhD, Rheumatology Department, Vigo University Hospital Group, Vigo, Spain. It was published online in Lupus Science & Medicine.

LIMITATIONS:

The retrospective collection of data in the study may have led to missing items; for example, the dates of damage events for the whole cohort were not available. 

DISCLOSURES:

The registry was supported by the Spanish Society of Rheumatology. No specific funding was received for the study. 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.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

To the Editor:

Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory skin disease affecting 1% to 4% of Europeans. It is characterized by recurrent inflamed nodules, abscesses, and sinus tracts in intertriginous regions.¹ The genital area is affected in 11% of cases² and usually is connected to severe forms of HS in both men and women.³ The prevalence of HS-associated genital lymphedema remains unknown.

Saxophone penis is a specific penile malformation characterized by a saxophone shape due to inflammation of the major penile lymphatic vessels that cause fibrosis of the surrounding connective tissue. Poor blood flow further causes contracture and distortion of the penile axis.⁴ Saxophone penis also has been associated with primary lymphedema, lymphogranuloma venereum, filariasis,⁵ and administration of paraffin injections.⁶ We describe 3 men with HS who presented with saxophone penis.

A 33-year-old man with Hurley stage III HS presented with a medical history of groin lesions and progressive penoscrotal edema of 13 years’ duration. He had a body mass index (BMI) of 37, no family history of HS or comorbidities, and a 15-year history of smoking 20 cigarettes per day. After repeated surgical drainage of the HS lesions as well as antibiotic treatment with clindamycin 600 mg/d and rifampicin 600 mg/d, the patient was kept on a maintenance therapy with adalimumab 40 mg/wk. Due to lack of response, treatment was discontinued at week 16. Clindamycin and ­rifampicin 300 mg were immediately reintroduced with no benefit on the genital lesions. The patient underwent genital reconstruction, including penile degloving, scrotoplasty, infrapubic fat pad removal, and perineoplasty (Figure 1). The patient currently is not undergoing any therapies.

A 55-year-old man presented with Hurley stage II HS of 33 years’ duration. He had a BMI of 52; a history of hypertension, hyperuricemia, severe hip and knee osteoarthritis, and orchiopexy in childhood; a smoking history of 40 cigarettes per day; and an alcohol consumption history of 200 mL per day since 18 years of age. He had radical excision of axillary lesions 8 years prior. One year later, he was treated with concomitant clindamycin and rifampicin 300 mg twice daily for 3 months with no desirable effects. Adalimumab 40 mg/wk was initiated. After 12 weeks of treatment, he experienced 80% improvement in all areas except the genital region. He continued adalimumab for 3 years with good clinical response in all HS-affected sites except the genital region.

A 66-year-old man presented with Hurley stage III HS of 37 years’ duration. He had a smoking history of 10 cigarettes per day for 30 years, a BMI of 24.6, and a medical history of long-standing hypertension and hypothyroidism. A 3-month course of clindamycin and rifampicin 600 mg/d was ineffective; adalimumab 40 mg/wk was initiated. All affected areas improved, except for the saxophone penis. He continues his fifth year of therapy with adalimumab (Figure 2).

Hidradenitis suppurativa is associated with chronic pain, purulent malodor, and scarring with structural deformity. Repetitive inflammation causes fibrosis, scar formation, and soft-tissue destruction of lymphatic vessels, leading to lymphedema; primary lymphedema of the genitals in men has been reported to result in a saxophone penis.⁴

The only approved biologic treatments for moderate to severe HS are the tumor necrosis factor α inhibitor adalimumab and anti-IL-17 secukinumab.¹ All 3 of our patients with HS were treated with adalimumab with reasonable success; however, the penile condition remained refractory, which we speculate may be due to adalimumab’s ability to control only active inflammatory lesions but not scars or fibrotic tissue.⁷ Higher adalimumab dosages were unlikely to be beneficial for their penile condition; some improvements have been reported following fluoroquinolone therapy. To our knowledge, there is no effective medical treatment for saxophone penis. However, surgery showed good results in one of our patients. Among our 3 adalimumab-treated patients, only 1 patient had corrective surgery that resulted in improvement in the penile deformity, further confirming adalimumab’s limited role in genital lymphedema.⁷ Extensive resection of the lymphedematous tissue, scrotoplasty, and Charles procedure are treatment options.⁸

Genital lymphedema has been associated with lymphangiectasia, lymphangioma circumscriptum, infections, and neoplasms such as lymphangiosarcoma and squamous cell carcinoma.⁹ Our patients reported discomfort, hygiene issues, and swelling. One patient reported micturition, and 2 patients reported sexual dysfunction.

Saxophone penis remains a disabling sequela of HS. Early diagnosis and treatment of HS may help prevent development of this condition.

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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

VIENNA — It may have been a while since there have been any major breakthroughs in the treatment of systemic lupus erythematosus (SLE), but there are high hopes that this is a situation that may be about to change, experts agreed at the annual European Congress of Rheumatology.

“It’s an incredibly vivid area of development,” Laurent Arnaud, MD, PhD, professor of rheumatology at the University of Strasbourg in Strasbourg, France, said during one of the first sessions of the meeting. He reported that there were at least 17 phase 2 and 14 phase 3 trials that were expected to start within the next few years, all with investigational agents that target different immune cells or pathways that have been implicated in the pathogenesis of SLE.

Sara Freeman/Medscape Medical News

In a systematic review published last year, Dr. Arnaud and coauthors found that there were 92 investigational biologic or novel targeted agents in various phases of clinical testing. This included B-cell–targeting agents such as ianalumab, plasma cell-targeting agents such as daratumumab, and drugs with novel mechanisms of action such as KPG-818, which targets the CRL4-Cereblon (CRBN) E3 ubiquitin ligase complex. Phase 2 data on all three of these investigational agents were presented during various sessions at EULAR 2024, all with positive results, suggesting that their further development in SLE is worth pursuing.

There are of course “many more candidates in the pipeline,” Dr. Arnaud said. “I’m very happy that I think we are going to see great days for lupus right in front of our eyes.”
 

Targeting B Cells

Drugs that target B cells have been at the forefront of lupus treatment for several years, as David Isenberg, MD, professor of rheumatology at University College London, pointed out during an interview for EULAR TV.

“It’s clearly important to target the cells which are likely to be causing the problem in lupus, and in the main, that tends to be B cells,” he said.

Dr. Isenberg, who is renowned for his work with the B-cell–targeting agent rituximab, added: “But we know that obviously T cells integrate with B cells, so anything which interrupts the link between the T cell and the B cell is likely to be important.”
 

Chimeric Antigen Receptor (CAR) T-Cell Therapy ‘Revolution’

One new way of targeting B cells is with CAR T-cell therapy, which David D’Cruz , MD, PhD, a consultant rheumatologist for Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London, picked as one of the “most striking” topics highlighted at EULAR 2024.

This is “truly personalized medicine,” Dr. D’Cruz said. This is an autologous therapy because a patient’s T cells are removed by leukapheresis, transfected with a CAR T vector directed against a component of the B cell, and then returned to them.

“I do feel that we’re on the cusp of a major revolution,” Dr. D’Cruz told this news organization. Not only in lupus but also in other rheumatic conditions that have proved really difficult to treat, such as systemic sclerosis and myositis, he said.

“Basically, it’s a very powerful B-cell–depleting tool, but it’s much more profound B-cell–depleting tool than, for example, rituximab or belimumab,” explained Dr. D’Cruz. “What you’re doing is reprogramming T cells to attack the B cells.”

Although rituximab and belimumab clear all the B cells in the circulation, there are still some cells left behind in the bone marrow, “and it’s very difficult to get rid of those,” Dr. D’Cruz said. “What CAR T-cell therapy appears to do is wipe out all the CD19-positive B cells everywhere, in the blood and the tissue. So you get a really profound B-cell depletion.”

Eric Morand, MBBS, PhD, head of rheumatology at Monash Health in Melbourne, Australia, told this news organization that there was obviously “a lot of buzz” about CAR T-cell therapy.

Sara Freeman/Medscape Medical News

“We’re waiting to see if the exciting data from Erlangen can be reproduced in other centers with other CAR T products to show that it is a universal effect. We haven’t seen that yet, but I think we will by next year.”

Cost and expertise are two major considerations and potential limiting factors, however, as Dr. D’Cruz and Dr. Isenberg both pointed out in separate interviews with this news organization.

Dr. D’Cruz said: “It’s very expensive, it takes a while, and it doesn’t always work is what I’m hearing. It’s usually successful, but again, a little bit depends on the technique and the people doing the process.”

Dr. Isenberg said: “CAR T-cell therapy is, I think, very exciting because it does look to be quite promising. But as it costs 350,000 euros per patient, I don’t think that it is going to be widely adopted.”

Even if it could be afforded by certain centers in the West, he added, this just would not be feasible in poorer nations. “So, we’ve got to find other effective, cheaper ways to go,” Dr. Isenberg said.

“I think there are some very interesting ideas with monoclonal antibodies which target at least two different targets — one on the B cell, one on the T cell — and that could well be the way to take this forward,” he suggested.
 

Ianalumab ‘Double Blocking’ B Cells

Another way could be to develop more potent B-cell–depleting drugs, as Nancy Agmon-Levin , MD, head of the Clinical Immunology, Angioedema and Allergy Unit, Lupus and Autoimmune Diseases Clinic, at Sheba Medical Center, Tel Aviv University in Tel Aviv, Israel, reported during one of the clinical abstract sessions at EULAR 2024.

Dr. Agmon-Levin presented data on 67 individuals with SLE who had participated in a multicenter phase 2 study of ianalumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that results in a “double blocking of the B-cell lineage.”

Ianalumab targets the B-cell–activating factor receptor (BAFFR), but what makes it distinct from other BAFF-targeting drugs is that it has had a fructose molecule removed from its Fc portion, which renders it more likely to trigger antibody-dependent cellular cytotoxicity.

“This is a B-cell depletion therapy,” Agmon-Levin said, but it also blocks BAFFR-mediated survival of B cells, so the subsequent recuperation process of BAFFR-expressing B cells is affected, leading to continued B-cell depletion.

The phase 2 study she presented consisted of an initial 28-week, double-blind period, during which time participants had been randomly allocated to receive either subcutaneous injections of ianalumab 300 mg or a matching placebo every 4 weeks. This was followed by a 24-week, open-label period where all participants were treated with ianalumab, and then an off-treatment, minimal follow-up period that lasted up to 68 weeks, with continued data collection for safety.

The primary outcome measure was a composite of meeting criteria for the SLE Responder Index 4 and a sustained reduction in corticosteroid use at 28 weeks. This was achieved in 15 of the 34 (44.1%) people treated with ianalumab vs only 3 (9.1%) of the 33 people who had been given a placebo.

Dr. Agmon-Levin reported that the effect on this outcome was sustained to the end of the open-label period, at 1 year, in 15 (45.5%) of 33 participants who had continued treatment with ianalumab and achieved in 13 (40.6%) of 32 participants who had switched from placebo to ianalumab treatment.

Moreover, longer durations of treatment were associated with a host of improved outcomes, Dr. Agmon-Levin said: “Treatment was improved along the 52 weeks, and we can see from the LLDAS [Lupus Low Disease Activity State], DORIS [Definition Of Remission In SLE], and SRI-6 and -8 that as you continue the therapy, you improve the outcomes.”

The potential benefits of ianalumab in the treatment of SLE and lupus nephritis will now be further examined in the phase 3 SIRIUS-SLE1 , SIRIUS-SLE2, and SIRIUS-LN trials, which are estimated to provide initial results in 2027 and complete in early 2029 or 2030.
 

Targeting Plasma Cells With Daratumumab

Another drug showing signs that it might be useful as a treatment for SLE is daratumumab, as Tobias Alexander, MD, of Charité — Universitätsmedizin Berlin, reported during one of the late-breaking abstract sessions at EULAR 2024.

“Daratumumab is a human, first-in-class anti-CD38 antibody that efficiently depletes plasma cells,” Dr. Alexander said. CD38 is both a receptor and an enzyme, and while it is found on the surface of most immune cells, it’s particularly expressed by plasma cells, he added.

Daratumumab is not a total newcomer, however, as it’s already approved for the treatment of multiple myeloma under the trade name Darzalex. The rationale for using it in SLE comes from two case reports, Dr. Alexander explained. The first, published in 2020 in The New England Journal of Medicine, involved two patients with severe and life-threatening lupus who were given off-label treatment for a period of 4 weeks and experienced good clinical and serologic responses. The second, published last year in Nature Medicine, involved six patients with refractory lupus nephritis, five of whom had a clinical response at 6 months.

“On this background, we conducted an investigator-initiated trial, which was an open-label, single-center, proof-of-concept study,” Dr. Alexander said. A total of 10 female patients whose ages ranged from 24 to 43 years were included in the phase 2 trial that was dubbed DARALUP. For inclusion, all had to have a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of four or more for clinical manifestations, have been treated with at least two prior disease-modifying drugs to no avail, and be anti–double-stranded DNA (anti-dsDNA) antibody positive. Dr. Alexander reported that the median baseline SLEDAI-2K score was 12 and ranged from 8 to 20, with the number of prior therapies ranging from two to nine.

Daratumumab was given at a dose of 1800 mg via subcutaneous injection every week for 8 weeks. This is the same dose that is used to treat multiple myeloma, Dr. Alexander explained, although the dosing is not stopped. The reason for stopping after 8 weeks in the current trial was to be able to see what happened once the treatment was stopped. The follow-up was for 36 weeks.

Dr. Alexander reported that there was a “very dramatic and significant” effect on the primary endpoint of a reduction in anti-dsDNA antibody levels, decreasing from a median of 166.3 U/mL at baseline to 61.1 U/mL at week 12 (P = .002). Alongside, there was a reduction in the SLEDAI-2K score from 12 to 4 within 12 weeks, which was sustained at the 36-week follow-up assessment. Improvements in skin, joint, kidney, and level of proteinuria were also seen.

Although all patients experienced adverse events, none were serious. Infections and infestations (mostly nasopharyngitis, COVID-19, and gastroenteritis) were the most common, experienced by 80% of the participants; 70% had injection site reactions or fatigue, 60% had gastrointestinal symptoms, 50% had a fall of IgG < 5 g/L, 40% had headache, and 20% had back pain.

“This is a positive trial. I think we could demonstrate that [daratumumab] produced very strong, rapid, and durable clinical improvements,” Dr. Alexander said. “We think that targeting CD38 is relevant; plasma cells had been depleted based on the reduction of anti-dsDNA antibodies,” he added.

From the audience, however, Peter Nash, MBBS, of Griffith University in Brisbane, Australia, questioned whether the results could be attributed to “a steroid effect” because patients had been treated with oral dexamethasone throughout the study.

Dr. Alexander noted that steroid use had been part of the treatment schedule but acknowledged it was a possible confounder.

“I think we can be confident that [daratumumab] had a major effect on plasma cells decreasing…because we see that also the vaccine titers decreased,” Dr. Alexander said. “Time will tell, but even more important is the durability of the responses over time, which you don’t achieve under steroids.”
 

KPG-818’s Novel Mechanism of Action

Elsewhere at EULAR 2024, positive results of another phase 2 study involving a drug with an entirely different mechanism of action, KPG-818, were reported in a poster presentation. KPG-818 modulates CRBN, which results in the degradation of two transcription factors (Aiolos and Ikaros) that are involved in the development, maturation, and proliferation of innate and adaptive immune cells and have been linked to genetic risk in SLE, according to the poster’s authors. It is currently in development for the treatment of SLE, Behçet disease, inflammatory bowel disease, multiple myeloma, and non-Hodgkin lymphoma.

Yao Wang, MD, chief medical officer of KPG-818’s developer Kangpu Biopharmaceuticals, Hefei, China, and associates found that oral doses of 0.15 or 0.6 mg KPG-818 were “generally well-tolerated” and produced immunomodulatory changes that could be beneficial in people with SLE over a 12-week treatment period.

“Only two new agents have been approved for the treatment of SLE in the past five decades in USA and Europe,” Dr. Wang and team wrote, which highlights “a significant unmet need for more effective and safe treatment options.”

They believe that KPG-818 might well fit the bill based on the results of their study, in which 35 of 37 recruited patients completed the treatment. Compared with placebo, they observed reduced numbers of total B cells, Aiolos+ T and B cells, and increased Treg cells.

SLEDAI-2K and Cutaneous Lupus Erythematosus Disease Area and Severity Index activity scores in the 0.15-mg group were improved relative to baseline and placebo.

“The proof-of-concept findings suggest a favorable benefit/risk ratio in SLE for KPG-818,” Dr. Wang and coauthors said, supporting its further development in SLE.
 

Need for Treatments

Dr. Isenberg told this news organization that both daratumumab and KPG-818 would be welcome additions as treatment options if further trials proved their worth.

“The great frustration about lupus is that, compared to patients with rheumatoid arthritis, the choice has been so limited,” Dr. Isenberg said. Aside from rituximab (Rituxan) and belimumab (Benlysta), which are used with certain restrictions, there are no other biologic targeted treatments available in the United Kingdom. Anifrolumab (Saphnelo) has a license in the United States and some European countries but is not yet available for him to use in his practice.

Daratumumab and KPG-818 are “different types of molecules, and if they work that will be great. It would be nice to have the choice,” Dr. Isenberg said. “Whether they will be as effective as I think rituximab is, I don’t know, but these are some very encouraging results.”

Of course, these are all phase 2 trials, and the “big problem” is that such positive results do not always translate when it comes to phase 3, as Dr. D’Cruz told this news organization.

“Until a few years ago, there had been about 25 or 30 industry-led trails, and they’d all failed, except for belimumab and anifrolumab,” Dr. D’Cruz said. These drugs were found to work and be generally safe in phase 1 and 2 trials, but “when they come to phase 3, they all seem to fail, and we don’t know why.”

These are large global studies, D’Cruz added, observing that problems with patient selection, steroid use, and choice of outcome measures were possible factors for why the EXPLORER and LUNAR studies had shown no benefit for rituximab despite the drug being widely used to treat SLE.

Dr. Isenberg, who has coauthored an article on the topic of why drugs seem to fail at the final hurdle, noted: “I think it has a lot to do with the nature of the disease. It’s a complicated disease.” From having “savvy physicians doing the trials for you” to the placebo response, there are “a whole bunch or reasons why these things haven’t worked in lupus.”

Dr. Morand commented: “We’ve got many programs in phase 2 and 3, and because there’s so many, they’re all facing recruitment challenges, and as a consequence of so much activity, every program is going a little slower than hoped for.”

As for other drugs on the horizon, Dr. Morand noted: “We’re very optimistic about things like litifilimab and deucravacitinib; that’s two examples that are in phase 3. Earlier in the program of development, [there are] a huge range of targets being addressed. The future looks bright. But we might have to wait a while.”

Dr. Arnaud has consulted for AstraZeneca, AbbVie, Alpine Immune Sciences, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, GlaxoSmithKline, Grifols, Janssen, Kezar Life Sciences, LFB, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Dr. Isenberg has served as an adviser to Merck Serono, AstraZeneca, Eli Lilly, Servier, and ImmuPharma. Any honoraria received is passed on to a local arthritis charity connected to his hospital. Dr. D’Cruz has served as a consultant and advisory board member for GlaxoSmithKline and CSL Vifor. Dr. Morand has received research support, consultancy fees, or both from multiple pharmaceutical companies paid to his institution including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Dragonfly, Genentech, GlaxoSmithKline, Janssen, Novartis, RemeGen, Takeda, UCB, and Zenas. The ianalumab trial presented by Dr. Agmon-Levin was sponsored by Novartis Pharma; however, she reported having no conflicts of interest. The DARALUP study was an investigator-initiated trial supported by Janssen. Dr. Alexander has received consulting fees, study support, honoraria, and travel grants from various pharmaceutical companies including AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, and Lilly. Dr. Nash has consulted for The Rheumatology Education Group Consultants. The KPG-818 study reported by Dr. Wang was sponsored by Kangpu Biopharmaceuticals.
 

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